Immunology Graduate Program

Visit the Alenghat Lab.

BS: Brown University, Providence, RI, 1999.

VMD: University of Pennsylvania, Philadelphia, PA, 2003.

PhD: University of Pennsylvania, Philadelphia, PA, 2007.

Residency: Anatomic Pathology, University of Pennsylvania, Philadelphia, PA.

Certification: Diplomate ACVP, 2011.

Whitsett J, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nature Immunology. 2015;16:27-35.

Giacomin PG, Moy RH, Noti M, Osborne LC, Siracusa MC, Alenghat T, Liu B, McCorkell KA, Troy AE, Rak GD, Hu Y, May MJ, Ma H, Fouser LA, Sonnenberg GF, Artis D. Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity. J Exp Med. 2015;212:1513-28.

Tait Wojno ED, Monticelli LA, Tran SV, Alenghat T, Osborne LC, Thome JJ, Willis C, Budelsky A, Farber DL, Artis D. The prostaglandin D2 receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol. 2015 Nov;8(6):1313-23.

Alenghat T, Artis D. Epigenomic regulation of host-microbiota interactions. Trends in Immunology. 2014;35:518-525.

Alenghat T, Osborne LC, Saenz SA, Kobuley D, Ziegler CG, Mullican SE, Choi I, Grunberg S, Sinha R, Wynosky-Dolfi M, Snyder A, Giacomin PG, Joyce KL, Hoang TB, Bewtra M, Brodsky IE, Sonnenberg GF, Bushman FD, Won K, Lazar MA, Artis D. Histone Deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature. 2013 Dec 5;504(7478):153-7.

Abt MC, Osborne LC, Monticelli LA, Doering T, Alenghat T, Sonnenberg GF, Paley MA, Antenus M, Williams KL, Erikson J, Wherry EJ, Artis D. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity. 2012 Jul 27;37(1):158-70.

Sonnenberg GF, Monticelli LA, Alenghat T, Fung TC, Hutnick NA, Kunisawa J, Shibata N, Grunberg S, Sinha R, Zahm AM, Tardif MR, Sathaliyawala T, Kubota M, Farber DL, Collman RG, Shaked A, Fouser LA, Weiner DB, Tessier PA, Friedman JR, Kiyono H, Bushman FD, Chang K, Artis D. Innate lymphoid cells orchestrate anatomical containment of lymphoid-resident commensal bacteria and prevent systemic immune activation. Science. 2012 Jun 8;336(6086): 1321-5.

Monticelli LA, Sonnenberg GF, Abt MC, Alenghat T, Ziegler CG, Doering TA, Angelosanto JM, Laidlaw BJ, Yang CY, Sathaliyawala T, Kubota M, Turner D, Diamond JM, Goldrath AW, Farber DL, Collman RG, Wherry EJ, Artis D. Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus. Nat Immunol. 2011 Nov;12(11):1045-54.

Feng D, Liu T, Sun Z, Bugge A, Mullican SE, Alenghat T, Liu XS, Lazar MA. A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism. Science. 2011 Mar 11;331(6022):1315-9.

Alenghat T, Meyers K, Mullican SE, Leitner K, Adeniji-Adele A, Avila J, Bućan M, Ahima RS, Kaestner KH, Lazar MA. Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology. Nature. 2008 Dec 18;456(7224): 997-1000.

Artem Barski, PhD

uses cutting-edge genomic technologies (such as ChIP-Seq and RNA-Seq) to understand contribution of epigenetic mechanisms and polymerase stalling to T cell activation, differentiation and to formation of T cell memory.
Visit the Barski Lab.

513-636-1851 artem.barski@cchmc.org

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Artem Barski, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-1851

Email artem.barski@cchmc.org

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Epigenetics; epigenomics; immunology; T cell memory

Visit the Barski Lab.

Biography

Artem Barski, PhD, is interested in epigenetic and transcriptional regulation of gene expression. During his post-doctoral training in Keji Zhao lab at NIH, Dr. Barski took part in the development of ChIP-Seq, a revolutionary method that combines ChIP with the next-generation sequencing. ChIP-Seq allows genome-wide mapping of chromatin modifications and transcription factor binding sites with resolution and sensitivity far exceeding older methods. Together with his NIH colleagues Dr. Barski used this approach to map more than 40 chromatin modifications in human T cells, which fundamentally improved the understanding of epigenetic regulation of transcription. Dr. Barski has since been using ChIP-Seq and other sequencing-based genome-wide methods to understand the role of chromatin modifications in gene regulation. His most recent work includes investigation of chromatin regulation of genes transcribed by RNA Polymerase III and the discovery of gene poising in T cells.

Since his arrival to Cincinnati Children’s Hospital Medical Center in 2011, Dr. Barski is utilizing ChIP-Seq, RNA-Seq and other cutting-edge approaches to understand epigenetic basis of T cell activation, memory and tolerance.

BS/MS: Moscow State University, Department of Chemistry, Moscow, Russia, 2000.

PhD: University of Southern California, Los Angeles, CA, 2006.

Fellowship: National Institutes of Health (NIH), National Heart Lung, and Blood Institute (NHLBI), Bethesda, MD, 2011.

Barski A, Chepelev I, Liko D, Cuddapah S, Fleming AB, Birch J, Cui K, White RJ, Zhao K. Pol II and its associated epigenetic marks are present at Pol III-transcribed noncoding RNA genes. Nat Struct Mol Biol. 2010 May;17(5):629-34.

Cuddapah S, Barski A, Zhao K. Epigenomics of T cell activation, differentiation, and memory. Curr Opin Immunol. 2010 Jun;22(3):341-7.

Cuddapah S, Barski A, Cui K, Schones DE, Wang Z, Wei G, Zhao K. Native chromatin preparation and Illumina/Solexa library construction. Cold Spring Harb Protoc. 2009 Jun;2009(6):pdb.prot5237.

Barski A, Jothi R, Cuddapah S, Cui K, Roh TY, Schones DE, Zhao K. Chromatin poises miRNA- and protein-coding genes for expression. Genome Res. 2009 Oct;19(10):1742-51

Barski A, Zhao K. Genomic location analysis by ChIP-Seq. J Cell Biochem. 2009 May 1;107(1):11-8.

Jothi R, Cuddapah S, Barski A, Cui K, Zhao K. Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data. Nucleic Acids Res. 2008 Sep;36(16):5221-31.

Wang Z, Zang C, Rosenfeld JA, Schones DE, Barski A, Cuddapah S, Cui K, Roh TY, Peng W, Zhang MQ, Zhao K. Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet. 2008 Jul;40(7):897-903

Schones DE, Cui K, Cuddapah S, Roh TY, Barski A, Wang Z, Wei G, Zhao K. Dynamic regulation of nucleosome positioning in the human genome. Cell. 2008 Mar 7;132(5):887-98.

Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. High-resolution profiling of histone methylations in the human genome. Cell. 2007 May 18;129(4):823-37.

Barski A, Frenkel B. ChIP Display: novel method for identification of genomic targets of transcription factors. Nucleic Acids Res. 2004 Jul 13;32(12):e104.

Jorge A. Bezerra, MD Director, Division of Gastroenterology, Hepatology and Nutrition

investigates the genetic, cellular and molecular basis of biliary atresia and other cholangiopathies in children. His studies use animal models of disease to identify causes of tissue injury and to develop new therapies to stop progression of liver disease.
Visit the Bezerra Lab.

513-636-3008 jorge.bezerra@cchmc.org

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Jorge A. Bezerra, MD

Director, Division of Gastroenterology, Hepatology and Nutrition

Medical Director, Pediatric Liver Care Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3008

Fax 513-636-5581

Email jorge.bezerra@cchmc.org

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Visit the Bezerra Lab.

Biography

Jorge A. Bezerra, MD, joined the Cincinnati Children's Hospital Medical Center Division of Gastroenterology, Hepatology and Nutrition in 1990, when he began his fellowship training in pediatric gastroenterology and nutrition and graduated in 1993.

From 1992-1994, Dr. Bezerra was a research scholar in the Division of Basic Sciences. He was appointed to the division in 1994 as an assistant professor within the UC Department of Pediatrics.

Dr. Bezerra completed his residency in pediatrics at the University of Arizona in Tucson, Arizona.

Dr. Bezerra has an active research career with his primary interests in molecular control of liver regeneration, biliary atresia, and genetic basis of intrahepatic cholestasis.

In addition to his research work, Dr. Bezerra is an active clinician for the outpatient GI clinical service and the inpatient liver service.

MD: Federal University Rio Grande Norte, Natal, Brazil, 1984.

Residency: University of Arizona, Tuscon, AZ, 1989.

Fellowship: Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, 1994.

Certification: Pediatrics, Pediatric Gastroenterology, Hepatology and Nutrition.

Bezerra JA. Biliary atresia in Brazil: where we are and where we are going. J Pediatr (Rio J). 2010 Nov-Dec;86(6):445-7.

Moyer K, Kaimal V, Pacheco C, Mourya R, Xu H, Shivakumar P, Chakraborty R, Rao M, Magee JC, Bove K, Aronow BJ, Jegga AG, Bezerra JA. Staging of biliary atresia at diagnosis by molecular profiling of the liver. Genome Med. 2010 May 13;2(5):33.

Kumar Mohanty S, Ivantes CA, Mourya R, Pacheco C, Bezerra JA. Macrophages are targeted by rotavirus in experimental biliary atresia and induce neutrophil chemotaxis via Mip2/Cxcl2. Pediatr Res. 2010 Jan 6.

Shivakumar P, Sabla GE, Whitington P, Chougnet CA, Bezerra JA. Neonatal NK cells target the mouse duct epithelium via Nkg2d and drive tissue-specific injury in experimental biliary atresia. J Clin Invest. 2009 Aug;119(8):2281-90.

Shanmukhappa K, Matte U, Degen JL, Bezerra JA. Plasmin-mediated proteolysis is required for hepatocyte growth factor activation during liver repair. J Biol Chem. 2009 May 8;284(19):12917-23.

Erickson N, Mohanty SK, Shivakumar P, Sabla G, Chakraborty R, Bezerra JA. Temporal-spatial activation of apoptosis and epithelial injury in murine experimental biliary atresia. Hepatology. 2008 May;47(5):1567-77.

Shivakumar P, Sabla G, Mohanty S, McNeal M, Ward R, Stringer K, Caldwell C, Chougnet C, Bezerra JA. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007 Jul;133(1):268-77.

Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, Bezerra JA. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26.

Campbell KM, Arya G, Ryckman FC, Alonso M, Tiao G, Balistreri WF, Bezerra JA. High prevalence of alpha-1-antitrypsin heterozygosity in children with chronic liver disease. J Pediatr Gastroenterol Nutr. 2007 Jan;44(1):99-103.

Shanmukhappa K, Sabla GE, Degen JL, Bezerra JA. Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor. BMC Gastroenterol. 2006 Nov 29;6:40.

Charles C. Caldwell, PhD

focuses his research around trauma, sepsis and inflammation.

513-558-1974 caldwecs@ucmail.uc.edu

Jose A. Cancelas Perez, MD, PhD Division Director of Research, Hoxworth Blood Center

focuses on the study of blood-forming cells during the process of adult hematopoiesis. In particular, hematopoietic stem cells (HSC) attract clinical interest because of their potential use in stem cell and gene therapy, and because of their involvement in leukemia.
Visit the Cancelas Lab.

513-558-1324 jose.cancelas@uc.edu

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Jose A. Cancelas Perez, MD, PhD

Division Director of Research, Hoxworth Blood Center

Deputy Director, Hoxworth Blood Center

Director, Research Flow Cytometry Core

Leader, Stem Cell Program

Medical Director of Cellular Therapies, Hoxworth Blood Center

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-558-1324

Fax 513-558-1522

Email jose.cancelas@uc.edu

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Clinical

Hematopoietic stem cell proliferation and differentiation

Research

Visit the Cancelas Lab.

MD: Autonomous University of Madrid, Spain, 1989.

Residency: Hematology and Hematotherapy, University of Alcala de Henares, Madrid, Spain, 1993.

PhD: Faculty of Medicine, University of Alcala de Henares, Madrid, Spain, 1996.

Dumont LJ*, Cancelas JA*, Graminske S, Friedman KD, Vassallo RR, Whitley PH, Rugg N, Dumont DF, Herschel L, Siegal AH, Szczepiorkowski ZM, Fender L, Razatos A. In vitro and in vivo quality of leukocyte-reduced apheresis platelets stored in a new platelet additive solution. Transfusion. 2012. (*both authors contributed equally).

Prada CE, Jousma E, Rizvi TA, Wu J, Dunn RS, Mayes DA, Cancelas JA, Dombi E, Kim MO, West BL, Bollag G, Ratner N. Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition. Acta Neuropathol. 2013 Jan;125(1):159-68.

Dumont LJ, Cancelas J, Dumont DF, Siegel AH, Szczepiorkowski ZM, Rugg R, Pratt PG, Worsham DN, Hartman EL, Dunn SK, O’Leary M, Ransom JH, Michael RA, Macdonald VW. A randomized controlled trial evaluating recovery and survival of 6% dimethyl sulfoxide-frozen autologous platelets in healthy volunteers. Transfusion. 2013 Jan;53(1):128-37.

Taniguchi Ishikawa E, Cancelas JA. Lack of communication rusts and ages stem cells. Cell Cycle. 2012 Sep 1;11(17):3149-3150.

Geiger H, Pawar SA, Kerschen EJ, Nattamai KJ, Hernandez I, Liang HP, Fernández JA, Cancelas JA, Ryan MA, Kustikova O, Schambach A, Fu Q, Wang J, Fink LM, Petersen KU, Zhou D, Griffin JH, Baum C, Weiler H, Hauer-Jensen M. Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity. Nat Med. 2012 Jul;18(7):1123-9.

Chang KH, Sanchez-Aguilera A, Shen S, Sengupta A, Madhu MN, Ficker AM, Dunn SK, Kuenzi AM, Anrett JL, Santho RA, Agirre X, Perentesis JP, Deininger MW, Zheng Y, Bustelo XR, Williams DA, Cancelas JA. Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation and survival. Blood. 2012 Jul 26;120(4):800-11.

Taniguchi Ishikawa E, Gonzalez-Nieto D, Ghiaur G, Dunn SK, Ficker AM, Murali B, Madhu M, Gutstein DE, Fishman GI, Barrio LC, Cancelas JA. Connexin-43 prevents hematopoietic stem cell senescence through transfer of reactive oxygen species to bone marrow stromal cells. Proc Natl Acad Sci USA. 2012 Jun 5;109(23):9071-6.

Konstantinidis DG, Pushkaran S, Johnson JF, Cancelas JA, Manganaris S, Harris CE, Williams DA, Zheng Y, Kalfa TA. Signaling and cytoskeletal requirements in erythroblast enucleation. Blood. 2012 Jun 21;119(25):6118-27.

Gonzalez-Nieto D, Li L, Köhler A, Ghiaur G, Ishikawa E, Sengupta A, Madhu M, Arnett J, Santho R, Dunn S, Fishman G, Gutstein D, Civitelli R, Barrio L, Gunzer M, Cancelas J. Connexin-43 in the osteogenic BM niche regulates its cellular composition and the bidirectional traffic of hematopoietic stem cells and progenitors. Blood. 2012 May 31;119(22):5144-54.

Sengupta A, Ficker A, Dunn S, Madhu M, Cancelas JA. Bmi1 reprograms chronic myelogenous leukemia B-lymphoid progenitors to become B-ALL-initiating cells. Blood. 2012 Jan 12;119(2):494-502.

Grants

Progenitor Cell Biology Consortium Administrative Coordinating Center, NHLBI/ Subaward through Univ. Maryland. Co-Director. (Cincinnati Cell Char Core). Sep 2010 – Aug 2016. #U01 HL099997.

Claire A. Chougnet, PhD

aims to understand T cell function and dysfunction at a molecular level in human disease, with a focus on defining the molecular mechanisms that underlie T cell dysfunction in HIV/AIDS, defining the molecular mechanisms responsible for immune dysfunction in aging, and understanding the development of T cell responses in very early life.
Visit the Chougnet Lab.

513-636-8847 claire.chougnet@cchmc.org

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Claire A. Chougnet, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8847

Fax 513-636-4278

Email claire.chougnet@cchmc.org

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Visit the Chougnet Lab.

DPharm: Université Paris XI, Paris, France, 1980.

CES (French specialized degrees; clinical biologist): Immunology, Hematology, Bacteriology-Virology, Parasitology, 1984.

PhD: Université Paris V, 1991.

Lages CS, Lewkowich I, Sproles A, Wills-Karp M, Chougnet C. Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/ PD-L1 pathway. Aging Cell. 2010 Oct;9(5):785-98. doi: 10.1111/j.1474-9726.2010.00611.x.

Miethke AG, Saxena V, Shivakumar P, Sabla GE, Simmons J, Chougnet CA. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol. 2010 May;52(5):718-26.

Presicce P, Moreno-Fernandez ME, Lages CS, Orsborn KI, Chougnet CA. Association of two clones allows for optimal detection of human FOXP3. Cytometry A. 2010 Jun;77(6):571-9.

Moreno-Fernandez ME, Zapata W, Blackard JT, Franchini G, Chougnet CA. Human regulatory T cells are targets for human immunodeficiency Virus (HIV) infection, and their susceptibility differs depending on the HIV type 1 strain. J Virol. 2009 Dec;83(24):12925-33.

Shivakumar P, Sabla GE, Whitington P, Chougnet CA, Bezerra JA. Neonatal NK cells target the duct epithelium via Nkg2d and drive the tissue-specific injury in biliary atresia. J Clin Invest. 2009 Aug;119(8)2281-90.

Nyakeriga AM, Fichtenbaum CJ, Goebel J, Nicolaou SA, Conforti L, Chougnet CA. Engagement of the CD4 receptor affects the redistribution of lck to the immunological synapse in primary T cells: implications for T cell activation during HIV-1 infection. J Virol. 2009 Feb;83(3):1193-200.

Boasso A, Shearer GM, Chougnet C. Immune dysregulation in HIV infection: know it, fix it, prevent it? J Intern Med. 2009, 265(1):78-96. Review.

Lages CS, Suffia I, Velilla P, Huang B, Warshaw G, Hildeman D, Belkaid Y, Chougnet C. Functional regulatory T cells accumulate in aged hosts and promote reactivation of chronic infectious disease reactivation. J Immunol. 2008;181(3):1835-48.

Velilla PA, Shata MT, Lages CS, Ying J, Fichtenbaum CJ, Chougnet C. Effect of intrauterine HIV-1 exposure on the frequency and phenotype of uninfected newborns’ dendritic cells. Clin Immunol. 2008;126:243-50.

Li S, Gowans EJ, Chougnet C, Plebanski M, Dittmer U. Natural regulatory T cells and persistent viral infection. J Virol. 2008;82:21-30. Review.

George Deepe, MD

focuses on the analysis of the protective immune response to the pathogenic fungus, Histoplasma capsulatum. His lab endeavors to determine the influence of cytokines and T cell subpopulations on host control of fungus. Using a mouse model to examine lungs which are the portal of entry for this fungus, our current studies investigate the role of chemokines and their receptors in host control of this fungus.
Visit the Deepe Lab.

513-558-4704 george.deepe@uc.edu

George Deepe, MD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-558-4704

Email george.deepe@uc.edu

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Host response to fungi

AB: Kenyon College, English and Biology, 1971.

MD: University of Cincinnati College of Medicine, 1976.

Kroetz DN, Deepe GS Jr. An aberrant thymus in CCR5-/- mice is coupled with an enhanced adaptive immune response in fungal infection. J Immunol. 2011 May 15;186(10):5949-55.

Szymczak WA, Deepe GS Jr. Antigen-presenting dendritic cells rescue CD4-depleted CCR2-/- mice from lethal Histoplasma capsulatum infection. Infect Immun. 2010 May;78(5):2125-37.

Kroetz DN, Deepe GS Jr. CCR5 dictates the equilibrium of proinflammatory IL-17+ and regulatory Foxp3+ T cells in fungal infection. J Immunol. 2010 May 1;184(9):5224-31.

Szymczak WA, Deepe GS Jr. The CCL7-CCL2-CCR2 axis regulates IL-4 production in lungs and fungal immunity. J Immunol. 2009 Aug 1;183(3):1964-74.

McCormack FX, Gibbons R, Ward SR, Kuzmenko A, Wu H, Deepe GS Jr. Macrophage-independent fungicidal action of the pulmonary collectins. J Biol Chem. 2003 Sep 19;278(38):36250-6.

Gomez FJ, Woodward EO, Pilcher-Roberts R, Gibbons RS, Deepe GS Jr. V beta 6+ and V beta 4+ T cells exert cooperative activity in clearance of secondary infection with Histoplasma capsulatum. J Immunol. 2001 Feb 15;166(4):2855-62.

Allendoerfer R, Deepe GS Jr. Regulation of infection with Histoplasma capsulatum by TNFR1 and -2. J Immunol. 2000 Sep 1;165(5):2657-64.

Deepe GS Jr, Gibbons R, Woodward E. Neutralization of endogenous granulocyte-macrophage colony-stimulating factor subverts the protective immune response to Histoplasma capsulatum. J Immunol. 1999 Nov 1;163(9):4985-93.

Allendörfer R, Brunner GD, Deepe GS Jr. Complex requirements for nascent and memory immunity in pulmonary histoplasmosis. J Immunol. 1999 Jun 15;162(12):7389-96.

Gomez FJ, Cain, JA, Gibbons R, Allendoerfer R, and Deepe GS, Jr. Vβ4+T cells exert protection in murine in pulmonary histoplasmosis. J Clin Invest. 1998;102:984-995.

Senad Divanovic, PhD

investigates the molecular mechanisms underlying the regulation of innate immune signaling and inflammation in: (a) development and progression of obesity; (b) development and progression of non-alcoholic fatty liver disease; and (b) induction of preterm birth. These studies, range from reductive analysis of TLR ligand signaling and challenge to the role of IL-17 axis to diverse experimental models of obesity and infection.
Visit the Divanovic Lab.

513-636-0286 senad.divanovic@cchmc.org

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Senad Divanovic, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-0286

Email senad.divanovic@cchmc.org

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Clinical Interests

Innate immune responses; obesity; NAFLD; preterm birth; echocardiography; fetal cardiology; Cardiology Consult Service; General Cardiology Outpatient Clinic

Visit the Divanovic Lab.

BA: DePauw University, Greencastle, IN, 1998.

MS: Oklahoma State University, Stillwater, OK, 2000.

PhD: University of Cincinnati, Cincinnati, OH, 2005.

Post Doc: Cincinnati Children’s Hospital Medical Center, 2010

Allen JL, Flick LM, Divanovic S, Jackson SW, Bram R, Rawlings D, Finkelman FD, Karp CL. Cutting Edge: Regulation of TLR4-driven B cell proliferation by RP105 is not B cell-autonomous. J Immunol. 2012;188:2065.

Korfhagen TR, Kitzmiller J, Chen G, Sridharan A, Haitchi HM, Hegde RS, Divanovic S, Karp CL, Whitsett JA. SAM-pointed domain ETS factor mediates epithelial cell-intrinsic innate immune signaling during airway mucous metaplasia. PNAS. 2012;109:16630.

Divanovic S, Sawtell NM, Trompette A, Warning JI, Dias A, Cooper AM, Yap GS, Arditi M, Shimada K, DuHadaway JB, Prendergast GC, Basaraba RJ, Mellor AL, Munn DH, Aliberti J, Karp CL. Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection. J Infect Dis. 2012;205:152-61.

Divanovic S, Trompette A, Jamie I. Ashworth, Marepalli B. Rao, Karp CL. Therapeutic enhancement of protective immunity during experimental Leishmania major infection. PLoS Neglected Tropical Dis. 2011;5:e1316.

Sheridan R, Lampe K, Shanmukhappa SK, Putnam P, Keddache M, Divanovic S, Bezerra J, Hoebe K. Lampe1: an ENU-germline mutation causing spontaneous hepatosteatosis identified through targeted exon-enrichment and next-generation sequencing. PLoS One. 2011;6:e21979.

Trompette A, Divanovic S, Visintin A, Blanchard C, Hegde RS, Madan R, Torne PS, Wills-Karp M, Gioannini TL, Weiss JP, Karp CL. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature. 2009;457:585-8.

Divanovic S, Trompette A, Petiniot LK, Allen JL, Flick LM, Belkaid Y, Madan R, Haky JJ, Karp CL. Regulation of TLR4 signaling and the host interface with pathogens and danger: the role of RP105. J Leukocyte Biol. 2007;82:265-271.

Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, Finberg RW, Tarakhovsky A, Vogel SN, Belkaid Y, Kurt-Jones EA, Karp CL. Inhibition of TLR4/MD-2 signaling by RP105/MD-1. J Endotoxin Res. 2005;11:363-8.

Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, Finberg RW, Tarakhovsky A, Vogel SN, Belkaid Y, Kurt-Jones EA, Karp CL. Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105. Nature Immunol. 2005;6:571-8.

Divanovic S, Lai ACK. Cytokine induction in human cord blood lymphocytes after pulsing with UV-inactivated influenza viruses. Immunology Lett. 2004;94:201-7.

Marie-Dominique Filippi, PhD

is interested in dissecting the molecular mechanism of hematopoietic cell migration. Because hematopoietic cells are utilized for the therapy of multiple blood diseases and neutrophils are responsible for maintaining an immunocompetence status, understanding the molecular mechanism of normal hematopoietic cell functions is of potential therapeutic importance.
Visit the Filippi Lab.

513-636-0991 Marie-Dominique.Filippi@cchmc.org

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Marie-Dominique Filippi, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-0991

Fax 513-636-3768

Email Marie-Dominique.Filippi@cchmc.org

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Biography

Dr. Filippi is particularly interested in dissecting the molecular mechanism of hematopoietic cell migration, including neutrophils and hematopoietic stem cells in physiological settings. Migration is a critical function of hematopoietic cell in which actin cytoskeleton reorganization plays a central role. Because hematopoietic cells are utilized for the therapy of multiple blood diseases and neutrophils are responsible for maintaining an immunocompetence status, understanding the molecular mechanism of normal hematopoietic cell functions is of potential therapeutic importance. The small RHO GTPase family, members of the Ras superfamily, including Rac, RHO and CDC42, play key roles in regulating many of these functions. During her post-doc in the laboratory of Dr. David Williams, they have demonstrated that two highly related proteins, Rac1 and Rac2, of the small Rho GTPase family, have distinct functions in the control of hematopoietic cell functions. In particular in neutrophils, they have shown that both Rac1 and Rac2 regulate cell migration but with distinct mechanism (Gu and Filippi et al, Science 2003) both in vitro and in vivo. In addition to this work, they have dissected the sequence/determinant specificity of Rac2 versus Rac1 functions in neutrophils and demonstrated that Rac2 controls its functions, at least in part, by distinct subcellular distributions of these GTPases (Tao et al, Blood 2002, Filippi et al, Nat Immunol 2004), highlighting one important mechanism controlling cellular functions.

Dr. Filippi's laboratory, in collaboration Dr. Yi Zheng, is now focused on determining the role of CDC42 and RhoA in neutrophil migration and in determining specifically the role of RhoA in hematopoietic stem cell migration and proliferation using gene targeted knock out mice for CDC42 and RhoA and their respective regulator CDC42GAP and 190RhoGAP. These studies will use in vitro and in vivo assays of cell migration as well as immunofluorescence microscopy to study cytoskeleton rearrangement associated with cell migration.

The long term goal of these studies is to identify new molecular targets of potential therapeutic importance.

Visit the Filippi Lab.

PharmD: University of Rene Descartes, Paris, France, 1998.

Residency: Hematopathology, University of Rene Descartes, Assistance public Hospital of Paris, Paris, France.

Certification: Hematopathology, 2001.

PhD: University of Denis Diderot, Paris, France, 2001.

Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010 Feb 4;115(5):936-47.

Szczur K, Zheng Y, Filippi MD. The small Rho GTPase Cdc42 regulates neutrophil polarity via CD11b integrin signaling. Blood. 2009 Nov 12;114(20):4527-37.

Xu H, Eleswarapu S, Geiger H, Szczur K, Daria D, Zheng Y, Settleman J, Srour EF, Williams DA, Filippi MD. Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential. Blood. 2009 Oct 22;114(17):3557-66.

Gu Y, Harley IT, Henderson LB, Aronow BJ, Vietor I, Huber LA, Harley JB, Kilpatrick JR, Langefeld CD, Williams AH, Jegga AG, Chen J, Wills-Karp M, Arshad SH, Ewart SL, Thio CL, Flick LM, Filippi MD, Grimes HL, Drumm ML, Cutting GR, Knowles MR, Karp CL. Identification of IFRD1 as a modifier gene for cystic fibrosis lung disease. Nature. 2009 Apr 23;458(7241):1039-42.

Monk KR, Wu J, Williams JP, Finney BA, Fitzgerald ME, Filippi MD, Ratner N. Mast cells can contribute to axon-glial dissociation and fibrosis in peripheral nerve. Neuron Glia Biol. 2007 Aug;3(3):233-44.

Daria D, Filippi MD, Knudsen ES, Faccio R, Li Z, Kalfa T, Geiger H. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood. 2008 Feb 15;111(4):1894-902.

Uchida K, Beck DC, Yamamoto T, Berclaz PY, Abe S, Staudt MK, Carey BC, Filippi MD, Wert SE, Denson LA, Puchalski JT, Hauck DM, Trapnell BC. GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis. N Engl J Med. 2007 Feb 8;356(6):567-79.

Filippi MD, Szczur K, Harris CE, Berclaz PY. Rho GTPase Rac1 is critical for neutrophil migration into the lung. Blood. 2007 Feb 1;109(3):1257-64.

Szczur K, Xu H, Atkinson S, Zheng Y, Filippi MD. Rho GTPase CDC42 regulates directionality and random movement via distinct MAPK pathways in neutrophils. Blood. 2006 Dec 15;108(13):4205-13.

Wang L, Yang L, Filippi MD, Williams DA, Zheng Y. Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment. Blood. 2006 Jan 1;107(1):98-105.

Fred D. Finkelman, MD

uses mouse models to study the roles of antibodies and cytokines in health and disease. Particular interests include allergic disorders, parasitic worm infections, and antibody-mediated disorders.

513-636-6656 finkelfd@ucmail.uc.edu

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Fred D. Finkelman, MD

Academic Affiliations

Professor, UC Department of Internal Medicine

UC Department of Pediatrics

Phone 513-636-6656

Email finkelfd@ucmail.uc.edu

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Clinical

Internal medicine; rheumatology

Research

Cytokine and antibody roles in disease and host protection.

Biography

Dr. Finkelman's group’s contributions to immunology and medicine have focused on the use of mouse models of normal and abnormal immune function. They have included the initial demonstrations that: 1) IL-4 is required for induction of IgE responses in vivo, IFN-γ promotes the induction of IgG2a responses in vivo, and IL-12 suppresses IgE responses in vivo; 2) IL-4, IL-13, IL-4Rα, and Stat6 are required for host protection against intestinal worms, and protect predominantly through effects on intestinal epithelial cells, including induction of RELMβ; 3) inflammatory stimuli are required to induce dendritic cells to present antigen in a stimulatory, rather than a tolerogenic fashion; 4) complement and macrophages are required for development of murine transfusion-related acute lung injury; 5) rapid desensitization with anti-FcεRIα monoclonal antibody is a safe and effective way to rapidly suppress IgE-mediated disorders; and 6) immunoglobulin isotypes that are relatively ineffective in the induction of antibody effector mechanisms protect against inflammatory disease.

In addition, his group has developed three important in vivo techniques: 1) the use of anti-IgD antibodies to stimulate polyclonal B cell and T cell activation and antibody secretion; 2) the use of cytokine/anti-cytokine monoclonal antibody complexes to induce long-lasting increases in cytokine effects; and 3) the in vivo cytokine capture assay for measurement of in vivo cytokine secretion.

BA: Queens College, Queens, NY, 1967.

MD: Yale University School of Medicine, New Haven, CN, 1971.

Residency: Internal Medicine, Yale-New Haven Hospital, New Haven, CN.

Fellowship: Laboratory of Immunology, NIAID, NIH, Bethesda, MD.

Fellowship: Rheumatology, University of Texas-Southwestern Medical School, Dallas, TX.

Certification: Internal Medicine, 1976; Rheumatology, 1980.

Strait RT, Posgai MT, Mahler A, Barasa N, Jacob CO, Köhl J, Ehlers M, Stringer K, Shanmukappa SK, Witte D, Hossain MM, Khodoun M, Herr AB, Finkelman FD. IgG1 protects against renal disease in a mouse model of cryoglobulinemia. Nature. 2014.

Khodoun M, Kucuk ZY, Strait RT, Krishnamurthy D, Janek K, Lewkowich IP, Morris SE, Finkelman FD. Rapid polyclonal desensitization with antibodies to IgE and FcεRIα. J Allergy Clin. Immunol. 2013 133(6):1555-64.

Strait RT, Hicks W, Barasa N, Mahler A, Khodoun M, Köhl J, Stringer K, Witte D, Van Rooijen N, Susskind BM, Finkelman FD. MHC class I-specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion related acute lung injury in mice. J Exp Med. 2011 208(12):2525-44.

Herbert, DR, Yang J-Q, Hogan SP, Groschwitz K, Khodoun M, Munitz A, Orekov T, Perkins C, Wang Q, Brombacher F, Urban JF Jr, Rothenberg ME, Finkelman FD. Intestinal epithelial cell secretion of RELMβ protects against gastrointestinal worm infection. J Exp Med. 2009 206(13):2947-57.

Strait RT, Morris SC, Finkelman FD. IgG blocking antibodies inhibit IgE-mediated anaphylaxis in vivo through both antigen interception and FcγRIIb crosslinking. J Clin Invest. 2006 116(3):833-41.

Morris SC, Madden KB, Adamovicz JJ, Gause WC, Hubbard BR, Gately MK, Finkelman FD. Effects of Interleukin-12 on in vivo cytokine gene expression and Ig isotype selection. J Immunol. 1994 152(3):1047-56.

Urban JF Jr, Katona IM, Paul WE, Finkelman FD. Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice. Proc Natl Acad Sci. USA. 1991 88(13):5513-7.

Finkelman FD, Lees A, Birnbaum R, Gause WC, Morris SC. Dendritic cells can present antigen in vivo in a tolerogenic or an immunogenic fashion. J Immunol. 1996 157(4):1406-14.

Urban JF Jr, Noben-Trauth N, Donaldson DD, Madden KB, Morris SC, Collins M, Finkelman FD. IL-13, IL-4Rα, and Stat6 are required for the expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity. 1998 8(2):255-64.

Finkelman FD, Katona IM, Mosmann TR, Coffman RL. Interferon-γ regulates the isotypes of immunoglobulin secreted during in vivo humoral immune responses. J Immunol. 1988 140(4):1022-7.

Grants

Suppression of established IgE-mediated disease. Principal Investigator. United States Veterans Authority. Apr 2012 - Mar 2016.

Induction of food allergy in mice by allergen inhalation. Principal Investigator. DoD. Jul 2013 - Jun 2016.

Rapid suppression of food allergy with anti-FceRIa antibody. Principal Investigator. Food Allergy Research and Education. Jun 2014 - May 2017.

Suppression of IgE-mediated disease by polyclonal rapid desensitization. Principal Investigator. National Institutes of Health/National Institute of Allergy and Infectious Diseases. Jul 2014 - Jun 2018. 1R01AI113162-01.

Matthew J. Flick, PhD

is working to understand how hemostatic factors in the blood that are responsible for clotting also drive inflammation in the context of infection and diseases such as arthritis and fatty liver disease.

513-636-6628 matthew.flick@cchmc.org

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Matthew J. Flick, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-6628

Email matthew.flick@cchmc.org

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Coagulation factors and inflammatory diseases

Biography

Research Interests and Focus:

1. Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all cancers, is rapidly becoming the second leading cause of cancer deaths in the U.S., and is estimated to cost the health care system $2.4 billion each year. Patients with PDAC have a five-year survival rate of 7%, and that number drops to 2% for individuals with metastatic disease. Unfortunately, there has been little progress in shifting patient outcome over the past 40 years, highlighting the need for innovative approaches to define the molecular pathways that influence PDAC development. PDAC is typically initiated by acinar cells acquiring an activating mutation in the KRAS protooncogene, which causes cells to transition to a duct-like state known as acinar-ductal metaplasia (ADM). ADM progresses to pancreatic intraepithelial neoplasia (PanIN) lesions that develop into PDAC. A key transcriptional response to ADM/PanIN development is the dramatically increased expression of the physiological activator of the coagulation system, Tissue Factor (TF). Our research builds on a known relationship between pancreatic cancer and high-level activity of the blood coagulation system, but is unique in that it will define newly discovered mechanisms of crosstalk by which specific coagulation factors in the TME promote PDAC pathogenesis.

2. The pervasive gram-positive bacteria Staphylococcus aureus is a common pathogen that is the causative agent for a wide spectrum of diseases including skin infections, pneumonia, bacteremia, toxic-shock syndrome and sepsis. Notably, this pathogen has evolved and maintained a number of proteins that directly engage the host hemostatic system, including factors that directly interact with the host coagulation factor fibrinogen. The long-term goal of this research program is to understand how bacterial derived proteins interact with host factors to promote bacterial virulence in the context of blood-born infections. This work will provide novel insight into the molecular pathways by which S. aureus invades and disseminates within host tissues and may shed light into novel strategies for eliminating this potentially devastating infectious agent.

3. Obesity is a worldwide epidemic linked to numerous disease sequelae, including non-alcoholic fatty liver disease (NAFLD). This spectrum disorder can progress from the simple accumulation of triglycerides within hepatocytes (i.e., steatosis), to inflammatory steatohepatitis, to organ failure secondary to irreversible liver fibrosis and cirrhosis. Dysregulation of the coagulation system has been documented in both patients with fatty liver disease and animal models of obesity, but any contribution to disease progression has remained largely undefined. Using a murine model of high fat diet (HFD)-induced obesity, this research program is testing the hypothesis that thrombin activity and fibrin deposition drive local inflammatory events promoting the progression of obesity and obesity-associated disease sequelae. Comparative studies of wild-type mice with genetically imposed deficiencies or functional alterations in prothrombin, fibrinogen and other associated coagulation factor components suggests that the thrombin-fibrinogen axis influences obesity pathogenesis by controlling local inflammatory processes that drive metabolic inflammation leading to fibrin(ogen)-mediated HFD-induced weight gain/obesity. This research has far-reaching implications for the treatment and prevention of all the downstream sequelae of obesity and even the development of diet-mediated weight gain itself.

BS: Xavier University, Cincinnati, OH.

PhD: Purdue University, West Lafayette, IN.

Post-doctoral Fellow: Cincinnati Children’s Hospital and Medical Center, Division of Developmental Biology, Cincinnati, OH.

Shaw MA, Kombrinck KW, McElhinney KE, Sweet DR, Flick MJ, Palumbo JS, Cheng M, Esmon NL, Esmon CT, Brill A, Wagner DD, Degen JL, Mullins ES. Limiting prothrombin activation to meizothrombin is compatible with survival but significantly alters hemostasis in mice. Blood. 2016 Aug 4;128(5):721-31.

Ko YP, Flick MJ. Fibrinogen Is at the Interface of Host Defense and Pathogen Virulence in Staphylococcus aureus Infection. Semin Thromb Hemost. 2016 Jun;42(4):408-21.

Joshi N, Kopec AK, Ray JL, Cline-Fedewa H, Nawabi A, Schmitt T, Nault R, Zacharewski TR, Rockwell CE, Flick MJ, Luyendyk JP. Fibrin deposition following bile duct injury limits fibrosis through an αMβ2-dependent mechanism. Blood. 2016 Jun 2;127(22):2751-62.

Motley MP, Madsen DH, Jürgensen HJ, Spencer DE, Szabo R, Holmbeck K, Flick MJ, Lawrence DA, Castellino FJ, Weigert R, Bugge TH. A CCR2 macrophage endocytic pathway mediates extravascular fibrin clearance in vivo. Blood. 2016 Mar 3;127(9):1085-96.

Yuasa M, Mignemi NA, Nyman JS, Duvall CL, Schwartz HS, Okawa A, Yoshii T, Bhattacharjee G, Zhao C, Bible JE, Obremskey WT, Flick MJ, Degen JL, Barnett JV, Cates JM, Schoenecker JG. Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification. J Clin Invest. 2015 Sep;125(9):3723.

Adams GN, Rosenfeldt L, Frederick M, Miller W, Waltz D, Kombrinck K, McElhinney KE, Flick MJ, Monia BP, Revenko AS, Palumbo JS. Colon Cancer Growth and Dissemination Relies upon Thrombin, Stromal PAR-1, and Fibrinogen. Cancer Res. 2015 Oct 1;75(19):4235-43.

Prasad JM, Gorkun OV, Raghu H, Thornton S, Mullins ES, Palumbo JS, Ko YP, Höök M, David T, Coughlin SR, Degen JL, Flick MJ. Mice expressing a mutant form of fibrinogen that cannot support fibrin formation exhibit compromised antimicrobial host defense. Blood. 2015 Oct 22;126(17):2047-58.

Yuasa M, Mignemi NA, Nyman JS, Duvall CL, Schwartz HS, Okawa A, Yoshii T, Bhattacharjee G, Zhao C, Bible JE, Obremskey WT, Flick MJ, Degen JL, Barnett JV, Cates JM, Schoenecker JG. Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification. J Clin Invest. 2015 Aug 3;125(8):3117-31.

Joshi N, Kopec AK, O'Brien KM, Towery KL, Cline-Fedewa H, Williams KJ, Copple BL, Flick MJ, Luyendyk JP. Coagulation-driven platelet activation reduces cholestatic liver injury and fibrosis in mice. J Thromb Haemost. 2015 Jan;13(1):57-71.

Raghu H, Cruz C, Rewerts CL, Frederick MD, Thornton S, Mullins ES, Schoenecker JG, Degen JL, Flick MJ. Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation and bone erosion. Blood. 2015 Jan 15;125(3):427-37.

Grants

NIH, National Institute of Arthritis and Musculoskeletal and Skin Diseases Research. Director. Cincinnati Rheumatic Diseases Core Center. Aug 2011-Jun 2016. 2P30 AR47363.

Hemostatic factors and sickle cell disease. Co-investigator. NIH. Dec 2011-Nov 2016. R01 HLI12603.

H. Leighton (Lee) Grimes, PhD Director, Cancer Pathology Program, Division of Experimental Hematology & Division of Pathology

focuses on the transcriptional control of normal and malignant hematopoiesis. The goal of his research is to understand how normal blood cells are formed, and to use this information to dissect the molecular pathogenesis of marrow failure and leukemia.
Visit the Grimes Lab.

513-636-6089 lee.grimes@cchmc.org

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H. Leighton (Lee) Grimes, PhD

Director, Cancer Pathology Program, Division of Experimental Hematology & Division of Pathology

Co-Leader, Program in Hematologic Malignancies of Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-6089

Fax 513-636-5355

Email lee.grimes@cchmc.org

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Acute myelogenous leukemia; T-cell acute lymphoblastic leuekemia; severe congenital neutropenia; hematopoiesis; myelopoiesis; lineage decision; transcription factor

Visit the Grimes Lab.

Biography

Dr. Grimes has a broad background in hematopoiesis, molecular biology, and molecular oncology including modeling of hematopoiesis, myelopoiesis and leukemia. His work on the Growth factor independent-1 (Gfi1) transcriptional repressor protein has spanned the initial identification of Gfi1 in a model of leukemia and the role of Gfi1 in normal myeloid biology, to the identification of GFI1 mutations in patients with severe congenital neutropenia (SCN) and non-immune chronic idiopathic neutropenia of adults (NI-CINA). His work utilizes Gfi1 as a molecular probe to understand both normal myeloid development and innate immune action, as well as marrow failure and transformation.

PhD: Immunology and Molecular Pathology, University of Florida, Gainesville, FL.

Postdoctoral Fellow: Fox Chase Cancer Center.

Olsson A, Venkatasubramanian M, Chaudhri VK, Aronow BJ, Salomonis N, Singh H, Grimes HL. Single-cell analysis of mixed-lineage states leading to a binary cell fate choice. Nature. 2016 Aug 31.

Meyer SE, Qin T, Muench DE, Masuda K, Venkatasubramanian M, Orr E, Suarez L, Gore SD, Delwel R, Paietta E, Tallman MS, Fernandez H, Melnick A, Le Beau MM, Kogan S, Salomonis N, Figueroa ME, Grimes HL. DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia. Cancer Discovery. 2016; May;6(5):501-15.

Muench DE, Grimes HL. Transcriptional Control of Stem and Progenitor Potential. Curr Stem Cell Rep. 2015 Sep;1(3):139-150.

Nayak RC, Trump LR, Aronow BJ, Myers K, Mehta P, Kalfa T, Wellendorf AM, Valencia CA, Paddison PJ, Horwitz MS, Grimes HL#, Lutzko C#, Cancelas JA#. Pathogenesis of ELANE-mutant severe neutropenia revealed by induced pluripotent stem cells. J Clin Invest. 2015 Aug 3;125(8):3103-16. # shared corresponding author.

Cumaraswamy AA, Lewis AM, Geletu M, Todic A, Diaz DB, Cheng XR, Brown CE, Laister RC, Muench D, Kerman K, Grimes HL, Minden MD, Gunning PT. Nanomolar-Potency Small Molecule Inhibitor of STAT5 Protein. ACS Med Chem Lett. 2014 Sep 19;5(11):1202-1206.

Velu CS, Chaubey A, Phelan JD, Horman SR, Wunderlich M, Guzman ML, Jegga AG, Zeleznik-Le NJ, Chen J, Mulloy JC, Cancelas JA, Jordan CT, Aronow BJ, Marcucci G, Bhat B, Gebelein B, Grimes HL. Therapeutic antagonists of microRNAs deplete leukemia-initiating cell activity. J Clin Invest. 2014 Jan;124(1):222-36.

Phelan JD, Saba AI, Olsson A, Zeng H, Kosan C, Messer MS, Hildeman D, Aronow B, Möröy T, Grimes HL. Growth factor independent-1 maintains Notch1-dependent transcriptional programming of lymphoid precursors. PLoS Genetics. 2013;9(9):e1003713.

Khandanpour C*, Phelan JD*, Vassen L, Schutte J, Chen R, Horman SR, Gaudreau MC, Krongold J, Zhu J, Paul WE, Duhrsen U, Gottgens B, Grimes HL# Moroy T#. Growth factor independence 1 (Gfi1) antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia. Cancer Cell. 2013 Feb 11;23(2):200-14. * equal first author, # shared corresponding author.

Grants

Developing Novel STAT5 Protein Inhibitors for treatment of leukemias. Principal Investigator. National Cancer Institute. Sept 2014–Sept 2017. R21CA186945.

MicroRNA in Acute Myeloid Leukemia. Principal Investigator. National Cancer Institute. Jul 2011–Apr 2017. R01CA159845.

Mechanisms of granulocyte homeostasis. Principal Investigator. National Heart Lung and Blood Institute. Sept 2015–Sept 2019. R01HL122661.

A rapid spontaneous murine model of CN-AML. Principal Investigator. National Cancer Institute. Jul 2016-Jun 2019. R01CA196658.

John B. Harley, MD, PhD Director, Center for Autoimmune Genomics and Etiology (CAGE)

is a rheumatologist and biochemist with special clinical and research interests in the genetic etiology of inflammatory diseases. His experimental focus is the many genetic effects and environmental causes of systemic lupus erythematosus (SLE) and related inflammatory diseases. Through this work, nearly 50 genes are known and Epstein Barr virus has been identified to trigger the systemic autoimmunity of lupus. Dr. Harley also builds infrastructure with which to do high throughput genotyping, expression analysis, and epigenetics, which he makes available to his colleagues from around the world. In recent experiments, Dr. Harley organized the logistics of managing >18,000 subjects at >30,000 genetic markers, 3200 subjects at 1.2 million markers, and 10,000 subjects at 196,000 markers. Dr. Harley is committed to all of the steps between association detection through replication and toward identifying the possible functional genetic variants and to pursuing their biology.

513-803-3665 john.harley@cchmc.org

High Res

John B. Harley, MD, PhD

Director, Center for Autoimmune Genomics and Etiology (CAGE)

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-3665

Email john.harley@cchmc.org

Cobb BL, Fei Y, Jonsson R, Bolstad AI, Brun JG, Rischmueller M, Lester SE, Witte T, Illei G, Brennan M, Bowman S, Moser KL, Harley JB, Sawalha AH. Genetic association between methyl-CpG binding protein 2 (MECP2) and primary Sjögren’s syndrome. Ann Rheum Dis. 2010; 69(9): 1731-2.

Kim-Howard X, Maiti AK, Anaya J-M, Bruner GR, Brown E, Merrill JT, Edberg JC, Petri MA, Reveille JD, Ramsey-Goldman R, Alarcon GS, Vyse TJ, Gilkeson G, Kimberly RP, James JA, Guthridge JM, Harley JB, Nath SK. ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash, and immunologic manifestations in lupus patients with European ancestry. Ann Rheum Dis. 2010.

Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Res. 2010; 20(2):170-179.

Harley JB, James JA. Everyone comes from somewhere: systemic lupus erythematosus and Epstein-Barr virus, induction of host interferon (INF) and humoral anti-EBNA1 immunity. Arthritis Rheum. 2010.

Bronson PG, Komorowski LK, Ramsay PP, May SL, Noble J, Lane JA, Thomson G, Claas FH, Seldin MF, Kelly JA, Harley JB, Moser KL, Gaffney PM, Behrens T, Criswell LA, Barcellos LF. Analysis of maternal-offspring HLA compatibility, parent-of-origin and noninherited effects for HLA-DRB1 in systemic lupus erythematosus. Arthritis Rheum. 2010.

Heinlen LD, McClain MT, Ritterhouse LL, Bruner BF, Edgerton CC, Keith MP, James JA, Harley JB. 60kD Ro and nRNP A frequently initiate human lupus autoimmunity. PLoS ONE. 2010 5(3):e9599.

Sammalisto S, Hiekkalinna T, Schwander K, Kardia S, Weder AB, Rodriquez BL, Doria A, Kelly JA, Bruner GR, Harley JB, Redline S, Larkin EK, Patel SR, Ewan AJ, Weber JL, Perola M, Peltonen L. Genome-wide linkage screen for stature and body mass index in 3.032 families: evidence for sex-and population-specific genetic effects. Eur J Hum Genet. 2009 Jan 1;17(2):258-266.

Poole BD, Templeton AK, Guthridge JM, Brown EJ, Harley JB, James JA. Aberrant Epstein-Barr viral infection in systemic lupus erythematosus. Autoimmun Rev. 2009 Feb;8(4):337-42.

Poole BD, Schneider RI, Guthridge JM, Velte CA, Reichlin M, Harley JB, James JA. Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus. Arthritis Rheum. 2009 Feb 26; 60(3):848-859.

Han S, Kim-Howard X, Deshmukh H, Kamatani Y, Viswanathan P, Guthridge JM, Thomas K, Kaufman KM, Ojwang J, Rojas-Villarraga A, Baca V, Orozco L, Rhodes B, Choi CB, Gregersen PK, Merrill JT, James JA, Gaffney PM, Moser KL, Jacob CO, Kimberly RP, Harley JB, Bae SC, Anaya JM, Alarcon-Riquelme ME, Matsuda K, Vyse TJ, Nath SK. Evaluation of imputation-based association in and around the Integrin-α-M (ITGAM) gene and replication of robust association between a non-synonymous functional variant within ITGAM and systemic lupus erythematosus (SLE). Hum Mol Genet. 2009 Mar 15;18(6):1171-80.

Andrew B. Herr, PhD

studies protein-protein interactions involved in immune receptor signaling and bacterial pathogenesis. His lab uses X-ray crystallography to solve the atomic structures of proteins along with techniques of biophysical chemistry to understand their interactions in solution. The goal is to understand the molecular basis for autoimmune responses and recurrent bacterial infections, and to develop new therapeutic applications.
Visit the Herr Lab.

513-803-7490 andrew.herr@cchmc.org

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Andrew B. Herr, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-7490

Email andrew.herr@cchmc.org

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Structural biology and biophysics of antibodies; immune receptors; bacterial surface proteins

Visit the Herr Lab.

Biography

Andrew Herr, PhD, is an associate professor in the Division of Immunobiology and Center for Systems Immunology, with an affiliate appointment in the Division of Infectious Diseases at Cincinnati Children's within the UC Department of Pediatrics. Dr. Herr completed his thesis work in molecular biophysics from Washington University in St. Louis, and completed his postdoctoral work in structural immunology at the California Institute of Technology as a Damon Runyon Research Fellow. He was recruited to the University of Cincinnati College of Medicine as an Ohio Eminent Scholar in Structural Biology before moving to Cincinnati Children’s Hospital.

Dr. Herr solved the first structure of a human IgA1 antibody bound to its cognate Fc receptor while at Caltech, and his lab has continued to study antibodies and immune receptors implicated in autoimmune diseases. In addition, the lab is studying a family of related collagen-specific immune receptors such as glycoprotein VI, which activates platelets upon exposure to fibrous collagen. The Herr lab also studies mechanisms of bacterial pathogenesis. Specifically, they discovered the zinc-dependent mechanism of intercellular adhesion in bacterial biofilms formed by Staphylococcus epidermidis and S. aureus. Biofilms are specialized bacterial colonies that are highly resistant to antibiotics and immune responses, so developing novel therapies to prevent biofilm formation is of high importance.

Before joining the faculty at Cincinnati Children's within the University of Cincinnati College of Medicine, Dr. Herr was an Ohio Eminent Scholar in Structural Biology at the University of Cincinnati College of Medicine and served as an associate director of the Cincinnati Medical Scientist (MD/PhD) Training Program. Dr. Herr received the 2014 Emerging Entrepreneurial Achievement Faculty Award from UC for his work to commercialize a novel anti-infective therapy based on his lab’s research.

BA: Oral Roberts University, Tulsa, OK, 1993.

PhD: Washington University Medical School, St. Louis, MO, 1999.

Postdoc: California Institute of Technology, Pasadena, CA, 2003.

Visit the Khurana Hershey Lab.

Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, Zuo X, Kao CC, Herr AB, Li P. Cyclic GMP-AMP synthase is activated by double-stranded DNA-induced oligomerization. Immunity. 2013 Dec 12;39(6):1019-31.

Conrady DG, Wilson JJ, Herr AB. Structural basis for Zn2+-dependent intercellular adhesion in staphylococcal biofilms. Proc Natl Acad Sci U S A. 2013 Jan 15;110(3):E202-11.

Herr AB, Conrady DG. Thermodynamic analysis of metal ion-induced assembly . Methods Enzymol . 2011;488:101-21.

Herr AB, Farndale RW. Structural insights into the interactions between platelet receptors and fibrillar collagen. J Biol Chem. 2009 Jul 24;284(30):19781-5.

Horii K, Brooks MT, Herr AB. Convulxin forms a dimer in solution and can bind eight copies of glycoprotein VI: Implications for platelet activation. Biochemistry. 2009 Apr 7;48(13):2907-14.

Conrady DG, Brescia CC, Horii K, Weiss AA, Hassett DJ, Herr AB. A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19456-61.

Gomes, MM, SB Wall, K Takahashi, J Novak, MB Renfrow, and AB Herr. Analysis of IgA1 N-glycosylation and its contribution to FcaRI binding. Biochemistry. 2008 Oct 28;47(43):11285-99.

Horii K, Kahn ML, Herr AB. Structural basis for platelet collagen responses by the immune-type receptor glycoprotein VI. Blood. 2006 Aug 1;108(3):936-42.

Herr, AB, ER Ballister, and PJ Bjorkman. Insights into IgA-mediated immune responses from the crystal structures of human FcaRI and its complex with IgA1-Fc. Nature. 2003 Jun 5;423(6940):614-20.

Ornitz DM, Herr AB, Nilsson M, Westman J, Svahn CM, Waksman G. FGF binding and FGF receptor activation by synthetic heparan-derived di- and trisaccharides. Science. 1995 Apr 21;268(5209):432-6.

Gurjit (Neeru) Khurana Hershey, MD, PhD Director, Division of Asthma Research

is the principal investigator of a federally funded Asthma and Allergic Diseases Cooperative Research Center which supports, in part, the asthma and allergy-based Greater Cincinnati Pediatric Clinic Repository. She also focuses on elucidating the genetic and environmental factors that contribute to the development of asthma and eczema.

513-636-7054 gurjit.hershey@cchmc.org

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Gurjit (Neeru) Khurana Hershey, MD, PhD

Director, Division of Asthma Research

Co-Director, Office of Pediatric Clinical Fellowships

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7054

Fax 513-636-1657

Email gurjit.hershey@cchmc.org

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Visit the Khurana Hershey Lab.

Clinical

Asthma; allergic rhinitis; food allergy; urticaria

Research

Genetics of allergy and asthma; cytokines; signaling pathways

Biography

Gurjit Khurana Hershey, MD, PhD, received a BS degree from the University of Iowa, and MD and PhD degrees from Washington University School of Medicine. After completing pediatric residency and an allergy/immunology fellowship at St. Louis Children’s Hospital, Dr. Khurana Hershey joined the faculty at Cincinnati Children’s Hospital Medical Center within the University of Cincinnati College of Medicine. She now directs the Division of Asthma Research at Cincinnati Children’s Hospital Medical Center and is the director of the Medical Scientist Training Program at the University of Cincinnati College of Medicine.

In addition to her clinical duties, Dr. Khurana Hershey directs an NIH-funded research program focused on the genetics and genomics of allergic inflammation with a focus on cytokines and signal transduction. Her research has been continuously funded for over fifteen years. She is the principal investigator of an NIH-funded Asthma and Allergic Diseases Cooperative Research Center (AADCRC), and is also the PI of the Inner City Asthma Consortium, an NIH funded subcontract. She is the PI of the UC T32 MSTP training grant. In addition to her research contributions, she is an outstanding clinician and teacher/mentor. Several of her trainees now hold academic faculty positions. She is the recipient of the 2013 Cincinnati Children’s Educational Achievement Award.

Dr. Khurana Hershey is a fellow of the American Pediatric Society and the American Academy of Allergy, Asthma and Immunology. She serves on the Executive Council of the American Academy of Asthma, Allergy and Immunology Program Committee, is the chair of the Grant Review Committee and appointed vice chair of the Basic and Immunology Interest Section. She is a member of the Editorial Board of the Journal of Allergy and Clinical Immunology. She was recently named One of the Five Leading Women in Healthcare in the Greater Cincinnati Metropolitan Area, and Outstanding Woman at Cincinnati Children’s Hospital Medical Center.

BS: University of Iowa, Iowa City, IA, 1985.

PhD: Washington University School of Medicine, St. Louis, MO, 1990.

MD: Washington University School of Medicine, St. Louis, MO, 1992.

Residency: St. Louis Children's Hospital, St. Louis, MO, 1992-1995.

Fellowship: St. Louis Children's Hospital, St. Louis, MO, 1995-1997.

Board Certification: American Board of Pediatrics, 2009 - Present.

Board Certification: American Board of Allergy and Immunology, 2008 - Present.

Biagini Myers JM, Martin LJ, Butsch Kovacic M, Mersha TB, He H, Pilipenko V, Lindsey MA, Ericksen MB, Bernstein DI, LeMasters GK, Lockey JE, Khurana Hershey GK. Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma. J Allergy Clin Immunol. 2014 May 13. pii: S0091-6749(14)00520-X.

Wood RA, Togias A, Wildfire J, Visness CM, Matsui EC, Gruchalla R, Hershey G, Liu AH, O’Connor GT, Pongracic JA, Zoratti E, Little F, Granada M, Kennedy S, Durham SR, Shamji MH, Busse WW. Development of cockroach immunotherapy by the Inner-City Asthma Consortium. J Allergy Clin Immunol. 2014 Mar;133(3)846-52.

Zhang Z, Xiao C, Gibson AM, Bass SA, Khurana Hershey GK. EGFR signaling blunts allergen-induced IL-6 production and Th17 responses in the skin and attenuates development and relapse of atopic dermatitis. J Immunol. 2014 Feb 1:192(3):859-66.

Kinker KG, Gibson AM, Bass SA, Day BP, Deng, J, Medvedovic M, Figueroa JA, Hershey GK, Chen W. Overexpression of dimethylarginine dimethylaminohydrolase 1 attenuates airway inflammation in a mouse model of asthma. PloS One. 2014 Jan 10;9 (1):e85148.

Acciani TH, Brandt EB, Khurana Hershey GK, Le Cras TD. Diesel exhaust particle exposure increases severity of allergic asthma in young mice and children. Clin Exp Allergy. 2013 Dec;43(12):1406-18.

Brandt EB, Kovacic MB, Lee GB, Gibson AM, Acciani TH, Le Cras TD, Budelsky AL, Khurana Hershey GK. Diesel exhaust particle induction of IL17A contributes to severe asthma. J Allergy Clin Immunol. 2013 Nov:132(5);1194-1204.

Brandt EB, Gibson AM, Bass S, Khurana Hershey GK. Exacerbation of Allergen-Induced Eczema in TLR4- and TRIF-Deficient Mice. J Immunol. 2013 Oct 1;191(7):3519-25.

Chen W, Sivaprasad U, Gibson AM, Ericksen MB, Cunningham CM, Bass SA, Kinker KG, Finkelman FD, Wills-Karp M, Khurana Hershey GK. IL-13 receptor α2 contributes to development of experimental allergic asthma. J Allergy Clin Immunol. 2013 Oct;132(4):951-958.

Lee GB, Brandt EB, Xiao C, Gibson AM, Le Cras TD, Brown LA, Fitzpatrick AM, Khurana Hershey GK. Diesel exhaust particles induce cysteine oxidation and S-glutathionylation in house dust mite induced murine asthma. PLoS One. 2013;8(3):e60632.

Mintz-Cole RA, Brandt EB, Bass SA, Gibson AM, Reponen T, Khurana Hershey GK. Surface availability of beta-glucans is critical determinant of host immune response to C. cladosporioides . J Allergy Clin Immunol . 2013 Jul;132(1):159-69.

David A. Hildeman, PhD Director, Immunology Graduate Program

explores the molecular factors that control the decision between tolerance and immunity within T lymphocytes. Using genetic mouse models, viruses, and MHC tetrameric reagents, the lab is focused on the molecular regulation of antigen-specific T cell responses. Dr. Hildeman is also the current director of the Immunology Graduate Program.
Visit the Hildeman Lab.

513-636-3923 david.hildeman@cchmc.org

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David A. Hildeman, PhD

Director, Immunology Graduate Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3923

Fax 513-636-5355

Email david.hildeman@cchmc.org

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Clinical

T cells; autoimmunity; sex differences in immune responses; apoptosis

Research

Molecular factors that control the decision between tolerance and immunity within T lymphocytes; staphylococcal enterotoxins, recombinant vaccinia viruses, lymphocytic choriomeningitis virus and MHC tetrameric reagents; antigen -specific T cell responses; tolerance centers on regulation of mechanisms that control the survival and death of activated T cells in vivo, namely Bcl-2 and its antagonist Bim; manipulation and regulation of antigen-specific T cell responses via novel vaccine strategies to either induce tolerance or enhance immunity; mechanisms underlying sex-based differences in T cell responses and how these differences relate to autoimmune disease.
Visit the Hildeman Lab.

PhD: University of Wisconsin-Madison, Madison, Wisconsin, 1997.

Chae HD, Siefring JE, Hildeman DA, Gu Y, Williams DA. RhoH regulates subcellular localization of ZAP-70 and Lck in T cell receptor signaling. PLoS One. 2010 Nov 12;5(11):e13970.

Chougnet CA, Tripathi P, Lages CS, Raynor J, Sholl A, Fink P, Plas DR, Hildeman DA. A major role for Bim in regulatory T cell homeostasis. J Immunol. 2011 Jan 1;186(1):156-63.

Guo F, Hildeman D, Tripathi P, Velu CS, Grimes HL, Zheng Y. Coordination of IL-7 receptor and T-cell receptor signaling by cell-division cycle 42 in T-cell homeostasis. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18505-10.

Kasten KR, Prakash PS, Unsinger J, Goetzman HS, England LG, Cave CM, Seitz AP, Mazuski CN, Zhou TT, Morre M, Hotchkiss RS, Hildeman DA, Caldwell CC. Interleukin-7 (IL-7) treatment accelerates neutrophil recruitment through gamma delta T-cell IL-17 production in a murine model of sepsis. Infect Immun. 2010 Nov;78(11):4714-22.

Tripathi P, Kurtulus S, Wojciechowski S, Sholl A, Hoebe K, Morris SC, Finkelman FD, Grimes HL, Hildeman DA. STAT5 is critical to maintain effector CD8+ T cell responses. J Immunol. 2010 Aug 15;185(4):2116-24.

Kurtulus S, Tripathi P, Opferman JT, Hildeman DA. Contracting the 'mus cells' -- does down-sizing suit us for diving into the memory pool? Immunol Rev. 2010 Jul;236:54-67. Review.

Lin AA, Wojciechowski SE, Hildeman DA. Androgens suppress antigen-specific T cell responses and IFN-γ production during intracranial LCMV infection. J Neuroimmunol. 2010 Sep 14;226(1-2):8-19.

Kasten KR, Tschöp J, Goetzman HS, England LG, Dattilo JR, Cave CM, Seitz AP, Hildeman DA, Caldwell CC. T-cell activation differentially mediates the host response to sepsis. Shock. 2010 Oct;34(4):377-83.

Kasten KR, Tschöp J, Adediran SG, Hildeman DA, Caldwell CC. T cells are potent early mediators of the host response to sepsis. Shock. 2010 Oct;34(4):327-36. Review.

Madan R, Demircik F, Surianarayanan S, Allen JL, Divanovic S, Trompette A, Yogev N, Gu Y, Khodoun M, Hildeman D, Boespflug N, Fogolin MB, Gröbe L, Greweling M, Finkelman FD, Cardin R, Mohrs M, Müller W, Waisman A, Roers A, Karp CL. Nonredundant roles for B cell-derived IL-10 in immune counter-regulation. J Immunol. 2009 Aug 15;183(4):2312-20.

Kasper Hoebe, PhD

focuses on mechanistic analysis of pathways of innate immune activation and the mechanisms underlying NK cell and CD8+ T cell development and cytolytic effector function, using forward genetic approaches. His discovery of an “endogenous adjuvant” pathway mediated by NK cell killing has led to research aimed at exploiting the knowledge obtained on NK cell-driven adaptive immune responses for the generation of new, safer vaccine approaches.
Visit the Hoebe Lab.

513-803-1056 kasper.hoebe@cchmc.org

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Kasper Hoebe, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1056

Fax 513-636-5355

Email kasper.hoebe@cchmc.org

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Innate-adaptive connection; mechanisms underlying NK cell and CD8+ T cell development; cytolytic effector function; safer vaccine approaches.
Visit the Hoebe Lab.

BS: Biology; Utrecht University, The Netherlands, 1994.

PhD: Immunology/ Pharmacology; Utrecht University, The Netherlands, 2001.

Tripathi P, Kurtulus S, Wojciechowski S, Sholl A, Hoebe K, Morris SC, Finkelman FD, Grimes HL, Hildeman DA. STAT5 is critical to maintain effector CD8+ T cell responses. J Immunol. 2010 Aug 15;185(4):2116-24.

Barnes MJ, Aksoylar H, Krebs P, Bourdeau T, Arnold CN, Xia Y, Khovananth K, Engel I, Sovath S, Lampe K, Laws E, Saunders A, Butcher GW, Kronenberg M, Steinbrecher K, Hildeman D, Grimes HL, Beutler B, Hoebe K. Loss of T cell and B cell quiescence precedes the onset of microbial flora-dependent wasting disease and intestinal inflammation in Gimap5-deficient mice. J Immunol. 2010 Apr 1;184(7):3743-54.

Krebs P, Barnes MJ, Lampe K, Whitley K, Bahjat KS, Beutler B, Janssen E, Hoebe K. NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses. Blood. 2009 Jun 25;113(26):6593-602.

Hoebe K, Beutler B. Forward genetic analysis of TLR-signaling pathways: An evaluation. Adv Drug Deliv Rev. 2008 Apr 29;60(7):824-9.

Rutschmann S, Hoebe K. Dissecting innate immunity by germline mutagenesis. Immunology. 2008;123(4):459-68.

Baccala R, Hoebe K, Kono DH, Beutler B, Theofilopoulos AN. TLR-dependent and TLR-independent pathways of type I interferon induction in systemic autoimmunity. Nature Med. 2007;13(5);543–51.

Brinkmann MM, Spooner E, Hoebe K, Beutler B, Ploegh HL, Kim YM. The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. J Cell Biol. 2007;177(2):265-75.

Crozat K, Hoebe K, Ugolini S, Hong NA, Janssen E, Rutschmann S, Mudd S, Sovath S, Vivier E, Beutler B. Jinx, an MCMV susceptibility phenotype caused by disruption of Unc13d: a mouse model of type 3 familial hemophagocytic lymphohistiocytosis. J Exp Med. 2007;204(4):853-63.

Gavin AL, Hoebe K, Duong B, Ota T, Martin C, Beutler B, Nemazee D. Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling. Science. 2006;314(5807):1936-8.

Casrouge A, Zhang SY, Eidenschenk C, Jouanguy E, Puel A, Yang K, Alcais A, Picard C, Mahfoufi N, Nicolas N, Lorenzo L, Plancoulaine S, Senechal B, Geissmann F, Tabeta K, Hoebe K, Du X, Miller RL, Heron B, Mignot C, de Villemeur TB, Lebon P, Dulac O, Rozenberg F, Beutler B, Tardieu M, Abel L, Casanova JL. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science. 2006;314(5797): 308-12.

Simon P. Hogan, PhD Director of Research, Division of Allergy and Immunology

is studying allergies, food allergies, eosinophil biology, and gastrointestinal inflammation.
Visit the Hogan Lab.

513-636-6620 simon.hogan@cchmc.org

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Simon P. Hogan, PhD

Director of Research, Division of Allergy and Immunology

Director of Admissions, Immunology Graduate Program

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-6620

Fax 513-636-3310

Email simon.hogan@cchmc.org

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Food allergies and anaphylaxis; inflammatory bowel diseases (IBD); innate immunity; gastrointestinal immunity and function; cystic fibrosis (CF)

Visit the Hogan Lab.

BSC: Australian National University, Canberra, Australia, 1998.

PhD: John Curtin School of Medical Research, Australian National University, Canberra, Australia, 1998.

Lampinen M, Waddell A, Ahrens R, Carlson M, Hogan SP. CD14+CD33+ myeloid cell-CCL11-eosinophil signature in ulcerative colitis. J Leukoc Biol. 2013 Nov;94(5):1061-70.

Waddell A, Ahrens R, Tsai YT, Sherrill JD, Denson LA, Steinbrecher KA, Hogan SP. Intestinal CCL11 and eosinophilic inflammation is regulated by myeloid cell-specific RelA/p65 in mice. J Immunol. 2013 May 1;190(9):4773-85.

Groschwitz KR, Wu D, Osterfeld H, Ahrens R, Hogan SP. Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism. Am J Physiol Gastrointest Liver Physiol. 2013 Mar 1;304(5):G479-89.

Ahrens R, Osterfeld H, Wu D, Chen CY, Arumugam M, Groschwitz K, Strait R, Wang YH, Finkelman FD, Hogan SP. Intestinal mast cell levels control severity of oral antigen-induced anaphylaxis in mice. Am J Pathol. 2012 Apr;180(4):1535-46.

Waddell A, Ahrens R, Steinbrecher K, Donovan B, Rothenberg ME, Munitz A, Hogan SP. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011 May 15;186(10):5993-6003.

Wu D, Ahrens R, Osterfeld H, Noah TK, Groschwitz K, Foster PS, Steinbrecher KA, Rothenberg ME, Shroyer NF, Matthaei KI, Finkelman FD, Hogan SP. Interleukin-13 (IL-13)/IL-13 receptor alpha1 (IL-13Ralpha1) signaling regulates intestinal epithelial cystic fibrosis transmembrane conductance regulator channel-dependent Cl- secretion. J Biol Chem. 2011 Apr 15;286(15):13357-69.

Arumugam M, Ahrens R, Osterfeld H, Kottyan LC, Shang X, Maclennan JA, Zimmermann N, Zheng Y, Finkelman FD, Hogan SP. Increased susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis. BMC Immunol. 2011 Feb 3;12:14.

Munitz A, Cole ET, Waddell A, Groschwitz K, Ahrens R, Steinbrecher K, Willson T, Han X, Denson L, Rothenberg ME,Hogan SP. Paired immunoglobulin-like receptor B (PIR-B) negatively regulates macrophage activation in experimental colitis. Gastroenterology. 2010 Aug;139(2):530-41.

Osterfeld H, Ahrens R, Strait R, Finkelman FD, Renauld JC, Hogan SP. Differential roles for the IL-9/IL-9 receptor alpha-chain pathway in systemic and oral antigen-induced anaphylaxis. J Allergy Clin Immunol. 2010 Feb;125(2):469-476.e2.

Groschwitz K, Ahrens R, Osterfeld H, Gurish MF, Abrink M, Finkelman F, Pejler G, Hogan SP. Mast cells regulate homeostatic intestinal epithelial migration and barrier function by a chymase/Mcpt4-dependent mechanism. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22381-6

Grants

Vascular Endothelium-C-Abl Kinase Underpins the Onset of a Severe Food-induced Anaphylactic Reaction. Principal Investigator. Food Allergy and Research Education. Jul 2015 - Jun 2020.

Leukocyte Immunoglobulin-like Receptor B3 in Innate Colonic Inflammation in Pediatric Ulcerative Colitis. Principal Investigator. Crohn’s and Colitis Foundation of America. Jul 2014 - Jun 2017.

Epithelial Genes in Allergic Inflammation. Project 2 – Collaborating Investigator. National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAIDS). Sep 2006-Aug 2016.

Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant Ulcerative Colitis. Principal Investigator. National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK). Apr 2012-Mar 2016.

Margaret K. Hostetter, MD BK Rachford Professor and Chair, Department of Pediatrics

studies the pathogenesis of bloodstream infections caused by the yeast Candida albicans. Her work has highlighted the role of C. albicans in biofilms, activation of human T cells, and evasion of innate immune mechanisms. Her clinical research is focused on the medical evaluation of internationally adopted children.

513-636-4509 margaret.hostetter@cchmc.org

Shouxiong Huang, PhD Member, Immunology Graduate Program

investigates the activation and function of innate-like T cells in responses to vitamin-like and lipid antigens using metabolomic and biological approaches. The goal is to discover novel structures and presentation mechanisms of antigens that induce protective T cell responses and ultimately facilitate controlling immune disorders and environmental exposure.

513-558-7572 shouxiong.huang@uc.edu

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Shouxiong Huang, PhD

Member, Immunology Graduate Program

Academic Affiliations

Assistant Professor, UC Department of Environmental Health

Phone 513-558-7572

Email shouxiong.huang@uc.edu

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Biography

Dr. Huang’s studies have been focused on the activation and function of T cells in infectious and inflammatory diseases. During his postdoctoral training with Ted Hansen at Washington University, he started understanding the activation mechanism of innate-like T cells, specifically the mucosal-associated invariant T cells (MAIT) that are restricted by MHC class I like molecule MR1. He generated three major findings including the requirement of an antigen for MAIT cell activation (J Biol Chem, 2005), endocytic pathway of MAIT cell antigen loading (J Exp Med, 2008), and innate-like recognition of MR1 antigen complex by semi-invariant MAIT T cell receptor (PNAS, 2009). These findings supported the hypothesis that MAIT cells bear a rapid innate-like activation mechanism able to uniquely regulate mucosal diseases (Nat Immunol, 2007 review) and further inspired the discovery of MAIT cell protection against mycobacterial infection (Nat Immunol, 2010). As the lipid-responding T cells also show similar innate-like activation features, Dr. Huang’s additional training with Branch Moody at Harvard Medical School helped him establish a metabolomic platform and its applications to the antigens presented by MHC class I like CD1 proteins for the activation of lipid-responding T cells. These studies firstly revealed that the CD1b scaffold lipid diacylglycerol facilitates the presentation of the antigen mycobacterial glucose monomycolate to activate T cells from human tuberculosis (PNAS, 2011). Further collaboration using his metabolomic platform has discovered that mycobacterial and host lipid antigens were able to activate CD1c and CD1a-restricted T cells (J Exp Med, 2013, Nature Immunol, 2013).

Dr. Huang is extending the studies on the activation mechanisms and antigen structures of innate-like T cells particularly to the settings of mycobacterial infection, gut inflammation, and environmental exposure.

BS: Beijing University of Chinese Medicine, 1993.

PhD: The Ohio State University, 2003.

Postdoc: Washington University in St. Louis, 2003-2009.

Postdoc: Harvard Medical School, 2009-2011.

de Jong A, Cheng TY, Huang S, Gras S, Birkinshaw R, Kasmar A, van Rhijn I, Peña-Cruz V, Ruan DT, Altman JD, Rossjohn J, Moody DB. CD1a autoreactive T cells recognize natural skin oils that function as headless antigens. Nature Immunology. 2014;15(2):177-85.

Ly D, Kasmar AG, Cheng TY, de Jong A, Huang S, Roy S, Bhatt A, van Summeren RP, Altman JD, Jacobs Jr WR, Adams EJ, Minnaard AJ, Porcelli SA, Moody DB. CD1c tetramers detect ex vivo T cell responses to processed Mycobacterium phosphomycoketide antigens. Journal of Experimental Medicine. 2013;210(4):729-41.

Young MH, U'Ren L, Huang S, Mallevaey T, Scott-Browne J, Crawford F, Lantz O, Hansen TH, Kappler J, Marrack P, Gapin L. MAIT cell recognition of MR1 on bacterially infected and uninfected cells. PLOS ONE. 2013;8(1):e53789.

Huang S, Cheng TY, Young D, Layre E, Madigan C, Shires J, Cerundolo V, Altman JD, and Moody DB. Discovery of deoxyceramides and diacylglycerols as CD1b scaffold lipids among the diverse groove blocking lipids of the human CD1 system. Proc Natl Acad Sci USA. 2011;108(48):19335-19340.

Chua WJ, Yu L, Kim S, Myers N, Huang S, Fremont DH, Hansen TH. Endogenous MR1 is transiently expressed on the cell surface in a functional conformation capable of MAIT cell activation. J Immunol. 2011;186(8):4744-4750.

Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, Lévy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O. Antimicrobial activity of mucosal-associated invariant T cells. Nature Immunology. 2010;11(8):701-708.

Huang S, Martin E, Kim S, Yu L, Soudais C, Fremont DH, Lantz O, Hansen TH. MR1 antigen presentation to mucosal-associated invariant T cells was highly evolutionarily conserved. Proc Natl Acad Sci USA. 2009:106(20):8290-8295.

Huang S, Gilfillan S, Kim S, Thompson B, Wang X, Sant AJ, Fremont DH, Lantz O, and Hansen TH. MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells. Journal of Experimental Medicine. 2008;205(5):1201-1211.

Hansen TH, Huang S, Arnold PL, Fremont DH. Patterns of nonclassical MHC antigen presentation (Review). Nature Immunology. 2007;8(6):563-568.

Huang S, Sahin O, Zhang Q. Infection induced antibodies against the major outer membrane protein of Campylobacter jejuni mainly recognize conformational epitopes. FEMS Microbiology Letters. 2007;272(7):137-143.

Grants

Shouxiong Huang. Antigen metabolomics for mucosal-associated invariant T cells in tuberculosis. Principal Investigator. National Institute of Allergy and Infectious Diseases (NIAID). Dec 2014-Nov 2016.

Vivian Hwa, PhD Basic Research Director, Cincinnati Center for Growth Disorders

investigates the functional and cellular impacts of genetic defects identified in children with severe growth failure, who often present with a variety of co-morbidities, including immune deficiencies, insulin insensitivities, intellectual impairment, microcephaly. These pathophysiological mutations provide unique opportunities to delineate molecular mechanism(s) of actions and improve understanding of clinical phenotypes.
Visit the Dauber-Hwa Lab.

513-803-7337 vivian.hwa@cchmc.org

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Vivian Hwa, PhD

Basic Research Director, Cincinnati Center for Growth Disorders

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-7337

Email vivian.hwa@cchmc.org

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Visit the Dauber - Hwa Lab.

BS: University of Sydney, Sydney, Australia.

PhD: University of Illinois, Champaign-Urbana, IL.

Kern SL, Guevara-Aguirre J, Andrew S, Geng J, Guevara C, Guevara-Aguirre M, Guo M, Oddoux C, Shen Y, Zurita A, Rosenfeld RG, Ostrer H, Hwa V, Dauber A. A novel variant in CDKN1C is associated with intrauterine growth restriction, short stature, and early-adulthood onset diabetes. J Clin Endocrinol Metab. 2014 Oct;99(10):E2117-22.

Feigerlova E, Swinyard M, Andrew SF, Derr MA, Farnsworth J, Rosenfeld RG, Hwa V. A novel GHR intronic variant c.266+83G>T, activates a cryptic 5’ splice site causing severe GHR deficiency and classical GH insensitivity syndrome. Horm Res Paediatr. 2013;80(6):397-405.

Varco-Merth B, Feigerlová E, Shinde U, Rosenfeld RG, Hwa V, Rotwein P. Severe growth deficiency is associated with STAT5b mutations that disrupt protein folding and activity. Mol Endocrinol. 2013 Jan;27(1):150-61.

Dauber A, LaFranchi SH, Maliga Z, Lui JC, Moon JE, McDeed C, Henke K, Zonana J, Kingman GA, Pers TH, Baron J, Rosenfeld RG, Hirschhorn JN, Harris MP, Hwa V. Novel Microcephalic Primordial Dwarfism Disorder Associated with Variants in the Centrosomal Protein Ninein. J Clin Endocrinol Metab. 2012 Nov;97(11):E2140-51.

Scalia PA, Martinez AS, Feigerlova E, Bezrodnik L, Gaillard MI, Di Giovanni D, Ballerini MG, Jasper HG, Heinrich JJ, Fang P, Domené HM, Rosenfeld RG, Hwa V. A novel missense mutation in the SH2 domain of the STAT5B gene results in a transcriptionally inactive STAT5b associated with severe IGF-I deficiency, immune dysfunction, and lack of pulmonary disease. J Clin Endocrinol Metab. 2012 May;97(5):E830-9.

Derr MA, Aisenberg J, Fang P, Tenenbaum-Rakover Y, Rosenfeld RG, Hwa V. The growth hormone receptor (GHR) c.899dupC mutation functions as a dominant negative: insights into the pathophysiology of intracellular GHR defects. J Clin Endocrinol Metab. 2011 Nov;96(11):E1896-904.

Fang P, Kofoed EM, Little BM, Ross RJM, Frank, SJ, Hwa V, Rosenfeld RG. A mutant STAT5b, associated with growth hormone insensitivity and IGF-I deficiency, cannot function as a signal transducer or transcription factor. J Clin Endocrinol Metab. 2006 Apr; 91(4):1526-34.

Hwa V, Little B, Adiyaman P, Kofoed E, Pratt KL, Ocal G, Berberoglu M, Rosenfeld RG. Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. J Clin Endocrinol Metab. 2005 Jul;90(7):4260-6.

Hwa V, Little B, Kofoed EM, Rosenfeld RG. Transcriptional regulation of insulin-like growth factor-I (IGF-I) by interferon-gamma (IFN-γ) requires STAT-5b. J Biol Chem. 2004 Jan 23;279(4):2728-36.

Kofoed EM*, Hwa V*, Little B, Woods KA, Buckway CK, Tsubaki J, Pratt KL, Bezrodnik L, Jasper H, Tepper A, Heinrich JJ, Rosenfeld RG. Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med. 2003 Sep 18:349(12):1139-47. *co-first authors

Edith Janssen, PhD

focuses on mechanistic analysis and translational exploitation of the processes in dendritic cells that balance pro- and anti-inflammatory immune responses to self after cell death. Dr. Janssen aims at harnessing dendritic cells to develop effective autologous cancer vaccines. Her recent discovery (with Dr. Jonathan Katz) that dysregulation of such cells suggests a potential role for therapeutic modulation of these cells in autoimmune disease.
Visit the Janssen Lab.

513-803-1055 edith.janssen@cchmc.org

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Edith Janssen, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1055

Fax 513-636-5355

Email edith.janssen@cchmc.org

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Visit the Janssen Lab.

MS: Utrecht University, The Netherlands, 1995.

PhD: Utrecht University, The Netherlands, 1999.

Hennies CM, Reboulet RA, Garcia Z, Nierkens S, Wolkers MC, Janssen EM. Selective expansion of merocytic dendritic cells and CD8DCs confers anti-tumour effect of Fms-like tyrosine kinase 3-ligand treatment in vivo. Clin Exp Immunol. 2011 Jan 14.

Reboulet RA, Hennies CM, Garcia Z, Nierkens S, Janssen EM. Prolonged antigen storage endows merocytic dendritic cells with enhanced capacity to prime anti-tumor responses in tumor-bearing mice. J Immunol. 2010 Sep 15;185(6):3337-47.

Katz JD, Ondr JK, Opoka RJ, Garcia Z, Janssen EM. Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes. J Immunol. 2010 Aug 15;185(4):1999-2003.

Janssen EM, Lemmens EE, Gour N, Reboulet RA, Green DR, Schoenberger SP, Pinkoski MJ. Distinct roles of cytolytic effector molecules for antigen-restricted killing by CTL in vivo. Immunol Cell Biol. 2010 Oct;88(7):761-5.

Krebs P, Barnes MJ, Lampe K, Whitley K, Bahjat KS, Beutler B, Janssen E, Hoebe K. NK-cell-mediated killing of target cells triggers robust antigen-specific T-cell-mediated and humoral responses. Blood. 2009 Jun 25;113(26):6593-602.

Kim-Saijo M, Janssen EM, Sugie K. CD4 cell-secreted, posttranslationally modified cytokine GIF suppresses Th2 responses by inhibiting the initiation of IL-4 production. Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19402-7.

Hildeman D, Janssen E. IFN-gamma and self-absorbed CD4+ T cells: a regulatory double negative. Nat Immunol. 2008 Nov;9(11):1210-2.

Benedict CA, Loewendorf A, Garcia Z, Blazar BR, Janssen EM. Dendritic cell programming by cytomegalovirus stunts naïve T cell responses via the PD-L1/PD-1 pathway. J Immunol. 2008 180:4836-4847.

Mothé B, Stewart B, Oseroff C, Bui H, Stogiera S, Garcia Z, Dow C, Rodriguez-Carreno M, Kotturi M, Pasquetto V, Botten J, Crotty S, Janssen E, Buchmeier M, Sette A . Chronic LCMV infection actively down regulates CD4+ T-cell responses directed against a broad range of epitopes. J Immunol. 2007 179:1058-1067.

Benedict CA, Janssen EM. Immunosuppression, learning from the masters. ERCI. 2007 3:659-662P.

Michael B. Jordan, MD Member, Langerhans Cell Histiocytosis Center

specializes in caring for children with histiocytic disorders, primary immune deficiencies, or who are undergoing bone marrow transplantation. His laboratory focuses on understanding effector T cell function, immune regulation, and the pathogenesis of hemophagocytic lymphohistiocytosis. He is also conducting preclinical scientific studies in addition to a translational clinical trial.

513-636-7287 michael.jordan@cchmc.org

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Michael B. Jordan, MD

Member, Langerhans Cell Histiocytosis Center

Member, Division of Immunobiology

Member, Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-7287

Fax 513-803-1969

Email michael.jordan@cchmc.org

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Clinical

Histiocytic disorders: HLH and LCH

Research

Better understanding histiocytic disorders and developing novel therapies for them; regulation of the immune response; immunotherapy of cancer

MD: UT Southwestern, Dallas, TX, 1993.

Residency: Children's Hospital of Dallas, Dallas, TX, 1996.

Fellowship: The Children's Hospital, Denver, CO, 2002.

Certification: American Board of Pediatrics, 1996; Sub-board of Pediatric Heme/Onc, 2002.

Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, Mehta PA, Davies SM, Jordan MB, Bleesing JJ, Filipovich AH. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010 Dec 23;116(26):5824-31.

Mehta PA, Vinks AA, Filipovich A, Bleesing J, Jodele S, Jordan MB, Marsh R, Tarin R, Edwards S, Fearing D, Lawrence J, Davies SM. Alternate-day micafungin antifungal prophylaxis in pediatric patients undergoing hematopoietic stem cell transplantation: a pharmacokinetic study. Biol Blood Marrow Transplant. 2010 Oct;16(10):1458-62.

Marsh RA, Madden L, Kitchen BJ, Mody R, McClimon B, Jordan MB, Bleesing JJ, Zhang K, Filipovich AH. XIAP deficiency: a unique primary immunodeficiency best classified as X-linked familial hemophagocytic lymphohistiocytosis and not as X-linked lymphoproliferative disease. Blood. 2010 Aug 19;116(7):1079-82.

Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB, Bleesing JJ, Filipovich AH, Zhang K. STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. Pediatr Blood Cancer. 2010 Jul 15;55(1):134-40.

Lykens JE, Terrell CE, Zoller EE, Divanovic S, Trompette A, Karp CL, Aliberti J, Flick MJ, Jordan MB. Mice with a selective impairment of IFN-gamma signaling in macrophage lineage cells demonstrate the critical role of IFN-gamma-activated macrophages for the control of protozoan parasitic infections in vivo. J Immunol. 2010 Jan 15;184(2):877-85.

Lin AA, Tripathi PK, Sholl A, Jordan MB, Hildeman DA. Gamma interferon signaling in macrophage lineage cells regulates central nervous system inflammation and chemokine production. J Virol. 2009 Sep;83(17):8604-15.

Marsh RA, Villanueva J, Kim MO, Zhang K, Marmer D, Risma KA, Jordan MB, Bleesing JJ, Filipovich AH. Patients with X-linked lymphoproliferative disease due to BIRC4 mutation have normal invariant natural killer T-cell populations. Clin Immunol. 2009 Jul;132(1):116-23.

Marsh RA, Villanueva J, Zhang K, Snow AL, Su HC, Madden L, Mody R, Kitchen B, Marmer D, Jordan MB, Risma KA, Filipovich AH, Bleesing JJ. A rapid flow cytometric screening test for X-linked lymphoproliferative disease due to XIAP deficiency. Cytometry B Clin Cytom. 2009 Sep;76(5):334-44.

Jordan MB, Filipovich AH. Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step. Bone Marrow Transplant. 2008 Oct;42(7):433-7.

Wojciechowski S, Jordan MB, Zhu Y, White J, Zajac AJ, Hildeman DA. Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory. Eur J Immunol. 2006 Jul;36(7):1694-706.

Theodosia A. Kalfa, MD, PhD

focuses on the study of intracellular signals in erythropoiesis and mature red blood cells, specifically the signals conducted by Rho GTPases regulating terminal erythroid maturation and enucleation. Her lab also studies the role of Rac GTPases in generation of reactive oxygen species (ROS) within red blood cells from patients and animal models with sickle-cell disease along with the signaling mechanisms and consequences of increased ROS in sickle cells.
Visit the Kalfa Lab.

513-636-0989 theodosia.kalfa@cchmc.org

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Theodosia A. Kalfa, MD, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-0989

Fax 513-636-3549

Email theodosia.kalfa@cchmc.org

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Signaling in erythrocytes; erythropoiesis; sickle cell disease; reactive oxygen species

Visit the Kalfa Lab.

MD: Aristotle University Medical School, Thessaloniki, Greece, 1990.

PhD: Aristotle University Medical School, Thessaloniki, Greece, 1997.

Residency: University Of North Carolina, Chapel Hill, NC, 1999.

Fellowship: Duke University Medical Center, Durham, NC, 2003.

Certification: Hematology / oncology, American Board of Pediatrics, 2004; Pediatrics, American Board of Pediatrics, 2000; ECFMG Certification, 1995.

Licenses: Full and unrestricted medical license (OH Medical Board), 2003-present; full and unrestricted license of medical practice in Greece, 1990-present.

George A, Pushkaran S, Konstantinidis DG, Koochaki S, Malik P, Mohandas N, Zheng Y, Joiner CH, Kalfa TA. Erythrocyte NADPH oxidase activity modulated by Rac GTPases, PKC, and plasma cytokines contributes to oxidative stress in sickle cell disease. Blood. 2013 Mar 14;121(11):2099-107.

Konstantinidis DG, Pushkaran S, Johnson JF, Cancelas JA, Manganaris S, Harris CE, Williams DA, Zheng Y, Kalfa TA. Signaling and cytoskeletal requirements in erythroblast enucleation. Blood. 2012 Jun 21;119(25):6118-27.

Hammill AM, Risinger MA, Joiner CH, Keddache M, Kalfa TA. Compound heterozygosity for two novel mutations in the erythrocyte protein 4.2 gene causing spherocytosis in a Caucasian patient. Br J Haematol. 2011 Jan 31.

Kalfa TA. Anchoring at an island to relieve stress. Blood. 2011 Jan 20;117(3):748-9.

Mizukawa B, George A, Pushkaran S, Weckbach L, Kalinyak K, Heubi JE, Kalfa TA. Cooperating G6PD mutations associated with severe neonatal hyperbilirubinemia and cholestasis. Pediatr Blood Cancer. 2010 Oct 14.

Konstantinidis DG, George A, Kalfa TA. Rac GTPases in erythroid biology. Transfus Clin Biol. 2010 Sep;17(3):126-30.

Kalfa TA, Pushkaran S, Zhang X, Johnson JF, Pan D, Daria D, Geiger H, Cancelas JA, Williams DA, Zheng Y. Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen. Haematologica. 2010 Jan;95(1):27-35.

Mulloy JC, Cancelas JA, Filippi MD, Kalfa TA, Guo F, Zheng Y. Rho GTPases in hematopoiesis and hemopathies. Blood. 2010 Feb 4;115(5):936-47.

Wang D, Zhang W, Kalfa TA, Grabowski G, Davies S, Malik P, Pan D. Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19958-63.

Daria D, Filippi MD, Knudsen ES, Faccio R, Li Z, Kalfa T, Geiger H. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood. 2008 Feb 15;111(4):1894-902.

Grants

Rho GTPases in Terminal Erythroid Maturation. Principal Investigator. NIH/NHLBI. Sep 2012-Jun 2016. #1R01HL116352.

Cincinnati Center of Excellence in Hemoglobinopathies Research. Co-investigator. NIH/NHLBI. Aug 2013–May 2018. # U01 HL117709.

Jonathan D. Katz, PhD

is working to understand the role that autoreactive T lymphocytes play in the Immunopathogenesis of type 1 diabetes, the most common pediatric autoimmune disease. Major focuses include defining: (a) the control of autoreactive T cells via central and peripheral tolerance; (b) the role NKT cells play in regulating autoreactive T cells; and (c) the role dendritic cells play in activating and regulating autoreactive T cells in type 1 diabetes.

513-636-5306 jonathan.katz@cchmc.org

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Jonathan D. Katz, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-5306

Fax 513-636-5355

Email jonathan.katz@cchmc.org

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Clinical

T cells; MHC, beta cell death; islet antigens

Research

Immunology; autoimmunity; type 1 diabetes

Biography

Jonathan D. Katz, PhD, focuses on autoimmune diabetes research. Autoimmune diabetes, also known as type 1 diabetes (T1D), is the most common pediatric autoimmune disease. Roughly 1/250 individuals develop T1D in the United States.There is currently no cure for T1D and the only treatment is daily exogenous insulin replacement therapy. Many T1D patients eventually develop secondary complications, such as hearth disease, blindness, peripheral neuropathy and renal failure.

Dr. Katz's work focuses on the role that autoreactive T lymphocytes play in the disease process. His lab is interested in (1) the control of autoreactive T cells via central and peripheral tolerance, (2) the role NKT cells play in regulating autoreactive T cells, and (3) the role dendritic cells play in activating and regulating autoreactive T cells in T1D.

Most of his work uses the non-obese diabetic (NOD) mouse strain that spontaneously develops T1D with remarkable similarity to the T1D seen in human patients. The availability of the NOD strain has allowed the lab to take a modern, reductionist molecular and cellular immunology approach to understanding the mechanism(s) and genetics underlying T1D susceptibility and disease progression. Dr. Katz's lab makes extensive use of knockout, transgenic, regulated gene expression, targeted ablation, cell transfer and genomic studies the progression and regulation of T1D in the NOD mouse.

BS: University of California, Los Angeles, CA, 1984.

PhD: University of California, Los Angeles, CA, 1990.

Post-Doctoral Fellow: Université Louis Pasteur, Strasbourg, France, 1990-1995.

Katz JD, Ondr JK, Opoka RJ, Garcia Z, Janssen EM. Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes. J Immunol. 2010 Aug 15;185(4):1999-2003.

Pang S, Zhang L, Wang H, Yi Z, Li L, Gao L, Zhao J, Tisch R, Katz JD, Wang B. CD8(+) T cells specific for beta cells encounter their cognate antigens in the islets of NOD mice. Eur J Immunol. 2009 Oct;39(10):2716-24.

Saxena V, Ondr JK, Magnusen AF, Munn DH, Katz JD. The countervailing actions of myeloid and plasmacytoid dendritic cells control autoimmune diabetes in the nonobese diabetic mouse. J Immunol. 2007 Oct 15;179(8):5041-53.

Wojciechowski S, Tripathi P, Bourdeau T, Acero L, Grimes HL, Katz JD, Finkelman FD, Hildeman DA. Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis. J Exp Med. 2007 Jul 9;204(7):1665-75.

Cain JA, Smith JA, Ondr JK, Wang B, Katz JD. NKT cells and IFN-gamma establish the regulatory environment for the control of diabetogenic T cells in the nonobese diabetic mouse. J Immunol. 2006 Feb 1;176(3):1645-54.

Vukkadapu SS, Belli JM, Ishii K, Jegga AG, Hutton JJ, Aronow BJ, Katz JD. Dynamic interaction between T cell-mediated beta-cell damage and beta-cell repair in the run up to autoimmune diabetes of the NOD mouse. Physiol Genomics. 2005 Apr 14;21(2):201-11.

Hutton JJ, Jegga AG, Kong S, Gupta A, Ebert C, Williams S, Katz JD, Aronow BJ. Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system. BMC Genomics. 2004 Oct 25;5(1):82.

Kenneth M. Kaufman, PhD

investigates the genetics of complex and rare disorders using genotyping and next-generation DNA technologies. The goal of his research is to identify the underling mechanisms and genetics that lead to complex diseases such as systemic lupus erythematosus.

513-803-5385 kenneth.kaufman@cchmc.org

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Kenneth M. Kaufman, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-5385

Email kenneth.kaufman@cchmc.org

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Genetics; bio-informatics

Biography

A large portion of Dr. Kaufman's research career has been on the genetics of systemic lupus erythematsus. Their work has screened 10's of thousands of lupus cases and controls with millions of polymorphic markers. This work has results in the identification, replication and/or fine mapping of over 70 genetic associations with systemic lupus erythematsus.

Recently, they have taken advantage of next generation DNA sequencing to identify variants that directly cause disease. They have developed a number of bioinformatic pipelines that can be applied to any phenotype. These automated pipelines are part of the Cincinnati Analytical Suite for Sequencing Informatics (CASSI) which has been applied to more than 20 different diseases and provides a list of candidate causative variants that lead to disease.

PhD: University of South Carolina, Columbia, SC, 1991.

Patel ZH, Kottyan LC, Lazaro S, Williams MS, Ledbetter DH, Tromp H, Rupert A, Kohram M, Wagner M, Husami A, Qian Y, Valencia CA, Zhang K, Hostetter MK, Harley JB, Kaufman KM. The struggle to find reliable results in exome sequencing data: filtering out Mendelian errors. Front Genet. 2014 Feb 12;5:16.

Kaufman KM, Linghu B, Szustakowski JD, Husami A, Yang F, Zhang K, Filipovich AH, Fall N, Harley JB, Nirmala NR, Grom AA. Whole-exome sequencing reveals overlap between macrophage activation syndrome in systemic juvenile idiopathic arthritis and familial hemophagocytic lymphohistiocytosis. Arthritis Rheumatol. 2014 Dec;66(12):3486-95.

Kottyan LC, Zoller EE, Bene J, Lu X, Kelly JA, Rupert AM, Lessard CJ, Vaughn SE, Marion M, Weirauch MT, Namjou B, Adler A, Rasmussen A, Glenn S, Montgomery CG, Hirschfield GM, Xie G, Coltescu C, Amos C, Li H, Ice JA, Nath SK, Mariette X, Bowman S; UK Primary Sjögren's Syndrome Registry, Rischmueller M, Lester S, Brun JG, Gøransson LG, Harboe E, Omdal R, Cunninghame-Graham DS, Vyse T, Miceli-Richard C, Brennan MT, Lessard JA, Wahren-Herlenius M, Kvarnström M, Illei GG, Witte T, Jonsson R, Eriksson P, Nordmark G, Ng WF; UK Primary Sjögren's Syndrome Registry, Anaya JM, Rhodus NL, Segal BM, Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, Bae SC, Boackle SA, Criswell LA, Gilkeson G, Kamen DL, Jacob CO, Kimberly R, Brown E, Edberg J, Alarcón GS, Reveille JD, Vilá LM, Petri M, Ramsey-Goldman R, Freedman BI, Niewold T, Stevens AM, Tsao BP, Ying J, Mayes MD, Gorlova OY, Wakeland W, Radstake T, Martin E, Martin J, Siminovitch K, Moser Sivils KL, Gaffney PM, Langefeld CD, Harley JB, Kaufman KM. The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share. Hum Mol Genet. 2015 Jan 15;24(2):582-96.

Kaufman KM, Zhao J, Kelly JA, Hughes T, Adler A, Sanchez E, Ojwang JO, Langefeld CD, Ziegler JT, Williams AH, Comeau ME, Marion MC, Glenn SB, Cantor RM, Grossman JM, Hahn BH, Song YW, Yu CY, James JA, Guthridge JM, Brown EE, Alarcón GS, Kimberly RP, Edberg JC, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Anaya JM, Boackle SA, Stevens AM, Freedman BI, Criswell LA, Pons Estel BA; Argentine Collaborative Group, Lee JH, Lee JS, Chang DM, Scofield RH, Gilkeson GS, Merrill JT, Niewold TB, Vyse TJ, Bae SC, Alarcón-Riquelme ME; BIOLUPUS network, Jacob CO, Moser Sivils K, Gaffney PM, Harley JB, Sawalha AH, Tsao BP. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups. Ann Rheum Dis. 2013 Mar;72(3):437-44.

Raphael Kopan, PhD Director, Division of Developmental Biology

and his lab have the long-term goal of organogenesis in vitro. They focus their efforts on Notch signaling as their lead into mechanistic understanding of tissue diversity using genetic engineering, embryology and single cell profiling. They interrogate the mouse embryo to address critical questions regarding the circuit logic of Notch signaling in mammalian organogenesis and its integration in larger signaling context.

Visit the Kopan Lab.

513-636-1299

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Raphael Kopan, PhD

Director, Division of Developmental Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1299

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Notch signaling; kidney organogenesis; skin organogenesis; TSLP signaling in cancer

Visit the Kopan Lab.

Biography

Raphael Kopan, PhD, who is a professor of developmental biology at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine, has carried out seminal work in the field of Notch biology. This work has, and continues to have, an enormous impact on our understanding of normal tissue development and renewal, Alzheimer's disease and cancer-related research. In deciphering the mode of Notch activation and demonstrating the use of inhibitors to modulate Notch activity, Dr. Kopan's work laid the groundwork for the therapeutic use of γ-secretase inhibitors in the treatment of cancers, currently in clinical trials. His current interests in organogenesis are focused on two modular organs - skin and kidney - in which his group is trying to understand how interplay among the same seven pathways results in activation of distant programs. Dr. Kopan's work has resulted in 120 scientific articles as of 2013. He is the co-inventor of one patent, and he has served on scientific advisory boards as well as being a consultant to the pharmaceutical industry.

BS, MsC: Department of Zoology, Tel-Aviv University, Israel.

PhD: Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL.

Post-doctoral training : The Fred Hutchinson Cancer Research Center, Seattle, WA.

Chen S, Brunskill EW, Potter SS, Dexheimer PJ, Salomonis N, Aronow BJ, Hong CI, Zhang T, Kopan R. Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan. Developmental Cell. 2015;35:49-62.

Hass MR, Liow HH, Chen X, Sharma A, Inoue YU, Inoue T, Reeb A, Martens A, Fulbright M, Raju S, Stevens M, Boyle S, Park JS, Weirauch MT, Brent MR, Kopan R. SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers. Molecular Cell. 2015;9(4):685-697.

Demitrack ES, Gifford GB, Keeley TM, Carulli AJ, VanDussen KL, Thomas D, Giordano TJ, Liu Z, Kopan R, Samuelson LC. Notch signaling regulates gastric antral LGR5 stem cell function. EMBO J. 2015 Aug 12.

Liu Z, Brunskill E, Varnum-Finney B, Zhang C, Zhang A, Jay PY, Bernstein I, Morimoto M, Kopan R. The intracellular domains of Notch1 and 2 are functionally equivalent during development and carcinogenesis. Development. 2015;142:2452-2463.

Liu Z, Brunskill E, Boyle S, Chen S, Turkoz M, Guo Y, Grant R, Kopan R. Second-generation Notch1 activity-trap mouse line (N1IP::CreHI) provides a more comprehensive map of cells experiencing Notch1 activity. Development. 2015 Mar 15;142(6):1193-202.

Demehri S, Yockey LJ, Visness CM, Jaffee KF, Turkoz A, Wood RA, O'Connor GT, Kattan M, Gern JE, Gergen PJ, Holtzman M, Bloomberg G, Kopan R. Circulating TSLP associates with decreased wheezing in non-atopic preschool children: Data from the URECA birth cohort. Clin Exp Allergy. 2014 Jun;44(6):851-7.

Zhao ZQ, Huo FQ, Jeffry J, Hampton L, Demehri S, Kim S, Liu XY, Barry DM, Wan L, Liu ZC, Li H, Turkoz A, Ma K, Cornelius LA, Kopan R, Battey JF Jr, Zhong J, Chen ZF. Chronic itch development in sensory neurons requires BRAF signaling pathways. J Clin Invest. 2013 Nov;123(11):4769-80.

Chillakuri CR, Sheppard D, Ilagan MX, Holt LR, Abbott F, Liang S, Kopan R, Handford PA, Lea SM. Structural analysis uncovers lipid-binding properties of notch ligands. Cell Rep. 2013 Nov 27;5(4):861-7.

Boyle SC1, Liu Z, Kopan R. Notch signaling is required for the formation of mesangial cells from a stromal mesenchyme precursor during kidney development. Development. 2014 Jan;141(2):346-54.

Satpathy AT, Briseño CG, Lee JS, Ng D, Manieri NA, Kc W, Wu X, Thomas SR, Lee WL, Turkoz M, McDonald KG, Meredith MM, Song C, Guidos CJ, Newberry RD, Ouyang W, Murphy TL, Stappenbeck TS, Gommerman JL, Nussenzweig MC, Colonna M, Kopan R, Murphy KM. Notch2-dependent classical dendritic cells orchestrate intestinal immunity to attaching-and-effacing bacterial pathogens. Nat Immunol. 2013 Sep;14(9):937-48.

Leah C. Kottyan, PhD

studies the molecular and immunological mechanisms driving the statistical association of genetic variants with systemic lupus erythematosus and eosinophilic esophagitis. The goal of her research is to refine the statistical analysis of genetic data while using analytical and biological tools to predict and confirm genetic variant-dependent differences that affect gene expression, cell function, and disease risk.

513-636-1316 leah.kottyan@cchmc.org

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Leah C. Kottyan, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-1316

Email leah.kottyan@cchmc.org

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Genetic basis of lupus; genetic basis of eosinophilic esophagitis; immunological mechanisms mediating genetic association with disease

Visit the Kottyan Lab.

Biography

For the past decade, many geneticists have approached genetic analysis with the idea that they simply need to increase statistical power by enlarging the sample size (e.g. ~100,000 person height GWAS) and assess enough loci in order to find the “genes” associated with a disease. Unfortunately, clinicians can do relatively little with this type of correlative genetic information. Dr. Kottyan recently lead a genome-wide association analysis of eosinophilic esophagitis in which they went beyond the identification of nine new risk loci and identified the molecular, tissue-specific mechanisms through which genetic variants at the CAPN14 locus increase risk of disease.

During her post-doctoral fellowship, she optimized statistical modeling strategies using genetic data from large multi-ancestral cohorts to identify candidate genetic causal variants through complementary frequentist and Bayesian approaches. In genetic analysis, it is easy and even tempting to make a story out of a genetic variant that seems important. Using two types of statistical analyses on multiple cohorts of different ancestry helps to avoid the misplaced attribution of causality. Instead, Dr. Kottyan’s group develops a short list of variants that are most statistically likely to be causal before they start biological or functional analysis. Once identified, the group predicts and confirms biological phenotypes that are affected by the risk variants.

BA: Chemistry and Cell Biology, Huntingdon College, Montgomery, AL, 2005.

PhD: Immunobiology, University of Cincinnati, Cincinnati, OH, 2010.

Lu X, Zoller EE, Weirauch M, Wu X, Namjou-Khales B, Williams A, Ziegler J, Comeau MR, Marion M, Glenn S, Adler A, Shen N, Nath SK, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown E, Gilkeson G, Alarcon GS, Reveille JD, Anaya JM, James JA, Sivils K, Criswell LA, Vila LM, Alarcon-Riquelme M, Petri M, Scofield RH, Kimberly R, Ramsey-Goldman R, Joo YB, Choi J, Bae SC, Boackle SA, Cunninghame-Graham DS, Vyse T, Guthridge JM, Gaffney PM, Langefeld CD, Kelly J, Greis K, Kaufman K, Harley JB, Kottyan L. Lupus risk-variant increases pSTAT1 binding and decreases ETS1 expression. American journal of human genetics. 2015.

Vaughn SE, Foley C, Lu X, Patel ZH, Zoller EE, Magnusen AF, Williams AH, Ziegler JT, Comeau ME, Marion MC, Glenn SB, Adler A, Shen N, Nath S, Stevens AM, Freedman BI, Tsao BP, Jacob CO, Kamen DL, Brown EE, Gilkeson GS, Alarcón GS, Reveille JD, Anaya J-M, James JA, Moser KL, Criswell LA, Vilá LM, Alarcón-Riquelme ME, Petri M, Scofield RH, Kimberly RP, Ramsey-Goldman R, Binjoo Y, Choi J, Bae S-C, Boackle SA, Vyse TJ, Guthridge JM, Namjou B, Gaffney PM, Langefeld CD, Kaufman KM, Kelly JA, Harley ITW, Harley JB, Kottyan LC. Lupus risk variants in the PXK locus alter B-cell receptor internalization. Frontiers in Genetics. 2015 Jan 8;5:450.

Kottyan LC, Weirauch MT, Rothenberg ME. Making it Big in Allergy. J Allergy Clin Immunol. 2015 Jan;135(1):43-5.

Makashir SB, Kottyan LC, Weirauch MT. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing Proceedings. 2015.

Brungs L, Lele A, Kottyan L, Levy B, Moncrieffe H. Genetic Basis of Rheumatic Diseases and the Importance of GWAS in Paediatric Rheumatology. Annals of Pediatric Rheumatology. 2015;3(3):105-115.

Verma SS, de Andrade M, Tromp G, Kuivaniemi H, Pugh E, Namjou-Khales B, Mukherjee S, Jarvik GP, Kottyan LC, Burt A, Bradford Y, Armstrong GD, Derr K, Crawford DC, Haines JL, Li R, Crosslin D, Ritchie MD. Imputation and quality control steps for combining multiple genome-wide datasets. Frontiers in Genetics. 2014 Dec 11;5:370.

Kottyan LC, Zoller EE, Bene J, Lu X, Kelly JA, Rupert AM, Lessard CJ, Vaughn SE, Marion M, Weirauch MT, Namjou B, Adler A, Rasmussen A, Glenn S, Montgomery CG, Hirschfield GM, Xie G, Coltescu C, Amos C, Li H, Ice JA, Nath SK, Mariette X; Simon Bowman for UK primary Sjögren's syndrome registry, Rischmueller M, Lester S, Brun JG, Gøransson LG, Harboe E, Omdal R, Cunninghame-Graham DS, Vyse T, Miceli-Richard C, Brennan MT, Lessard JA, Wahren-Herlenius M, Kvarnström M, Illei GG, Witte T, Jonsson R, Eriksson P, Nordmark G; Wan-Fai Ng for UK primary Sjögren's syndrome registry, Anaya JM, Rhodus NL, Segal BM, Merrill JT, James JA, Guthridge JM, Scofield RH, Alarcon-Riquelme M, Bae SC, Boackle SA, Criswell LA, Gilkeson G, Kamen DL, Jacob CO, Kimberly R, Brown E, Edberg J, Alarcón GS, Reveille JD, Vilá LM, Petri M, Ramsey-Goldman R, Freedman BI, Niewold T, Stevens AM, Tsao BP, Ying J, Mayes MD, Gorlova OY, Wakeland W, Radstake T, Martin E, Martin J, Siminovitch K, Moser Sivils KL, Gaffney PM, Langefeld CD, Harley JB, Kaufman KM. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet. 2014 Jan 15;24(2):582-98.

Namjou B, Ni Y, Harley IT, Chepelev I, Cobb B, Kottyan LC, Gaffney PM, Guthridge JM, Kaufman K, Harley JB. The effect of inversion at 8p23 on BLK association with lupus in Caucasian population. PLoS One. 2014 Dec 29;9(12):e115614.

Alexander ES, Martin LJ, Collins MH, Kottyan LC, Sucharew H, He H, Mukkada VA, Succop PA, Abonia JP, Foote H, Eby MD, Grotjan TM, Greenler AJ, Dellon ES, Demain JG, Furuta GT, Gurian LE, Harley JB, Hopp RJ, Kagalwalla A, Kaul A, Nadeau KC, Noel RJ, Putnam PE, von Tiehl KF, Rothenberg ME. Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis. J Allergy Clin Immunol. 2014 Nov;134(5):1084-1092.

Fardo DW, Zhang X, Ding L, He H, Kurowski B, Alexander ES, Baye TM, Pilipenko V, Kottyan L, Nandakumar K, Martin LJ. On Family-based Genome-wide Association Studies with Large Pedigrees: Observations and Recommendations. BMC Proceedings. 2014;8(1):s26-s26.

Ashish R. Kumar, MD, PhD Director, Langerhans Cell Histiocytosis Center

is a pediatric hematologist/oncologist whose lab is investigating the biology childhood cancers and blood diseases. The current focus of research in the lab is on infant leukemia and LCH.
Visit the Kumar Lab.

513-803-1631 ashish.kumar@cchmc.org

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Ashish R. Kumar, MD, PhD

Director, Langerhans Cell Histiocytosis Center

Director, Hematology/Oncology Fellowship Program

Member, Hematological Malignancy Program

Member, Division of Bone Marrow Transplantation and Immune Deficiency, Cancer and Blood Diseases Institute

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-1631

Fax 513-636-3549

Email ashish.kumar@cchmc.org

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Clinical

Childhood cancer and blood disorders; immune deficiency

Research

Leukemia biology; cancer biology

Visit the Kumar Lab.

Biography

Visit the HLH Center of Excellence.

Dr. Kumar received his medical degree from L.T.M. Medical College, Mumbai, India, his PhD in anatomy and cell biology from the University of Iowa, pediatric residency training at the Mayo Clinic and fellowship in pediatric hematology / oncology / BMT at the University of Minnesota. He was appointed to the faculty of the University of Minnesota in the Department of Pediatrics where he was a member of the programs in pediatric leukemia and global pediatrics. He is currently an associate professor of pediatrics in the Division of Bone Marrow Transplantation and Immune Deficiency at Cincinnati Children's within the University of Cincinnati College of Medicine. Dr. Kumar’s laboratory is engaged in researching the biology of infant leukemia. Discoveries made in his laboratory have significantly enhanced the current understanding of leukemia. Dr. Kumar is also active in education. He has delivered invited lectures and grand round presentations on various topics.

Learn more about the 700 Miles to Hope Bike Ride.

MD: LTM Medical College, Mumbai, India.

Residency: Mayo Clinic, Rochester, MN.

Fellowship: University of Minnesota, Minneapolis, MN.

PhD: University of Iowa, Iowa City, IA.

Certification: General Pediatrics; Pediatric Hematology/Oncology Subspecialty.

Licenses: State of Ohio; State of Minnesota.

Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kütükcüler N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal Ö, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Hönig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Dückers G, Al-Herz W, Pai SY, Geha R, Notheis G, Schwarze CP, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH; inborn errors working party of EBMT. DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients. J Clin Immunol. 2015 Feb;35(2):189-98.

Roychoudhury J, Clark JP, Gracia-Maldonado G, Unnisa Z, Wunderlich M, Link KA, Dasgupta N, Aronow B, Huang G, Mulloy JC, Kumar AR. MEIS1 regulates an HLF-oxidative stress axis in MLL-fusion gene leukemia. Blood. 2015;125(16):2544-52.

Marsh RA, Rao MB, Gefen A, Bellman D, Mehta PA, Khandelwal P, Chandra S, Jodele S, Myers KC, Grimley M, Dandoy C, El-Bietar J, Kumar AR, Leemhuis T, Zhang K, Bleesing JJ, Jordan MB, Filipovich AH, Davies SM. Experience with Alemtuzumab, Fludarabine, and Melphalan Reduced-Intensity Conditioning Hematopoietic Cell Transplantation in Patients with Nonmalignant Diseases Reveals Good Outcomes and That the Risk of Mixed Chimerism Depends on Underlying Disease, Stem Cell Source, and Alemtuzumab Regimen. Biol Blood Marrow Transplant. 2015 Aug;21(8):1460-70.

Cai X, Gao L, Teng L, Ge J, Oo ZM, Kumar AR, Gilliland DG, Mason PJ, Tan K, Speck NA. Runx1 Deficiency Decreases Ribosome Biogenesis and Confers Stress Resistance to Hematopoietic Stem and Progenitor Cells. Cell Stem Cell. 2015 Jul;pii:S1934-5909(15)00262-3.

Karkare S, Chhipa RR, Anderson J, Liu X, Henry H, Gasilina A, Nassar N, Roychoudhury J, Clark JP, Kumar A, Pauletti GM, Ghosh PK, Dasgupta B. Direct inhibition of retinoblastoma phosphorylation by nimbolide causes cell-cycle arrest and suppresses glioblastoma growth. Clin Cancer Res. 2014 Jan;20(1):199-212.

Khandelwal P, Lawrence J, Filipovich AH, Davies SM, Bleesing JJ, Jordan MB, Mehta P, Jodele S, Grimley MS, Kumar A, Myers K, Marsh RA. The successful use of alemtuzumab for treatment of steroid-refractory acute graft-versus-host disease in pediatric patients. Pediatr Transplant. 2014 Feb;18(1):94.

Liu X, Chhipa RR, Pooya S, Wortman M, Yachyshin S, Chow LM, Kumar A, Zhou X, Sun Y, Quinn B, McPherson C, Warnick RE, Kendler A, Giri S, Poels J, Norga K, Viollet B, Grabowski GA, Dasgupta B. Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci USA. 2014 Jan;111(4):E435-44.

Zhou J, Wu J, Li B, Liu D, Yu J, Yan X, Zheng S, Wang J, Zhang L, Zhang L, He F, Li Q, Chen A, Zhang Y, Zhao X, Guan Y, Zhao X, Yan J, Ni J, Nobrega MA, Löwenberg B, Delwel R, Valk PJ, Kumar A, Xie L, Tenen DG, Huang G, Wang QF. PU.1 is Essential for MLL Leukemia Partially via Crosstalk with the MEIS/HOX Pathway. Leukemia. 2014 Jul;28(7):1436-48.

Jing H, Zhang Q, Zhang Y, Hill BJ, Dove CG, Gelfand EW, Atkinson TP, Uzel G, Matthews HF, Mustillo PJ, Lewis DB, Kavadas FD, Hanson IC, Kumar AR, Geha RS, Douek DC, Holland SM, Freeman AF, Su HC. Somatic reversion in dedicator of cytokinesis 8 immunodeficiency modulates disease phenotype. The Journal of allergy and clinical immunology. 2014 Jun;133(6):1667-75.

Marsh RA, Rao K, Satwani P, Lehmberg K, Müller I, Li D, Kim MO, Fischer A, Latour S, Sedlacek P, Barlogis V, Hamamoto K, Kanegane H, Milanovich S, Margolis DA, Dimmock D, Casper JT, Douglas DN, Amrolia PJ, Veys P, Kumar AR, Jordan BM, Bleesing J, Filipovich A. Allogeneic Hematopoietic Cell Transplantation for XIAP Deficiency: An International Survey Reveals Poor Outcomes. Blood. 2013 Feb 7;121(6):877-83.

Grants

Role of MEIS1 in hematopoiesis and hematopoietic transformation. Principal Investigator. National Institutes of Health/National Heart, Lung, and Blood Institute. Jul 2012-Jun 2017.

Novel therapeutics of targeting mTOR pathway in T-cell leukemia. Co-investigator. National Institutes of Health/National Cancer Institute. Jul 2015-Jun 2017.

Ian P. Lewkowich, PhD

investigates the factors that drive the development of severe allergic asthma, with a particular focus on the molecular mechanisms through which Th17 cytokines enhance IL-13 signaling, the regulation of the asthmatic response through the PD-1/PD-L axis and the mechanisms of the well-described maternal influence in inherited asthma risk.
Visit the Lewkowich Lab.

513-636-3999 ian.lewkowich@cchmc.org

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Ian P. Lewkowich, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-3999

Email ian.lewkowich@cchmc.org

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Immunology; asthma

Visit the Lewkowich Lab.

Biography

While Th2 immune responses are central to disease pathology in allergic asthma, there is a growing understanding that the Th2 paradigm is not sufficient to explain the entire spectrum of disease severity. Indeed, there is growing belief that severe disease may be driven by a different process than mild to moderate disease.

Using a mouse model of allergic asthma in which one strain develops a phenotype characteristic of mild asthma (C3H/HeJ), and others develop a phenotype characteristic of severe disease (A/J), we have identified several novel mechanisms through which asthma severity is regulated. We have found that the development of severe allergic asthma is associated with a limited capacity of Tregs to limit pulmonary dendritic cell activity, enhanced capacity for antigen uptake by pulmonary myeloid dendritic cells, and the development of a mixed Th2/Th17 immune response. In contrast, C3H mice demonstrate increased Treg activity, preferential antigen uptake by pulmonary plasmacytoid dendritic cells, and an exclusively Th2-biased immune response. We are presently using the A/J versus C3H/HeJ mouse model of allergic asthma to tease out the mechanisms responsible the development of severe allergic asthma.

PhD: University of Manitoba, Winnipeg, Canada, 2004.

Lewkowich IP, Fox JG Perkins C, Lewis L, Finkelman FD Smith DE, Bryce PJ, Kurt-Jones EA, Wang TC, Sivaprasad U, Hershey GK, Herbert DR. Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection. J Exp Med. 2012;209(3):607-22.

Lufti R, Ledford JR, Zhou P, Lewkowich IP, Page K. Dendritic Cell-Derived Tumor Necrosis Factor α Modifies Airway Epithelial Cell Responses. J Innate Immun. 2012;4(5-6):542-52.

Lewkowich IP, Lajoie S, Stoffers SL, Suzuki Y, Richgels PK, Dienger K, Sproles AA, Yagita H, Hamid Q, Wills-Karp M. PD-L2 modulates asthma severity by directly decreasing dendritic cell IL-12 production. Mucosal Immunol. 2012.

Stefater JA, Lewkowich IP, Rao S, Ajima R, Mariggi G, Wills-Karp M, Pollard J, Yamaguchi T, McMahon AP, Ferrara N, Gerhardt H, Lang RA. Microglial Wnt ligands suppress retinal angiogenesis via activation of the VEGF inhibitor Flt1. Nature. 2011;474(7352):511-515.

Lewkowich IP, Day SB, Ledford JR, Zhou P, Dienger K, Wills-Karp M, Page K. Protease-activated receptor 2 activation of myeloid dendritic cells regulates allergic airway inflammation. Respir Res. 2011;(12):122.

Lewkowich IP1, Lajoie S1, Suzuki Y, Clark JR, Sproles AA, Dienger K, Budelsky A, and Wills-Karp M, Complement-mediated regulation of the IL-17A axis is a central genetic determinant of the severity of experimental allergic asthma. Nat Immunol. 2010;(10):928-935.

Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich IP, Wills-Karp M and Whitsett JA. Foxa2 programs Th2 cell-mediated innate immunity in the developing lung. J Immunol. 2010;(184):6133-6141.

Lewkowich IP, Lajoie S, Dienger K, Herman NS, Sproles AA, and Wills-Karp M. Enhanced allergen uptake, activation, and IL-23 production by pulmonary myeloid DCs drives airway hyperresponsiveness in asthma-susceptible mice. PLoS ONE. 2008;(3):e3879.

Köhl J, Baelder R, Lewkowich IP, Pandey MK, Hawlisch H, Wang L, Best J, Herman NS, Sproles AA, Zwirner J, Whitsett JA, Gerard C, Sfyroera G, Lambris JD, and Wills-Karp M. A regulatory role for the C5a anaphylotoxin on type 2 immunity in asthma. J Clin Invest. 2006;(116):783-796.

Lewkowich IP, Herman NS, Schleifer KW, Dance MP, Chen BL, Dienger KM, Sproles AA, Shah JS, Köhl J, Belkaid Y, and Wills-Karp M. CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function. J Exp Med. 2005;(202):1549-1561.

Punam Malik, MD Marjory J. Johnson Chair of Gene and Cell Therapy

works to correct the gene responsible for sickle cell anemia. One of the lab’s major projects uses gene therapy to treat sickle cell disease. The lab is also interested in gene therapy for other diseases. She has developed various methods for delivering corrective genes to cells, improving methods for gene therapy in general.

513-636-1333 punam.malik@cchmc.org

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Punam Malik, MD

Marjory J. Johnson Chair of Gene and Cell Therapy

Director, Cincinnati Comprehensive Sickle Cell Program

Program Leader, Hematology and Gene Therapy Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-1333

Fax 513-636-1330

Email punam.malik@cchmc.org

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MBBS: University of Delhi, New Delhi, India, 1985.

MD: University of Delhi, New Delhi, India, 1989.

MS: University of Maryland, Baltimore, MD, 1991.

Fellowship: Children's Hospital Los Angeles, University of Southern California, 1995.

Arumugam P, Malik P. Genetic therapy for beta-thalassemia: from the bench to the bedside. Hematology Am Soc Hematol Educ Program. 2010;2010:445-50.

Perumbeti A, Malik P. Therapy for beta-globinopathies: a brief review and determinants for successful and safe correction. Ann N Y Acad Sci. 2010 Aug;1202:36-44. Review.

Perumbeti A, Malik P. Genetic correction of sickle cell anemia and beta-thalassemia: progress and new perspective. Scientific World Journal. 2010 Apr 13;10:644-54. Review.

Sundaram N, Tailor A, Mendelsohn L, Wansapura J, Wang X, Higashimoto T, Pauciulo MW, Gottliebson W, Kalra VK, Nichols WC, Kato GJ, Malik P. High levels of placenta growth factor in sickle cell disease promote pulmonary hypertension. Blood. 2010 Jul 8;116(1):109-12.

Wang D, Zhang W, Kalfa TA, Grabowski G, Davies S, Malik P, Pan D. Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19958-63.

Arumugam PI, Urbinati F, Velu CS, Higashimoto T, Grimes HL, Malik P. The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity. PLoS One. 2009 Sep 10;4(9):e6995.

Arumugam PI, Higashimoto T, Urbinati F, Modlich U, Nestheide S, Xia P, Fox C, Corsinotti A, Baum C, Malik P. Genotoxic potential of lineage-specific lentivirus vectors carrying the beta-globin locus control region. Mol Ther. 2009 Nov;17(11):1929-37.

Perumbeti A, Higashimoto T, Urbinati F, Franco R, Meiselman HJ, Witte D, Malik P. A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction. Blood. 2009 Aug 6;114(6):1174-85.

Urbinati F, Arumugam P, Higashimoto T, Perumbeti A, Mitts K, Xia P, Malik P. Mechanism of reduction in titers from lentivirus vectors carrying large inserts in the 3'LTR. Mol Ther. 2009 Sep;17(9):1527-36.

Williams JP, Wu J, Johansson G, Rizvi TA, Miller SC, Geiger H, Malik P, Li W, Mukouyama YS, Cancelas JA, Ratner N. Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor that confers neurofibroma tumorigenic potential. Cell Stem Cell. 2008 Dec 4;3(6):658-69.

Tesfaye B. Mersha, PhD

is the principal investigator of a federally funded mentored research science award (K01). The goals of his research are to develop and evaluate an efficient approach to localize asthma liability genes in diverse African American populations in collaboration with members of the Department of Environmental Health at the University of Cincinnati, and to identify genes and regulatory networks that impact onset and severity of eczema.
Visit the Mersha Lab.

513-803-2766 tesfaye.mersha@cchmc.org

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Tesfaye B. Mersha, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-2766

Fax 513-636-1657

Email tesfaye.mersha@cchmc.org

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Visit Dr Mersha's external lab website.

Clinical

Allergy and allergy related disorders

Research

Quantitative and statistical genetics and genomics; genetic linkage, association and admixture analysis; expression analysis; network and pathway analysis; gene ontology and functional commonalities analysis

Visit Dr. Mersha's lab at Cincinnati Children's.

Biography

Tesfaye B. Mersha, PhD, is a quantitative geneticist. His background includes an early exposure to the many facets of biology and statistics and interested in cross-line disciplines to understand and solve complex genetic problems. During his post-doctoral fellowship program in statistical and human genetics, Dr. Mersha worked on statistical genetics methodologies and applied genetical data analysis to localize disease genes. Particularly, he focused on genetic analyses of metabolic and mental disorders using linkage, association and admixture mapping approach.

He developed genome-wide ancestry informative markers (AIMs) panel by mining databases including HapMap, Affymetrix and Illumina. The AIM markers are useful in ancestry inference, admixture mapping and structured association testing. He used over 4 million HapMap SNP data and developed approaches of chromosomal based finer population genetic structure characterization, localization of private SNPs and associated genes and pathways that could have pharmacogenomics implication.

In addition, Dr. Mersha is working on gene regulatory networks, gene ontology enrichment analysis and molecular profiling using various biologic and bioinformatic methodology for prioritizing asthma candidate genes. Dr. Mersha’s overall research interest and goal includes the use of population genomics, quantitative genetics, statistical genetics as well as proteomics and biological profiling and pathway methods to understand and dissect common complex diseases.

BS: Alemaya University, Ethiopia, 1992.

MS: Alemaya University, Ethiopia, 1996.

PhD: University of Göttingen, Germany, 2004.

Mersha TB. Mapping asthma-associated variants in admixed populations. Front Genet. 2015 Sep 29;6:292.

Ghosh D, Ding L, Sivaprasad U, Geh E, Biagini Myers J, Bernstein JA, Khurana Hershey GK, Mersha TB. Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways. PLoS One. 2015 Dec 30;10(12):e0144316.

Mersha TB, Abebe T. Self-reported race/ethnicity in the age of genomic research: its potential impact on understanding health disparities. Hum Genomics. 2015 Jan 7;9:1.

Ding L, Abebe T, Beyene J, Wilke RA, Goldberg A, Woo JG, Martin LJ, Rothenberg ME, Rao M, Hershey GK, Chakraborty R, Mersha TB. Rank-based genome-wide analysis reveals the association of Ryanodine receptor-2 gene variants with childhood asthma among human populations. Hum Genomics. 2013 Jul 5;7:16.

Amirisetty S, Hershey GK, Baye TM. AncestrySNPminer: A bioinformatics tool to retrieve and develop ancestry informative SNP panels. Genomics. 2012 Jul;100(1):57-63.

Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL, He H, Ericksen MB, Gupta J, Tsoras AM, Lindsley A, Rothenberg ME, Wills-Karp M, Eissa NT, Borish L, Hershey GK. Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children. PLoS One. 2011 Feb 28;6(2):e16522.

Baye TM, Abebe T, Wilke RA. Genotype-environment interaction and its translational implications. Personalized Medicine. 2011;8:59-70.

Baye TM, Wilke RA. Mapping genes that predict treatment outcome in admixed populations. Pharmacogenomics J. 2010 Dec;10(6):465-77.

Baye TM, Martin LJ, Khurana Hershey GK. Application of genetic/genomic approaches to allergic disorders. J Allergy Clin Immunol. 2010 Sep;126(3):425-36; quiz 437-8.

Baye TM, Wilke RA, Olivier M. Genomic and geographic distribution of private SNPs and pathways in human populations. Per Med. 2009 Nov 1;6(6):623-641.

Alexander G. Miethke, MD

is interested in susceptibility factors for neonatal liver injury, including biliary atresia. He focuses on the interaction between the maturing adaptive immune system and hepatic immune responses to infectious insults during the early neonatal period.

513-636-8948 alexander.miethke@cchmc.org

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Alexander G. Miethke, MD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-8948

Email alexander.miethke@cchmc.org

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Clinical

Pediatric liver disease including biliary atresia, inherited liver diseases, autoimmune hepatitis, and primary sclerosing cholangitis; gastrointestinal problems in children with bone marrow failure syndromes

Research

Immune mediated liver injury, specifically the role of regulatory T cells in biliary atresia and primary sclerosing cholangitis; genetic basis for intrahepatic cholestasis in children; acute liver failure in infants with mitochondrial disorders

Biography

Alexander G. Miethke, MD, joined the Division of Gastroenterology, Hepatology and Nutrition as a fellow in 2005, after completing his Pediatric Residency Training at Cincinnati Children's Hospital Medical Center. Following the completion of his fellowship, he pursued an additional year of training in pediatric transplant hepatology under the mentorship of Dr. William Balistreri and the physicians and surgeons of the Pediatric Liver Care Center.

In 2009, Dr. Miethke was appointed assistant professor of pediatrics in the Division of Gastroenterology, Hepatology and Nutrition and the Pediatric Liver Care Center at Cincinnati Children's within the UC Department of Pediatrics. His basic science research interests include the role of regulatory T cells in biliary atresia and other immune mediated liver diseases and the genetic basis of chronic cholestasis syndromes.

MD: Humboldt-University, Berlin, Germany, 2000.

Residency: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2002-2004.

Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2005-2007.

Advanced Fellowship: Pediatric Transplant Hepatology, University of Cincinnati and Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2009.

Certification: Pediatrics, 2005; Pediatric Gastroenterology, 2009; Pediatric Transplant Hepatology, 2010.

Evason K, Bove KE, Finegold MJ, Knisely AS, Rhee S, Rosenthal P, Miethke AG, Karpen SJ, Ferrell LD, Kim GE. Morphologic findings in progressive familial intrahepatic cholestasis 2 (PFIC2): correlation with genetic and immunohistochemical studies. Am J Surg Pathol. 2011;35:687-96.

Miethke AG, Saxena V, Shivakumar P, Sabla GE, Simmons J, Chougnet CA. Post-natal paucity of regulatory T cells and control of NK cell activation in experimental biliary atresia. J Hepatol. 2010 May;52(5):718-26.

Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, Bezerra JA. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. 2007 Jan;132(1):119-26.

Shivakumar P, Campbell KM, Sabla GE, Miethke A, Tiao G, McNeal MM, Ward RL, Bezerra JA. Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-gamma in experimental biliary atresia. J Clin Invest. 2004 Aug;114(3):322-9.

Ardythe L. Morrow, PhD Director, Center for Interdisciplinary Research in Human Milk and Lactation

513-636-7584 ardythe.morrow@cchmc.org

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Ardythe L. Morrow, PhD

Director, Center for Interdisciplinary Research in Human Milk and Lactation

Global Health Center

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7584

Fax 513-636-7509

Email ardythe.morrow@cchmc.org

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Clinical Interests

Human milk; child health and nutrition

Biography

Dr. Morrow received her MSc in nutrition from the University of the West Indies, Kingston, Jamaica (1980) and PhD in epidemiology from the University of Texas at Houston (1991). Since 1987 she has worked with colleagues in Mexico, Boston, and Houston on an NIH-funded program project on human milk immune protection against infectious disease.

She is currently professor of pediatrics at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine. She founded and directs the Center for Epidemiology and Biostatistics that has 35 faculty and staff and a multi-disciplinary Human Milk Research Program that includes clinical and basic science investigators in eight divisions.

She has published extensively on breastfeeding promotion and human milk protection against infectious diseases. Her primary focus is on protection by human milk glycans and protection against infectious disease, but she has expanded her research to understanding the relationship between breastfeeding and chronic diseases. She has been an ad hoc reviewer for NIH on breastfeeding research and a technical advisor for international breastfeeding policy and programs for Gates Foundation, UNICEF, and WHO, is on the editorial board of the Journal of Human Lactation and the journal of the Academy of Breastfeeding Medicine. She is an elected member of the American Pediatric Society. She has over 100 publications, and is the primary author of the WHO monograph, Community-based Strategies for Breastfeeding Promotion and Support in Developing Countries (2004).

She has served as chair of the Milk Club of the (American) Society for Pediatric Research for the past four years. In 1997, she received a Young Investigator award from ISRHML for her randomized trial of breastfeeding support (Lancet, 1999). She was co-organizer of the 2002 ISRHML international meeting in Mexico and is co-editor of the book "Protecting Infants through Human Milk: Advancing the Scientific Evidence."

BA: Rice University, Houston, TX.

MSc: University of the West Indies, Kingston, Jamaica.

PhD: The University of Texas School of Public Health, Houston, TX, 1991.

South AP, Wessel JJ, Sberna A, Patel M, Morrow AL. Hospital readmission among infants with gastroschisis. J Perinatol. 2011 Feb 10.

Morrow AL, Meinzen-Derr J, Huang P, Schibler KR, Cahill T, Keddache M, Kallapur SG, Newburg DS, Tabangin M, Warner BB, Jiang X. Fucosyltransferase 2 Non-Secretor and Low Secretor Status Predicts Severe Outcomes in Premature Infants. J Pediatr. 2011 May;158(5):745-51.

Farkas T, Cross RW, Hargitt E 3rd, Lerche NW, Morrow AL, Sestak K. Genetic diversity and histo-blood group antigen interactions of rhesus enteric caliciviruses. J Virol. 2010 Sep;84(17):8617-25.

Woo JG, Guerrero ML, Altaye M, Ruiz-Palacios GM, Martin LJ, Dubert-Ferrandon A, Newburg DS, Morrow AL. Human milk adiponectin is associated with infant growth in two independent cohorts. Breastfeed Med. 2009 Jun;4(2):101-9.

Huang P, Morrow AL, Jiang X. The carbohydrate moiety and high molecular weight carrier of histo-blood group antigens are both required for norovirus-receptor recognition. Glycoconj J. 2009 Nov;26(8):1085-96.

Meinzen-Derr J, Morrow AL, Hornung RW, Donovan EF, Dietrich KN, Succop PA. Epidemiology of necrotizing enterocolitis temporal clustering in two neonatology practices. J Pediatr. 2009 May;154(5):656-61.

Geraghty SR, Khoury JC, Morrow AL, Lanphear BP. Reporting individual test results of environmental chemicals in breast milk: potential for premature weaning. Breastfeed Med. 2008 Dec;3(4):207-13.

Olsen IE, Lawson ML, Meinzen-Derr J, Sapsford AL, Schibler KR, Donovan EF, Morrow AL. Use of a body proportionality index for growth assessment of preterm infants. J Pediatr. 2009 Apr;154(4):486-91.

Meinzen-Derr J, Poindexter B, Wrage L, Morrow AL, Stoll B, Donovan EF. Role of human milk in extremely low birth weight infants' risk of necrotizing enterocolitis or death. J Perinatol. 2009 Jan;29(1):57-62.

Woo JG, Dolan LM, Morrow AL, Geraghty SR, Goodman E. Breastfeeding helps explain racial and socioeconomic status disparities in adolescent adiposity. Pediatrics. 2008 Mar;121(3):e458-65.

Takahisa Nakamura, PhD

Research goal is to address questions concerning why and how inflammatory responses are initiated, coordinated, and thus involved in the development of obesity-induced metabolic diseases.

513-636-4744 takahisa.nakamura@cchmc.org

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Takahisa Nakamura, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-4744

Email takahisa.nakamura@cchmc.org

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RNA-related inflammation in obesity and metabolic diseases

Biography

Dr. Nakamura received his PhD from the University of Tokyo in 2003. He completed postdoctoral training in the laboratory of Dr. Gökhan S. Hotamisligil at Harvard School of Public Health in 2013, followed by his faculty appointment at Cincinnati Children's Hospital Medical Center within the UC Department of Pediatrics in 2013.

PhD: University of Tokyo, 2003.

Postdoctoral Fellow: University of Tokyo, 2003-2006.

Research Fellow: Harvard University, 2006-2010.

Research Associate: Harvard University, 2010-2013.

Nakamura T, Arduini A, Baccaro B, Furuhashi M, Hotamisligil GS. Small molecule inhibitors of PKR improve glucose homeostasis in obese, diabetic mice. Diabetes. 2014 Feb;63(2):526-34.

Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundbäck P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012 Aug 20;488(7413):670-4.

Morita M. Oike Y, Nagashima T, Kadomatsu T, Tabata M, Suzuki T, Nakamura T, Yoshida N, Okada M, Yamamoto T. Obesity resistance and increased hepatic expression of catabolism-related mRNAs in Cnot3(+/-) mice. EMBO J. 2011 Sep 6;30(22):4678-4691.

Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS. Double-stranded RNA-dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell. 2010 Feb 5;140(3):338-48.

Yoneda M, Suzuki T, Nakamura T, Ajima R, Yoshida Y, Kakuta S, Sudo K, Iwakura Y, Shibutani M, Mitsumori K, Yokota J, Yamamoto T. Deficiency of antiproliferative family protein Ana correlates with development of lung adenocarcinoma. Cancer Sci. 2009 Feb;100(2):224-232.

Ajima R, Akiyama T, Usui M, Yoneda M, Yoshida Y, Nakamura T, Minowa O, Noda M, Tanaka S, Noda T, Yamamoto T. Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation. FEBS Lett. 2008 Apr 16;582(9):1313-8.

Morita M, Suzuki T, Nakamura T, Yokoyama K, Miyasaka T, Yamamoto T. Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA level and impairs cell growth. Mol Cell Biol. 2007 Jul;27(13):4980-90.

Nakamura T, Yao R, Ogawa T, Suzuki T, Ito C, Tsunekawa N, Inoue K, Ajima R, Miyasaka T, Yoshida Y, Ogura A, Toshimori K, Noce T, Yamamoto T, Noda T. Oligoasthenoteratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta. Nat Genet. 2004 May;36(5):528-33.

Kimura H*, Nakamura T*, Ogawa T, Tanaka S, Shiota K. Transcription of mouse DNA methyltransferase 1 (Dnmt1) is regulated by both E2F-Rb-HDAC-dependent and -independent pathways. Nucleic Acids Res. 2003 Jun 15;31(12):3101-13. *These authors contributed equally to this work.

Yoshida Y*, Nakamura T*, Komoda M, Satoh H, Suzuki T, Tsuzuku JK, Miyasaka T, Yoshida EH, Umemori H, Kunisaki RK, Tani K, Ishii S, Mori S, Suganuma M, Noda T, Yamamoto T. Mice lacking a transcriptional corepressor Tob are predisposed to cancer. Genes Dev. 2003 May 15;17(10):1201-6. *These authors contributed equally to this work.

Grants

Analysis of pathogenic double-stranded RNA in chronic inflammatory diseases. Principal Investigator. Japan Science and Technology Agency, PRESTO. Feb 2013–Mar 2016.

Joseph E. Qualls, PhD

examines the cellular and molecular facets of macrophage biology during health and disease. This white blood cell has an unprecedented role in regulating inflammation, pathogen elimination and maintaining tissue homeostasis. Specifically, Dr. Qualls’ laboratory focuses on amino acid utilization by macrophages, and how this affects the outcome of infection and inflammatory disease.

513-636-9102 joseph.qualls@cchmc.org

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Joseph E. Qualls, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-636-9102

Email joseph.qualls@cchmc.org

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Immunology; innate immunity; macrophage biology; amino acid metabolism; intracellular pathogenesis

Biography

Dr. Qualls completed his undergraduate work in 2002, receiving his BA summa cum laude in biology from Thomas More College in Crestview Hills, KY. He then joined the laboratory of Don Cohen, PhD, in the Department of Microbiology, Immunology, and Molecular Genetics at the University of Kentucky, where he studied the role of macrophages and dendritic cells during the development of inflammatory bowel disease. After defending his thesis and receiving his PhD in 2007, Dr. Qualls began his postdoctoral training with Peter Murray, PhD, in the Department of Infectious Diseases and Immunology at St. Jude Children’s Research Hospital in Memphis, TN, where his research helped to define the functional plasticity of macrophages in response to infection and cancer. During his postdoctoral training, Dr. Qualls received a Ruth L. Kirschstein National Research Service Award and actively participated as vice chair of mentoring activities within the Postdoctoral Association Council and as a member of the Education Programs Committee.

Dr. Qualls’ long-term goals are to understand the interplay between nutrition, metabolism, and immune regulation during anti-pathogen defense. He has focused on how macrophages use the amino acid, L-arginine, to combat intracellular pathogens. As a starting point to appreciate broader principles of immunity and metabolism he established a map of L-arginine metabolism at the transcriptomic and metabolomic levels. His laboratory now uses this map to dissect how L-arginine generates anti-microbial effectors, how this pathway is regulated, and how microbes can hijack the pathway. His current research has two complementary tracks that retain initial focus on L-arginine metabolism in macrophages, but will eventually broaden into larger issues concerning metabolism in immunity.

Current research: Many groups have shown that T cell function is inhibited via byproducts of L-arginine metabolism or when extracellular L-arginine becomes limiting. In one project, the laboratory is focused on characterizing the in vivo function of L-arginine utilization by macrophages during mycobacterial infection, and how this affects anti-pathogen T cell function. In parallel, the laboratory is addressing the provocative role of L-arginine biosynthesis from L-citrulline during intracellular infection, and how this mechanism is regulated at the cellular level. While greatly unexplored, this pathway of amino acid recycling is vital as mice deficient in L-arginine biosynthesis, compared to normal mice, lack efficient control of both M. bovis BCG and M. tuberculosis infection.

BA: Thomas More College, Crestview Hills, KY, 2002.

PhD: University of Kentucky, Lexington, KY, 2007.

Postdoctoral Fellowship: St. Jude Children’s Research Hospital, Memphis, TN, 2012.

Rapovy SM, Zhao J, Bricker RL, Schmidt SM, Setchell KDR, Qualls JE. Differential requirements for L-citrulline and L-arginine during anti-mycobacterial macrophage activity. Journal of Immunology. 2015 Oct 1;195(7):3293-300.

Kratochvill F, Neale G, Haverkamp JM, Van de Velde L, Smith AM, Kawauchi D, McEvoy J, Roussel MF, Dyer MA, Qualls JE, Murray PJ. TNF counterbalances the emergence of M2 tumor macrophages. Cell Reports. 2015 Sep 22;12(11):1902-14.

Kratochvill F, Gratz N, Qualls JE, Van De Velde LA, Chi H, Kovarik P, Murray PJ. Tristetraprolin Limits Inflammatory Cytokine Production in Tumor-Associated Macrophages in an mRNA Decay-Independent Manner. Cancer Research. 2015 Aug 1;75(15):3054-64.

Haverkamp JM, Smith AM, Weinlich R, Dillon CP, Qualls JE, Neale G, Koss B, Kim Y, Bronte V, Herold MJ, Green DR, Opferman JT, Murray PJ. Myeloid-derived suppressor activity is mediated by monocytic lineages maintained by continuous inhibition of extrinsic and intrinsic death pathways. Immunity. 2014 Dec 18;41(6):947-59.

Duque-Correa MA, Kuhl A, Rodriquez PC, Zedler U, Schommer-Leitner S, Rao M, Weiner J, Hurwitz R, Qualls JE, Kosmiadi GA, Murray PJ, Kaufmann SHE, Reece ST. Macrophage arginase-1 controls bacterial growth and pathology in hypoxic tuberculosis granulomas. Proceedings of the National Academy of Sciences – USA. 2014 Sep 23;111(38):E4024-32.

Barron L, Smith AM, El Kasmi KC, Qualls JE, Huang X, Cheever A, Borthwick LA, Wilson MS, Murray PJ, Wynn TA. Role of arginase 1 from myeloid cells in Th2-dominated lung inflammation. PLOS One. 2013 Apr 24;8(4):e61961.

Qualls JE, Subramanian C, Smith AM, Balouzian L, DeFreitas AA, Shirey KA, Reutterer B, Kernbauer E, Stockinger S, Decker T, Miyairi I, Vogel SN, Rock CO, Murray PJ. Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1. Cell Host & Microbe. 2012 Sep 13;12(3):313-23.

Smith AM, Qualls JE, O’Brien K, Balouzian L, Johnson PF, Schultz-Cherry S, Smale ST, Murray PJ. A Distal Enhancer in Il12b is the Target of Transcriptional Repression by the Stat3 Pathway and Requires the B-Zip Protein NFIL-3. Journal of Biological Chemistry. 2011 Jul 1; 286(26):23582-90.

Qualls JE, Neale G, Smith AM, Koo MS, DeFreitas AA, Zhang H, Kaplan G, Watowich SS, Murray PJ. Arginine usage in mycobacteria-infected macrophages depends on autocrine-paracrine cytokine signaling. Science Signaling. 2010 Aug 17;3(135):ra62.

El Kasmi KC, Qualls JE (co-primary author), Pesce JT, Smith AM, Thompson RW, Henao-Tamayo M, Basaraba RJ, König T, Schleicher U, Koo M, Kaplan G, Fitzgerald KA, Tuomanen EI, Orne IM, Kanneganti T, Bogdan C, Wynn TA, Murray PJ. TLR-induced Arginase 1 thwarts effective immunity against intracellular pathogens. Nature Immunology. 2008 Dec;9(12):1399-406.

Grants

L-citrulline and host defenses to mycobacteria. Principle Investigator. American Heart Association. Jan 2015–Dec 2017.

Nancy Ratner, PhD Beatrice C. Lampkin Chair, Cancer Biology

is working to define the interactions between glial cells and axons during nervous system development and how those interactions go awry in disease. Her goal is to develop novel therapies for patients with nervous system diseases.

Visit the Ratner Lab.

513-636-9469 nancy.ratner@cchmc.org

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Nancy Ratner, PhD

Beatrice C. Lampkin Chair, Cancer Biology

Program Leader, Cancer and Biology and Neural Tumors Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-9469

Fax 513-636-3549

Email nancy.ratner@cchmc.org

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Clinical/Translational

Preclinical testing in neurofibromatosis tumors

Research

Genetic mutations in tumor suppressor genes; development of the nervous system; peripheral nerve tumor formation

Visit the Ratner Lab.

Biography

Nancy Ratner, PhD, is interested in understanding mechanisms of peripheral nerve tumor (neurofibroma) formation in neurofibromatosis type 1 (NF1), a common inherited disorder in which children are predisposed to cancer of the nervous system, to learning problems, bone disorders, and other cancers. She identified EGFR and MEK as potential therapeutic targets in NF1 peripheral nerve tumorigenesis, and has developed cell culture and mouse models of NF1 nerve tumorigenesis. Her laboratory has also used analysis of gene expression to identify critical genes in neurofibroma and their malignant derivatives, MPNST.

Dr. Ratner received her bachelor's from Brown University, her doctorate from Indiana University, and was a postdoctoral fellow at Washington University in St. Louis. She was a member of the faculty at the University of Cincinnati from 1987 to 2004. Dr. Ratner is currently a professor in the Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, and the program leader for Cancer Biology and Neural Tumors Program in the Cancer and Blood Diseases Institute where she holds the Beatrice C. Lampkin Endowed chair in cancer biology and serves as PI of the NINDS P50 “Cincinnati Center in NF Research.”

Dr. Ratner is an active member of the International Consortium on the Molecular Biology of NF1, NF2, and Schwannomatosis and was a member of the advisory board for the National Neurofibromatosis Foundation (now Children’s Tumor Foundation) from 1989 to 2007. She chaired the Department of Defense Neurofibromatosis Research Program Integration Panel in 2008, and currently serves as a member of the James McDonnell Brain Tumor Research Advisory Board. She received the von Recklinghausen Award from the Children’s Tumor Foundation in 2010 and the Jacob K. Javits Neuroscience Investigator Award (NIH-NINDS MERIT Award) in 2014.

PhD: Indiana University, 1982.

BA: Brown University, 1975.

Fellowship: Washington University St. Louis, 1982-1987.

Mayes DA, Rizvi TA, Titus-Mitchell HA, Oberst R, Ciraolo GM, Vorhees CV, Robinson AP, Miller SD, Stemmer-Rachamimov AO, Ratner N. Nf1 loss and Ras activation in Oligodendrocytes induce NOS-driven Defects in Myelin and Vasculature. Cell Reports. 2013 Sep 26;4(6):1197-212.

Rahrmann EP, Watson AL, Keng VW, Choi K, Moriarity B, Beckmann DA, Wolf N, Sarver A, Collins MH, Moertel CL, Wallace MR, Gel B, Serra S, Ratner N, Largaespada DA. Forward genetic screen for malignant peripheral nerve sheath tumor formation identifies novel genes and genetic pathways driving tumorigenesis. Nature Genetics. 2013;45(7):756-66.

Watson AL, Rahrmann EP, Moriarity B, Choi K, Conboy C, Greeley A, Halfond A, Anderson L, Wahl B, Keng VW, Rizzardi A, Forser C, Collins MH, Sarver A, Wallace M, Schmechel S, Ratner N, Largaespada DA. Canonical Wnt/β-catenin Signaling Drives Human Schwann Cell Transformation, Progression, and Tumor Maintenance. Cancer Discov. 2013 Jun;3(6):674-689.

Prada CE, Jousma E, Rizvi TA, Wu J, Dunn RS, Mayes DA, Cancelas JA, Dombi E, West BL, Bollag G, Ratner N. Neurofibroma associated macrophages play roles in tumor growth and response to pharmacological inhibition. Acta Neurpathol. 2013;125(1):159-68.

Jessen WJ, Miller SJ, Jousma E, Rizvi TA, Eaves D, Wu J, Widemann B, Kim M-O, Dombi E, Dudley AH, Niwa-Kawakita M, Page GP, Giovannini M, Aronow BJ, Cripe TP, Ratner N. MEK Inhibition Exhibits Efficacy in Human and Mouse Neurofibromatosis Tumors Despite Transcriptional Feedback onto ERK. J Clin. Invest. 2013 Jan 2;123(1):340-7.

Patel AV, Eaves D, Jessen WJ, Rizvi TA, Ecsedy JA, Qian MG, Aronow BJ, Perentesis JP, Serra E, Cripe TP, Miller SJ, Ratner N. Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target. Clin Canc Res. 2012 Sep 15;18(18):5020-30.

Hennigan RF, Moon CO, Parysek LM, Monk KR, Morfini G, Berth S, Brady ST, Ratner N. Merlin Modulates Microtubule-Based Vesicle Trafficking via Rac, MLK and p38SAPK. Oncogene. 2012;29(3):368-79.

Mayes DA, Rizvi TA, Cancelas JA, Kolasinski NT, Ciraolo GM, Stemmer-Rachamimov AO, Ratner N. Perinatal or Adult Nf1 Inactivation Using Tamoxifen-Inducible PlpCre Each Cause Neurofibroma Formation. Cancer Res. 2011 Jul 1;71(13):4675-85.

Hummel TR, Jessen WJ, Miller SC, Kluwe L, Mautner VF, Wallace MR, Lázaro C, Page G, Worley P, Aronow BJ, Schorry E, Ratner N. Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin Cancer Res. 2010;16 5048-57.

Miller SJ, Jessen WJ, Mehta T, Hardiman A, Sites E, Kaiser S, Jegga A, Li H, Upadhyaya M, Giovannini M, Muir D, Wallace MR, Lopez E, Serra E, Lazaro C, Stemmer-Rachamimov A, Page G, Aronow BJ, Ratner N. Integrative genomic analyses of neurofibromatosis tumors identify SOX9 as biomarker and survival gene. EMBO Mol Medicine. 2009 1(4): 236-48.

Grants

Mitogenic Activities in Neurofibromatosis. Principle Investigator. Sept 2011-2016. NIH-R01 NS 28840-20.

Preclinical Testing: GEM-Neurofibroma. Principal Investigator. Children's Tumor Foundation. Aug 2013-Jul 2016.

Identification of Neurofibroma Growth and Drug Resistance Pathways. Principal Investigator. Neurofibromatosis Therapeutic Acceleration Program (NTAP). Apr 2014-Mar 2016.

Ras Proteins in Nerve Tumorigenesis. Principal Investigator. Apr 2014-Mar 2019. 1R01 NS083580-01A1.

Novel Combinatorial Therapies for Malignant Peripheral Nerve Sheath Tumors. Co-Principal Investigator. Jul 2014-Jun 2016. 1R21NS084885-01A1.

Disordered Wnt/b-catenin signaling in MPNST Development and Maintenance. Co-Principal Investigator. Oct 2014-Sep 2019. 1R01NS086219-01A1.

Can targeted therapy prevent neurofibroma growth in mice? Principal Investigator. Neurofibromatosis Therapeutic Acceleration Program (NTAP). Sep 2014-Aug 2016.

William Ridgway, MD

research investigates autoimmunity, immunogenetics, T cells, autoimmune (type I) diabetes, autoimmune liver disease (primary biliary cirrhosis), and relapsing polychondritis. The goal of the Ridgway Lab is to determine the immunogenetic mechanisms of autoimmune biliary disease, type one diabetes, and relapsing polychondritis arising in nonobese diabetic (NOD) and NOD congenic mice.

Visit the Ridgway Lab.

513-558-4701 william.ridgway@uc.edu

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William Ridgway, MD

Academic Affiliations

Professor, UC Department of Internal Medicine

Phone 513-558-4701

Email william.ridgway@uc.edu

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Autoimmunity; immunogenetics; T cells; T regulatory cells; type 1 diabetes; autoimmune biliary disease

MD: University of Rochester, Rochester, NY.

Fellowship: Stanford University Medical Center, Stanford, CA.

Visit the Rothenberg Lab website.

Yang GX, Wu Y, Tsukamoto H, Leung PS, Lian ZX, Rainbow DB, Hunter KM, Morris GA, Lyons PA, Peterson LB, Wicker LS, Gershwin ME, Ridgway WM. CD8 T cells mediate direct biliary ductule damage in nonobese diabetic autoimmune biliary disease. J Immunol. 2011 Jan 15;186(2):1259-67.

Ridgway WM, Peterson LB, Todd JA, Rainbow DB, Healy B, Burren OS, Wicker LS. Gene-gene interactions in the NOD mouse model of type 1 diabetes. Adv Immunol. 2008;100:151-75.

Irie J, Reck B, Wu Y, Wicker LS, Howlett S, Rainbow D, Feingold E, Ridgway WM. Genome-wide microarray expression analysis of CD4+ T Cells from nonobese diabetic congenic mice identifies Cd55 (Daf1) and Acadl as candidate genes for type 1 diabetes. J Immunol. 2008 Jan 15;180(2):1071-9.

Irie J, Wu Y, Sass DA, Ridgway WM. Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region. Immunogenetics. 2006 Feb;58(1):9-14.

Koarada S, Wu Y, Fertig N, Sass DA, Nalesnik M, Todd JA, Lyons PA, Fenyk-Melody J, Rainbow DB, Wicker LS, Peterson LB, Ridgway WM. Genetic control of autoimmunity: protection from diabetes, but spontaneous autoimmune biliary disease in a nonobese diabetic congenic strain. J Immunol. 2004 Aug 15;173(4):2315-23.

Koarada S, Wu Y, Olshansky G, Ridgway WM. Increased nonobese diabetic Th1:Th2 (IFN-gamma:IL-4) ratio is CD4+ T cell intrinsic and independent of APC genetic background. J Immunol. 2002 Dec 1;169(11):6580-7.

Koarada S, Wu Y, Ridgway WM. Increased entry into the IFN-gamma effector pathway by CD4+ T cells selected by I-Ag7 on a nonobese diabetic versus C57BL/6 genetic background. J Immunol. 2001 Aug 1;167(3):1693-702.

Fassò M, Anandasabapathy N, Crawford F, Kappler J, Fathman CG, Ridgway WM. T cell receptor (TCR)-mediated repertoire selection and loss of TCR vbeta diversity during the initiation of a CD4(+) T cell response in vivo. J Exp Med. 2000 Dec 18;192(12):1719-30.

Ridgway WM, Fassò M, Fathman CG. A new look at MHC and autoimmune disease. Science. 1999 Apr 30;284(5415):749, 751.

Ridgway WM, Ito H, Fassò M, Yu C, Fathman CG. Analysis of the role of variation of major histocompatibility complex class II expression on nonobese diabetic (NOD) peripheral T cell response. J Exp Med. 1998 Dec 21;188(12):2267-75.

Marc E. Rothenberg, MD, PhD Director, Division of Allergy and Immunology

is focused on elucidating mechanisms of allergic responses, especially in mucosal tissues such as the lung and the gastrointestinal tract, in order to identify novel pharmaceutical targets for treatment of patients with eosinophilic diseases including eosinophilic gastrointestinal disorders, hypereosinophilic syndromes and asthma and food allergies. Lab has identified and characterized several critical pathways that regulate allergic responses.

513-803-0257 marc.rothenberg@cchmc.org

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Marc E. Rothenberg, MD, PhD

Director, Division of Allergy and Immunology

Director, Cincinnati Center for Eosinophilic Disorders

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-0257

Fax 513-636-3310

Email marc.rothenberg@cchmc.org

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Visit the Rothenberg Lab.

Clinical

Eosinophilia; eosinophilic disorders; asthma; allergy; food allergy

Research

Eosinophils; chemokines

Biography

Visit the Rothenberg Lab website.

Dr. Rothenberg is director of the Division of Allergy and Immunology at Cincinnati Children's Hospital Medical Center and tenured professor of pediatrics at Cincinnati Children’s within the University of Cincinnati College of Medicine. He graduated summa cum laude with highest honors in chemistry and biochemistry from Brandeis University. He then completed the MD/PhD program at Harvard Medical School under Dr. Frank Austen, conducting studies on eosinophil hematopoiesis, as he developed the first culture system for human eosinophils. After completing residency at Children’s Hospital, Boston, Dr. Rothenberg did a fellowship in allergy/immunology and hematology at Children’s Hospital. Dr. Rothenberg did post-doctorate training with Dr. Philip Leder, Harvard Medical School, where he cloned the eotaxin chemokine. After being faculty at Harvard Medical School for one year, he came to the University of Cincinnati and Cincinnati Children's, where he has helped build a top program in research, and his division is a leader in allergy and immunology.

His research is focused on molecular analysis of allergic inflammation, primarily on the molecular pathogenesis of eosinophilic esophagitis. His laboratory takes a multi-disciplinary approach including the development of preclinical murine models: genetics, genomics, molecular immunology, and biochemistry. Dr. Rothenberg’s awards include the 2007 E Mead Johnson Award from the Society of Pediatric Research, 2010 National Institutes of Health MERIT Award, and being elected an American Association for the Advancement of Science fellow. He is a member of the American Society for Clinical Investigation, American Academy of Pediatrics, and Society for Pediatric Radiology. His publications number over 300. He has served on review panels for journals/grant agencies including National Institutes of Health (NIH), Burroughs Trust, and Medical Research Council of the United Kingdom. He served for four years on the Advisory Council of National Institute of Allergy and Infectious Disease. He has been associate editor of the Journal of Allergy and Clinical Immunology since 2004. His research has been supported by sources including the NIH, Human Frontier Science Program Organization, Burroughs Wellcome Fund, Dana Foundation, and Department of Defense.

MD, PhD: Harvard Medical School, Cambridge, MA, 1990.

Residency: Pediatrics, Children's Hospital, Boston, MA, 1991-1992.

Fellowship: Immunology / Allergy, Children's Hospital, Boston, MA, 1992-1994; Hematology / Oncology, Children's Hospital and Dana Farber Cancer Institute, Boston, MA, 1992-1995.

Certification: National Board of Medical Examiners, 1991; Board of Registration in Medicine, MA, 1992; American Board of Pediatrics, 1995, 2001, 2008; Ohio State Medical Board, 1997; American Board of Allergy and Immunology, 1997, 2006.

Butz BK, Wen T, Gleich GJ, Furuta GT, Spergel J, King E, Kramer RE, Collins MH, Stucke E, Mangeot C, Jackson WD, O'Gorman M, Abonia JP, Pentiuk S, Putnam PE, Rothenberg ME. Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis. Gastroenterology. 2014 Aug;147(2):324:33.e5.

Sherrill JD, Kc K, Wu D, Djukic Z, Caldwell JM, Stucke EM, Kemme KA, Costello MS, Mingler MK, Blanchard C, Collins MH, Abonia JP, Putnam PE, Dellon ES, Orlando RC, Hogan SP, Rothenberg ME. Desmoglein-1 regulates esophageal epithelial barrier function and immune responses in eosinophilic esophagitis. Mucosal Immunol. 2014 May;7(3):718-29.

Wen T, Stucke EM, Grotjan TM, Kemme KA, Abonia JP, Putnam PE, Franciosi JP, Garza JM, Kaul A, King EC, Collins MH, Kushner JP, Rothenberg ME. Molecular diagnosis of eosinophilic esophagitis by gene expression profiling. Gastroenterology. 2013 Dec;145(6):1289-99.

Wen T, Besse JA, Mingler MK, Fulkerson PC, Rothenberg ME. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo. Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6067-72.

Lu TX, Sherrill JD, Wen T, Plassard AJ, Besse JA, Abonia JP, Franciosi JP, Putnam PE, Eby M, Martin LJ, Aronow BJ, Rothenberg ME. MicroRNA signature in patients with eosinophilic esophagitis, reversibility with glucocorticoids, and assessment as disease biomarkers. J Allergy Clin Immunol. 2012 Apr;129(4):1064-75.e9.

Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, Cianferoni A, Gober L, Kim C, Glessner J, Frackelton E, Thomas K, Blanchard C, Liacouras C, Verma R, Aceves S, Collins MH, Brown-Whitehorn T, Putnam PE, Franciosi JP, Chiavacci RM, Grant SF, Abonia JP, Sleiman PM, Hakonarson H. Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet. 2010 Apr;42(4):289-91.

Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ; Mepolizumab HEC Study Group. Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med. 2008 Mar 20;358(12):1215-28.

Blanchard C, Wang N, Stringer KF, Mishra A, Fulkerson PC, Abonia JP, Jameson SC, Kirby C, Konikoff MR, Collins MH, Cohen MB, Akers R, Hogan SP, Assa'ad AH, Putnam PE, Aronow BJ, Rothenberg ME. Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis. J Clin Invest. 2006 Feb;116(2):536-47.

Hogan SP, Mishra A, Brandt EB, Royalty MP, Pope SM, Zimmermann N, Foster PS, Rothenberg ME. A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation. Nat Immunol. 2001 Apr;2(4):353-60.

Mishra A, Hogan SP, Brandt EB, Rothenberg ME. An etiological role for aeroallergens and eosinophils in experimental esophagitis. J Clin Invest. 2001 Jan;107(1):83-90.

Grants

NICHHD Pediatric Center for Gene Expression and Developmental Sciences. Training Director. National Institutes of Health. Dec 2011–Nov 2016. K12 HD028827.

Epithelial Genes in Allergic Inflammation. Co-Investigator. National Institutes of Health. Sep 2011–Aug 2016. U19 AI070235.

Eosinophil:M2 Macrophage:CCL11 Axis in Experimental Colitis and Pediatric Corticosteroid Resistant Ulcerative Colitis. Co-Investigator. National Institutes of Health. Apr 2012–Mar 2016. R01 DK090119-01A1.

The Expression and Function of Paired Immunoglobulin-like Receptor B in Eosinophils. Co-Principal Investigator. U.S. - Israel Binational Science Foundation. Oct 2012–Sep 2016. #201144.

Nancy M. Sawtell, PhD

leads studies of herpes simplex virus and has identified VP16, the first gene essential for triggering the virus’s emergence from its latent state in the human nervous system. Reactivation of the virus in the brains of older mice carrying the human APOE 4 gene to leads to lesions that resemble Alzheimer’s.
Visit the Sawtell Lab.

513-636-7880 nancy.sawtell@cchmc.org

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Nancy M. Sawtell, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7880

Fax 513-636-7655

Email nancy.sawtell@cchmc.org

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Clinical

Molecular mechanisms of herpes virus latency and reactivation; viral persistence; pathogenesis; animal models of disease

Research

Visit the Sawtell Lab.

BA: Chemistry, Case Western Reserve University, 1975.

PhD: Pathology and Immunology, University of Cincinnati Medical College, Cincinnati, OH, 1986.

Farley N, Bernstein DI, Bravo FJ, Earwood J, Sawtell N, Cardin RD. Recurrent vaginal shedding of herpes simplex type 2 virus in the mouse and effects of antiviral therapy. Antiviral Res. 2010 May;86(2):188-95.

Thompson RL, Preston CM, Sawtell NM. De novo synthesis of VP16 coordinates the exit from HSV latency in vivo. PLoS Pathog. 2009 Mar;5(3):e1000352.

Currier MA, Gillespie RA, Sawtell NM, Mahller YY, Stroup G, Collins MH, Kambara H, Chiocca EA, Cripe TP. Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide. Mol Ther. 2008 May;16(5):879-85.

Thompson RL, Sawtell NM. Evidence that the herpes simplex virus type 1 ICP0 protein does not initiate reactivation from latency in vivo. J Virol. 2006 Nov;80(22):10919-30.

Sawtell NM, Thompson RL, Haas RL. Herpes simplex virus DNA synthesis is not a decisive regulatory event in the initiation of lytic viral protein expression in neurons in vivo during primary infection or reactivation from latency. J Virol. 2006 Jan;80(1):38-50.

Sawtell NM. Detection and quantification of the rare latently infected cell undergoing herpes simplex virus transcriptional activation in the nervous system in vivo. Methods Mol Biol. 2005;292:57-72.

Sawtell NM, Thompson RL. Comparison of herpes simplex virus reactivation in ganglia in vivo and in explants demonstrates quantitative and qualitative differences. J Virol. 2004 Jul;78(14):7784-94.

Thompson RL, Shieh MT, Sawtell NM. Analysis of herpes simplex virus ICP0 promoter function in sensory neurons during acute infection, establishment of latency, and reactivation in vivo. J Virol. 2003 Nov;77(22):12319-30.

Sawtell NM. Quantitative analysis of herpes simplex virus reactivation in vivo demonstrates that reactivation in the nervous system is not inhibited at early times postinoculation. J Virol. 2003 Apr;77(7):4127-38.

Sawtell NM, Thompson RL, Stanberry LR, Bernstein DI. Early intervention with high-dose acyclovir treatment during primary herpes simplex virus infection reduces latency and subsequent reactivation in the nervous system in vivo. J Infect Dis. 2001 Oct 15;184(8):964-71.

Harinder Singh, PhD Director, Division of Immunobiology

513-636-7641 harinder.singh@cchmc.org

Daniel T. Starczynowski, PhD

is a cancer biologist who has a basic research programs with a translational emphasis in myeloid hematological malignancies. His lab’s major effort is studying the molecular and cellular basis of myelodysplastic syndromes, bone marrow failure syndromes and acute leukemia. The goal is to identify candidate genes and understand their contribution to myeloid malignancies.
Visit the Starczynowski Lab.

513-803-5317 daniel.starczynowski@cchmc.org

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Daniel T. Starczynowski, PhD

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-803-5317

Email daniel.starczynowski@cchmc.org

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Visit the Starczynowski Lab.

Biography

Daniel T. Starczynowski, PhD, received his PhD in molecular biology from Boston University. He studied the NF-kB family of transcription factors and their role in B-cell lymphomas. During his postdoctoral fellowship at the BC Cancer Research Center, Dr. Starczynowski identified and characterized novel candidate genes in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

Following his postdoctoral training, Dr. Starczynowski joined the faculty at Cincinnati Children’s Hospital Medical Center and at the University of Cincinnati as an assistant professor. Dr. Starczynowski’s laboratory is continuing to investigate the molecular and cellular basis of MDS. The current objective of his research program is to understand the contribution of MDS-associated miRNAs and their targeted genes to the pathogenesis of MDS and progression to AML. He hopes that understanding some of the molecular causes of MDS will enhance our insight into the biology of MDS, and provide novel targeted therapies.

BS: Fairleigh Dickinson University, Teaneck, NJ, 2000.

PhD: Boston University, Boston, MA, 2006.

Postdoctoral Fellow: University of British Columbia/BC Cancer Research Centre, Vancouver, Canada, 2010.

Varney ME, Niederkorn M, Konno H, Matsumura T, Gohda J, Yoshida N, Akiyama T, Christie S, Fang J, Miller D, Jerez A, Karsan A, Maciejewski JP, Meetei RA, Inoue J, Starczynowski DT. Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. J Exp Med. 2015 Oct 19;212(11):1967-85.

Varney ME, Melgar K, Niederkorn M, Smith MA, Barreyro L, Starczynowski DT. Deconstructing innate immune signaling in myelodysplastic syndromes. Exp Hematol. 2015 Aug;43(8):587-98.

Fang J, Barker B, Bolanos L, Liu X, Jerez A, Makishima H, Christie S, Chen X, Rao DS, Grimes HL, Komurov K, Weirauch MT, Cancelas JA, Maciejewski JP, Starczynowski DT. Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network. Cell Rep. 2014 Sep 11;8(5):1328-38.

Zhao JL, Starczynowski DT. Role of microRNA-146a in normal and malignant hematopoietic stem cell function. Front Genet. 2014 Jul 9;5:219.

Rhyasen GW, Wunderlich M, Tohyama K, Garcia-Manero G, Mulloy JC, Starczynowski DT. An MDS xenograft model utilizing a patient-derived cell line. Leukemia. 2014 May;28(5):1142-5.

Rhyasen GW, Bolanos L, Fang J, Jerez A, Wunderlich M, Rigolino C, Mathews L, Ferrer M, Southall N, Guha R, Keller J, Thomas C, Beverly LJ, Cortelezzi A, Oliva EN, Cuzzola M, Maciejewski JP, Mulloy JC, Starczynowski DT. Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome. Cancer Cell. 2013 Jul 8;24(1):90-104.

Fang J, Rhyasen G, Bolanos L, Rasch C, Varney M, Wunderlich M, Goyama S, Jansen G, Cloos J, Rigolino C, Cortelezzi A, Mulloy JC, Oliva EN, Cuzzola M, Starczynowski DT. Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1. Blood. 2012 Jul 26;120(4):858-67.

Starczynowski DT, Lockwood WW, Deléhouzée S, Chari R, Wegrzyn J, Fuller M, Tsao MS, Lam S, Gazdar AF, Lam WL, Karsan A. TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. J Clin Invest. 2011 Oct;121(10):4095-105.

Starczynowski DT, Morin R, McPherson A, Lam J, Chari R, Wegrzyn J, Kuchenbauer F, Hirst M, Tohyama K, Humphries RK, Lam WL, Marra M, Karsan A. Genome-wide identification of human microRNAs located in leukemia-associated genomic alterations. Blood. 2011 Jan 13;117(2):595-607.

Starczynowski DT, Kuchenbauer F, Argiropoulos B, Sung S, Morin R, Muranyi A, Hirst M, Hogge D, Marra M, Wells RA, Buckstein R, Lam W, Humphries RK, Karsan A. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med. 2010 Jan;16(1):49-58.

Susan Thompson, PhD

leads a translational research program dedicated to identifying juvenile idiopathic arthritis (JIA) genetic risk factors and disease-specific gene expression patterns to help understand the causes of JIA and the mechanisms of disease pathogenesis. This work has the long-term goal of developing molecular definitions of disease that can be used to improve diagnosis and response to therapy in JIA.
Visit the Thompson Lab.

513-636-3899 susan.thompson@cchmc.org

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Susan Thompson, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-3899

Fax 513-636-3328

Email susan.thompson@cchmc.org

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Molecular basis of juvenile rheumatoid arthritis; large-scale integrative analysis of gene expression, polymorphism and other genomic data with clinical data

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Biography

Susan Thompson, PhD, has research interests that span both genetic and functional genomic studies of juvenile rheumatoid arthritis (JRA) to advance the understanding of the causes and mechanisms of disease pathogenesis. A genome-wide screen for JRA susceptibility traits has been completed and defined several regions for linkage mapping and candidate gene analysis. In addition, complementary approaches that measure global gene expression patterns using DNA microarrays are also being used to understand the molecular basis for disease.

PhD: University of Tennessee Center for Health Sciences, Memphis, TN, 1988.

Fellowship: Immunology, St. Jude Children's Research Hospital, Memphis, TN, 1988-1991.

Fellowship: Molecular Genetics, University of Cincinnati, Cincinnati, OH, 1991-1994.

Thompson SD, Sudman M, Ramos PS, Marion MC, Ryan M, Tsoras M, Weiler T, Wagner M, Keddache M, Haas JP, Mueller C, Prahalad S, Bohnsack J, Wise CA, Punaro M, Zhang D, Rosé CD, Comeau ME, Divers J, Glass DN, Langefeld CD. The susceptibility loci juvenile idiopathic arthritis shares with other autoimmune diseases extend to PTPN2, COG6, and ANGPT1. Arthritis Rheum. 2010 Nov;62(11):3265-76.

Barnes MG, Grom AA, Thompson SD, Griffin TA, Luyrink LK, Colbert RA, Glass DN. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010 Nov;62(11):3249-58.

Thompson SD, Barnes MG, Griffin TA, Grom AA, Glass DN. Heterogeneity in juvenile idiopathic arthritis: impact of molecular profiling based on DNA polymorphism and gene expression patterns. Arthritis Rheum. 2010 Sep;62(9):2611-5.

Hinze CH, Fall N, Thornton S, Mo JQ, Aronow BJ, Layh-Schmitt G, Griffin TA, Thompson SD, Colbert RA, Glass DN, Barnes MG, Grom AA. Immature cell populations and an erythropoiesis gene-expression signature in systemic juvenile idiopathic arthritis: implications for pathogenesis. Arthritis Res Ther. 2010;12(3):R123.

Barnes MG, Grom AA, Thompson SD, Griffin TA, Pavlidis P, Itert L, Fall N, Sowders DP, Hinze CH, Aronow BJ, Luyrink LK, Srivastava S, Ilowite NT, Gottlieb BS, Olson JC, Sherry DD, Glass DN, Colbert RA. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009 Jul;60(7):2102-12.

Griffin TA, Barnes MG, Ilowite NT, Olson JC, Sherry DD, Gottlieb BS, Aronow BJ, Pavlidis P, Hinze CH, Thornton S, Thompson SD, Grom AA, Colbert RA, Glass DN. Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum. 2009 Jul;60(7):2113-23.

Zhang K, Biroschak J, Glass DN, Thompson SD, Finkel T, Passo MH, Binstadt BA, Filipovich A, Grom AA. Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis is associated with MUNC13-4 polymorphisms. Arthritis Rheum. 2008 Sep;58(9):2892-6.

Chaudhari M, Moroldo MB, Shear E, Hillard P, Thompson SD, Lan D, Huang B, Brunner HI, Glass DN. Impaired reproductive fitness in mothers of children with juvenile autoimmune arthropathies. Rheumatology (Oxford). 2006 Oct;45(10):1282-7.

Phelan JD, Thompson SD. Genomic progress in pediatric arthritis: recent work and future goals. Curr Opin Rheumatol. 2006 Sep;18(5):482-9.

Phelan JD, Thompson SD, Glass DN. Susceptibility to JRA/JIA: complementing general autoimmune and arthritis traits. Genes Immun. 2006 Jan;7(1):1-10.

Stephen N. Waggoner, PhD

is a viral immunologist whose lab studies immune regulatory mechanisms that control pathogenesis of disease. The lab uses viruses and bacteria to probe immune functions associated with disease in mice. Interests currently focus on a novel regulatory role of natural killer (NK) cells that influences vaccine efficacy, autoimmune disease, chronic viral infections, and immune dysfunction in the elderly.

513-803-4607 stephen.waggoner@cchmc.org

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Stephen N. Waggoner, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-4607

Email stephen.waggoner@cchmc.org

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Viral immunology; natural killer cells; immunoregulation; vaccines; autoimmunity; immune dysfunction in aging.

Visit the Waggoner Lab.

Biography

Stephen Waggoner, PhD, is an assistant professor in the Center for Autoimmune Genomics and Etiology (CAGE) within the Division of Rheumatology at Cincinnati Children's Hospital Medical Center within the UC Department of Pediatrics. Dr. Waggoner received his PhD from the University of Virginia, conducted postdoctoral research at the University of Massachusetts Medical School, and joined the faculty at Cincinnati Children’s in 2013. He has garnered international recognition for his discovery that natural killer (NK) cells play a crucial regulatory role during persistent virus infection involving suppression of virus-specific T cell responses. His lab continues to explore the relevance of this phenomenon to chronic infection, vaccine efficacy, autoimmune disease, and age-associated immune dysfunction.

BA: St. Mary's College of Maryland, St. Mary's City, MD, 2000.

PhD: University of Virginia, Charlottesville, VA, 2007.

Post Doc: University of Massachusetts Medical School, Worcester, MA.

Severa M, Islam SA, Waggoner SN, Jiang Z, Kim ND, Ryan G, Kurt-Jones E, Charo I, Caffrey DR, Boyartchuk VL, Luster AD, Fitzgerald KA. The transcriptional repressor BLIMP1 curbs host defenses by suppressing expression of the chemokine CCL8. The Journal of Immunology. 2014; 192(5):2291-304.

Waggoner SN, Daniels KA, Welsh RM. Therapeutic depletion of natural killer cells controls persistent infection. Journal of Virology. 2014; 88(4):1953-60.

Cornberg M, Kenney LL, Chen AT, Waggoner SN, Kim SK, Dienes HP, Welsh RM, Selin LK. Clonal exhaustion as a mechanism to protect against severe immuno-pathology and death from an overwhelming CD8 T cell response. Frontiers in Immunology. 2013; 4:475.

Welsh RM, Waggoner SN. NK cells controlling virus-specific T cells: Rheostats for acute vs. persistent infections. Virology. 2013; 435(1):37-45. Review.

Waggoner SN, Kumar V. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection. Frontiers in Immunology. 2012; 3:377. Review.

Waggoner SN, Cornberg M, Selin LK, Welsh RM. Natural killer cells act as rheostats modulating anti-viral T cells. Nature. 2011; 481(7381):394-398.
This paper is “Faculty of 1000 recommended.”

Rathinam VA, Jiang Z, Waggoner SN, Sharma S, Cole LE, Waggoner L, Vanaja SK, Monks BG, Ganesan S, Latz E, Hornung V, Vogel SN, Szomolanyi-Tsuda E, Fitzgerald KA. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nature Immunology. 2010; 11(5):395-402.
This paper is “Faculty of 1000 recommended.”

Waggoner SN, Taniguchi RT, Mathew PA, Kumar V, Welsh RM. Absence of mouse 2B4 promotes NK cell–mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. Journal of Clinical Investigation. 2010; 120(6): 1925-38.

Waggoner SN, Hall CH, Hahn YS. HCV core protein interaction with gC1q receptor inhibits Th1 differentiation of CD4+ T cells via suppression of dendritic cell IL-12 production. Journal of Leukocyte Biology. 2007; 82(6):1407-1419.

Waggoner SN, Cruise MW, Kassel R, Hahn YS. gC1q receptor ligation selectively down-regulates human interleukin-12 production through activation of the phosphoinositide 3-kinase pathway. Journal of Immunology. 2005; 175(7):4706-4714.

Grants

Effect of aging on natural killer cell regulation of T cells in viral pathogenesis. Principal Investigator. Ellison Medical Foundation New Scholar in Aging. July 2012-July 2016.

A revolutionary vaccine approach to prevent HIV infection in substance abuse. Principal Investigator. National Institute on Drug Abuse (NIDA) Avant-Garde Award For HIV/AIDS Research. June 2014-May 2019.

Yui-Hsi Wang, PhD

investigates the mechanisms that govern the plasticity of tissue resident TH2 memory / effector cells in the airway and gut. Particularly interested in understanding how inflammatory mediators, such as IL-1b, IL-33 and IL-25, regulate the development of IL-17-producing TH2 or IL-9-producing TH2 cells during airway or gastrointestinal allergic inflammation, respectively.

513-803-2193 yui_hsi.wang@cchmc.org

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Yui-Hsi Wang, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-2193

Fax 513-636-3310

Email yui_hsi.wang@cchmc.org

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Asthma; food allergy; T cell biology

PhD: University of Alabama, Birmingham, AL, 2001.

Wang YH, Voo KS, Liu B, Chen CY, Uygungil B, Spoede W, Bernstein JA, Huston DP, Liu YJ. A novel subset of CD4(+) T(H)2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma. J Exp Med. 2010 Oct 25;207(11):2479-91.

Shaw J, Wang YH, Ito T, Arima K, Liu YJ. Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70. Blood. 2010 Apr 15;115(15):3051-7.

Wang YH, Liu YJ. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin Exp Allergy. 2009 Jun;39(6):798-806.

Voo KS, Wang YH, Santori FR, Boggiano C, Wang YH, Arima K, Bover L, Hanabuchi S, Khalili J, Marinova E, Zheng B, Littman DR, Liu YJ. Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4793-8.

Lu N, Wang YH, Wang YH, Arima K, Hanabuchi S, Liu YJ. TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis. J Exp Med. 2009 Sep 28;206(10):2111-9.

Esashi E, Wang YH, Perng OA, Qin XF, Hennighausen L, Liu YJ, Watowich SS. Differential regulation of plasmacytoid and conventional dendritic cell development by GM-CSF through STAT5. Immunity. 2008;28:1-12.

Wang YH, Liu YJ. The IL-17 cytokine family and their role in allergic inflammation. Curr Opin Immunol. 2008 Dec;20(6):697-702.

Wang YH, Liu YJ. OX40-OX40L interactions: a promising therapeutic target for allergic diseases? J Clin Invest. 2007 Dec;117(12):3655-7.

Wang YH, Angkasekwinai P, Meng Q, Lu N, Voo KS, Arima K, Hanabuchi S, Corrigan CG, Lee T, Dong C, Huston DR, Yao Z, Ying S, and Liu YJ. IL-25 mediated cross talk between eosinophils and TSLP-DC-activated TH2 memory cells augments allergic immune responses. J. Exp. Med. 2007;204(8): 1837-1847.

Ito T, Wang YH, Duramad O, Hanabuchi S, Perng OA, Gilliet M, Qin FX, Liu YJ. OX40 ligand shuts down IL-10-producing regulatory T cells. Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13138-43.

Sing Sing Way, MD, PhD Pauline and Lawson Reed Chair, Division of Infectious Diseases

is an infectious disease physician-scientist. He cares for infants and children with infection related illness, and provides consultation in the diagnosis and prevention diseases caused by communicable agents. Dr. Way supervises an active basic research laboratory that uses basic immunological approaches to investigate ways to boost host defense and protection against infection. If you have interest in this work, please contact Dr. Way.

513-636-7603 singsing.way@cchmc.org

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Sing Sing Way, MD, PhD

Pauline and Lawson Reed Chair, Division of Infectious Diseases

Academic Affiliations

Associate Professor, UC Department of Pediatrics

Phone 513-636-7603

Email singsing.way@cchmc.org

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Infectious diseases; prenatal infection; immunology

Biography

Dr. Way is an infectious disease physician-scientist. He cares for infants and children with infection related illness, and provides consultation in the diagnosis and prevention diseases caused by communicable agents. Dr. Way supervises an active basic research laboratory that uses basic immunological approaches to investigate ways to boost host defense and protection against infection. Ongoing projects investigate the immune basis responsible for enhanced susceptibility to infection during pregnancy, the immune pathogenesis of pregnancy complications that occur with maternal infection, and the basic signals required for stimulating immune cell activation.

Dr. Way trained in the combined MD/PhD program at the Albert Einstein College of Medicine, pediatric residency at the University of California San Francisco, and infectious disease fellowship at the University of Washington. During fellowship training, Dr. Way began investigating the basic immunology and immune pathogenesis of infectious diseases relevant to human, and in particular, infant and child health.

Dr. Way’s research has been supported by the National Institutes of Health since 2006. Dr. Way’s research has been described in many publications in numerous prestigious scientific journals including Nature, Cell Host & Microbe, PLoS Pathogens, and The Journal of Immunology. The past and ongoing work has also been recognized by numerous prestigious awards including the Infectious Diseases Society of America Wyeth Young Investigator Award, a Basil O’ Conner Award from the March of Dimes Foundation, and the Investigator in Pathogenesis of Infectious Diseases award from the Burroughs Wellcome Fund.

MD PhD: Albert Einstein College of Medicine, Bronx, NY, 1999.

Residency: University of California San Francisco, San Francisco, CA, 2001.

Fellowship: University of Washington, Seattle, WA, 2004.

Rowe JH, Ertelt JM, Xin L, Way SS. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature. 490: 102-106. 2012.

Rowe JH, Ertelt JM, Xin L, Way SS. Listeria monocytogenes cytoplasmic entry induces fetal wastage by disrupting maternal Foxp3+ regulatory T cell-sustained fetal tolerance. PLoS Pathog. 8: e1002873. 2012.

Rowe JH, Ertelt JM, Way SS. Innate IFN-g is essential for Programmed death ligand-1-mediated T cell stimulation following Listeria monocytogenes infection. J Immunol. 189: 876-84. 2012.

Rowe JH, Ertelt JM, Way SS. Foxp3+ regulatory T cells, immune stimulation, and host defense against infection. Immunology. 136:1-10. 2011.

Ertelt JM, Johanns TM, Mysz MA, Nanton MR, Rowe JH, Aguilera MN, Way SS. Selective culling of high avidity antigen-specific CD4+ T cells after virulent Salmonella infection. Immunology. 134: 487-97. 2011.

Ertelt JM, Rowe JH, Mysz MA, Singh C, Roychowdhury M, Aguilera MN, Way SS. Foxp3+ regulatory T cells impede the priming of protective CD8+ T cells. J Immunol. 187: 2569-77. 2011.

Rowe JH, Ertelt JM, Aguilera MN, Farrar MA, Way SS. Foxp3+ regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens. Cell Host Microbe. 10:54-64. 2011.

Johanns TM, Law CY, Kalekar LA, O’Donnell H, Ertelt JM, Rowe JH, Way SS. Early eradication of persistent Salmonella infection primes antibody-mediated protective immunity to recurrent infection. Microbes Infect. 13: 322-330. 2011.

Han JY, Hanson DC, Way SS. Herpes Zoster and meningitis due to reactivation of varicella vaccine virus in a immunocompetent child. Pediatr Infect Dis J. 30:266-268. 2011.

Ertelt JM, Johanns TM, Rowe JH, Way SS. IL-21-independent pathogen-specific CD8+ T cell expansion, and IL-21-dependnent suppression of CD4+ T cell IL-17 production. Immunology. 131: 183-191. 2010.

Grants

Maternal regulatory T cells control the immune pathogenesis of prenatal infection. Principal Investigator in the Pathogenesis of Infectious Disease. Burroughs Wellcome Fund. 2012-2017.

The immune pathogenesis of prenatal Listeria monocytogenes infection. Principle Investigator. National Institute of Allergy and Infectious Diseases (NIAID). 2012-2017. R01-AI100934.

Timothy E. Weaver, MS, PhD Co-Director, Division of Pulmonary Biology

focuses on the identification of cytoprotective pathways that mediate adaptation to genetic and environmental stresses in the pulmonary epithelium. These molecular pathways play a critical role in preventing or slowing the progression of chronic lung disease and may provide novel targets for therapeutic intervention.
Visit the Weaver Lab.

513-636-7223 tim.weaver@cchmc.org

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Timothy E. Weaver, MS, PhD

Co-Director, Division of Pulmonary Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-7223

Fax 513-636-7868

Email tim.weaver@cchmc.org

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Lung development; chaperone biology and diseases of protein misfolding; pulmonary fibrosis; asthma; respiratory distress syndrome; acute and chronic lung disease

Visit the Weaver Lab.

Biography

Dr. Weaver has a long-standing interest in lung development and disease. His early work with Dr. Whitsett uncovered the function of surfactant proteins SP-B and SP-C, a discovery that has profoundly influenced the treatment of respiratory distress syndrome and survival of pre-term infants worldwide. His current research is focused to the molecular pathways (ER stress and autophagy) that link mutations in the SFTPC gene (encoding surfactant protein C) to development of interstitial lung disease (ILD) in both children and adults. His work has been continuously funded by the National Institutes of Health since 1986, including a MERIT (R37) award from the National Heart, Lung and Blood Institute (2001-2011).

Dr. Weaver has trained 14 graduate students in the past 15 years and is the past director of the Molecular and Developmental Biology Graduate Program. During the same period of time he has trained 11 postdoctoral fellows, eight of whom are current faculty members at institutions in the US, Germany, France, Japan and UK.

BS: Biology, Bob Jones University, Greenville, SC, 1975.

MS: Embryology, Hahnemann Medical College, Philadelphia, PA, 1979.

PhD: Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 1983.

Postdoc: Molecular Biology, University of Cincinnati College of Medicine, Cincinnati, OH, 1986.

Hahn DR, Na CL, Weaver TE. Reserve autophagic capacity in alveolar epithelia provides a replicative niche for influenza A virus. Am J Respir Cell Mol Biol. 2014 Sep;51(3):400-12.

Fritz JM, Dong M, Apsley KS, Martin EP, Na CL, Sitaraman S, Weaver TE. Deficiency of the BiP cochaperone ERdj4 causes constitutive endoplasmic reticulum stress and metabolic defects. Mol Biol Cell. 2014 Feb; 25(4):431-40.

Ridsdale R, Na CL, Xu Y, Greis KD, Weaver T. Comparative proteomic analysis of lung lamellar bodies and lysosome-related organelles. PLoS One. 2011 26;6(1):e16482.

Yang L, Johansson J, Ridsdale R, Willander H, Fitzen M , Akinbi HT, Weaver TE. Surfactant Protein B Propeptide Contains a Saposin-Like Protein Domain with Antimicrobial Activity at Low pH. J Immunol. 2010 Jan 15;184(2):975-83.

Dong M, Bridges JP, Apsley K, Xu Y, Weaver TE. ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C. Mol Biol Cell. 2008 Jun;19(6):2620-30.

Korfei M, Ruppert C, Mahavadi P, Henneke I, Markart P, Koch M, Lang G, Fink L, Bohle RM, Seeger W, Weaver TE, Guenther A. Epithelial endoplasmic reticulum stress and apoptosis in sporadic idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 15;178(8):838-46.

Nash JA, Ballard TN, Weaver TE, Akinbi HT. The peptidoglycan-degrading property of lysozyme is not required for bactericidal activity in vivo. J Immunol. 2006 Jul 1;177(1):519-26.

Johansson H, Nordling K, Weaver TE, Johansson J. The Brichos domain-containing C-terminal part of pro-surfactant protein C binds to an unfolded poly-val transmembrane segment. J Biol Chem. 2006 Jul 28;281(30):21032-9.

Bridges JP, Xu Y, Na CL, Wong HR, Weaver TE. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. J Cell Biol. 2006 Jan 30;172(3): 395-407.

Melton KR, Nesslein LL, Ikegami M, Tichelaar JW, Clark JC, Whitsett JA, Weaver TE. SP-B deficiency causes respiratory failure in adult mice. Am J Physiol Lung Cell Mol Physiol. 2003 Sep;285(3):L543-9.

Grants

Stard7, A Novel Inhibitor Of Allergic Lung Disease. Principal Investigator. National Institutes of Health. Dec 2013-Nov 2017. R01-HL122130.

Matthew T. Weirauch, PhD

is a computational biologist. His lab seeks to understand the mechanisms of gene transcriptional regulation. Current projects focus on characterizing transcription factor binding specificities, and developing methods for modeling their interactions with DNA, both in vitro and in vivo. His lab applies insights from basic research on transcription factor-DNA interactions to study the mechanisms underlying complex diseases.

Visit the Weirauch Lab.

513-803-9078 matthew.weirauch@cchmc.org

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Matthew T. Weirauch, PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-9078

Email matthew.weirauch@cchmc.org

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Transcription factors; transcriptional regulation; functional genomics; genome analysis

Visit the Weirauch Lab.

Biography

Matthew T. Weirauch, PhD, a faculty member in the Center for Autoimmune Genomics and Etiology (CAGE), is a computational biologist with special emphasis on genomic approaches for studying transcription factor (TF) interactions with DNA, and how genetic variation proximal to these interactions contributes to human diseases. He recently spearheaded large-scale efforts for the experimental and computational determination of sequence binding motifs for eukaryotic TFs (Weirauch et al., Cell, 2014), and RNA binding proteins (Nature co-first author, 2013). He has also been involved in numerous high-profile genomics efforts, including an evaluation of algorithms for TF-DNA recognition (Weirauch et al., Nature Biotech, 2013), and the largest genetic interaction studies performed to date in both C. elegans (Byrne et al., Journal of Biology, 2007) and S. cerevisiae (Costanzo et al., Science, 2010). Recent work in his group focuses on how disease-associated genomic regions affect TF binding, and how these alterations affect disease onset and progression (Wang et al., Mol Cancer., 2010; Qian et al., Pediatr Blood Cancer, 2014; Kottyan et al., Nature Genetics, 2014; Martin et al., Circulation: Cardiovascular Genetics, 2014; Fang et al., Cell Reports, 2014).

The long-term goal of Dr. Weirauch's lab is to create an accurate computational system for predicting TF and RNA binding protein interactions with the genome/transcriptome, and for understanding the effects of genetic variations on these interactions. As it continues to mature, they are applying this system to predict the effects of genetic variants that are strongly associated with several human diseases. Long-term, they envision that this system will be used for personalized medicine-based approaches – given the genome sequence of a patient, it will produce a prioritized list of genetic variants likely to contribute to disease onset via alterations to protein binding events.

Postdoctoral Fellow: University of Toronto (Donnelly Center for Cellular and Biomolecular Research), Toronto, Ontario, Canada.

PhD: Bioinformatics, University of California Santa Cruz, Santa Cruz, California.

BSc: Computer Science, Pennsylvania State University, University Park, PA.

Weirauch M, Yang A, Albu M, Cote A, Montenegro-Montero A, Drewe P, Najafabadi H, Lambert S, Mann I, Cook K, Zheng H, Goity A, van Bakel H, Lozano J, Galli M, Lewsey M, Huang E, Mukherjee T, Chen X, Reece-Hoyes J, Govindarajan S, Shaulsky G, Walhout AJM, Bouget F, Ratsch G, Larrondo L, Ecker J, Hughes T. Determination and inference of eukaryotic transcription factor sequence specificity. Cell. 2014 Sep 11;158(6):1431-1443.

Makashir S, Kottyan L, Weirauch M. Meta-analysis of Differential Gene Co-expression: Application to Lupus. Pacific Symposium on Biocomputing. 2014.

Kottyan L, Davis B, Sherrill J, Lui K, Rochman M, Kaufman K, Weirauch M, Vaughn S, Lazaro S, Rupert A, Kohram M, Stucke E, Kemme K, Magnusen A, He H, Dexheimer P, Mukkada V, Putnam P, Strauss A, Abonia JP, Martin L, Harley J, Rothenberg M. Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease. Nat Genet. 2014 Aug;46(8):895-900.

Sullivan A, Arsovski A, Lempe J, Bubb K, Weirauch M, et al. Mapping and Dynamics of Regulatory DNA and Transcription Factor Networks in A. thaliana. Cell Reports. 2014 Sep 10.

Kottyan L, Zoller E, Bene J, Lu X, Kelly J, Rupert A, Lessard C, Vaughn S, Marion M, Weirauch M, et al. The IRF5-TNPO3 association with systemic lupus erythematosus (SLE) has two components that other autoimmune disorders variably share. Hum Mol Genet. 2014 Sep 8.

Weirauch M, Cote A, Norel R, Annala M, Zhao Y, Riley T, Saez-Rodriguez J, Cokelaer T, Vedenko A, Talukder S, DREAM5 Consortium, et al. Evaluation of methods for modeling transcription factor sequence specificity. Nature Biotechnology. 2013 Jan 27;31(2):126-34.

Ray D*, Kazan H*, Cook K*, Weirauch M*, Najafabadi H*, Li X, Gueroussov S, Albu M, Zheng H, Yang A, Na H, Irimia M, Matzat L, Dale R, Smith S, Yarosh C, Kelly S, Nabet B, Mecenas D, Li W, Laishram R, Qiao M, Lipshitz H, Piano F, Corbett A, Carstens R, Frey B, Anderson R, Lynch K, Penalva L, Lei E, Fraser A, Blencowe B, Morris Q, Hughes T. A compendium of RNA binding motifs for decoding gene regulation. Nature. 2013 Jul 10;499(7457):172-177. *co-first authors.

Costanzo M, Baryshnikova A, Bellay J, Kim Y, Spear E, Sevier C, Ding H, Koh J, Toufighi K, Mostafavi S, Prinz J, St Onge R, VanderSluis B, Makhnevych T, Vizeacoumar F, Alizadeh S, Bahr S, Brost R, Chen Y, Cokol M, Deshpande R, Li Z, Lin Z, Liang W, Marback M, Paw J, San Luis B, Shuteriqi E, Tong A, van Dyk N, Wallace I, Whitney J, Weirauch M, Zhong G, Zhu H, Houry W, Brudno M, Ragibizadeh S, Papp B, Pál C, Roth F, Giaever G, Nislow C, Troyanskaya O, Bussey H, Bader G, Gingras A, Morris Q, Kim P, Kaiser C, Myers C, Andrews B, Boone C. The genetic landscape of a cell. Science. 2010 Jan 22;327(5964):425-31.

Byrne A, Weirauch M, Wong V, Koeva M, Dixon S, Stuart J, Roy P. A global analysis of genetic interactions in Caenorhabditis elegans. J Biol. 2007;6(3):8.

ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature. 2007 Jun 14;447(7146):799-816.

Grants

Viral transcription factor interactions with disease-associated genetic variants. Principal Investigator. Trustee Award, Cincinnati Children's. Jul 2014-Jun 2016.

Translational Genomics Analysis Core. Co-Investigator. NIH/NCRR CCTST T1 Pilot, Cincinnati Children's. Jul 2014-Jun 2016.

Decoding C2H2 Zinc Fingers. Collaborator. Canadian Institutes of Health Research (CIHR) Operating Grant. Oct 2013-Sep 2016.

Susanne Wells, PhD Director, Epithelial Carcinogenesis and Stem Cell Program

focuses on new targets of the HPV E6/E7 oncogenes, and characterizing these as potential risk factors for HPV infection and transformation. Research approaches include bioinformatics; analyses of primary, transformed and 3D cell culture systems; and mouse tumor models to facilitate translational endeavors.
Visit the Wells Lab.

513-636-5986 susanne.wells@cchmc.org

High Res

Susanne Wells, PhD

Director, Epithelial Carcinogenesis and Stem Cell Program

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-5986

Fax 513-636-3549

Email susanne.wells@cchmc.org

Show All

Squamous cell carcinoma; mechanisms by which the HPV oncogenes subvert the host cell machinery to promote abnormal cell growth and cancer; role of specific cellular HPV targets in viral replication and cellular transformation

Visit the Wells Lab.

Biography

Susanne Wells graduated from the University of Konstanz, Germany, with a degree in biology. She completed her PhD in molecular biology at the State University of Stony Brook, NY, and her postdoctoral fellowship at Harvard Medical School, MA. Dr. Wells moved to Cincinnati Children's Hospital Medical Center in 2002 to study human papillomavirus infection and associated carcinogenesis.

BS: Biology, University of Konstanz, Germany, 1992.

PhD: Molecular Genetics, State University of Stony Brook, NY, 1997.

Postdoctoral Fellowship: Molecular Virology, Harvard Medical School, Boston, MA.

Bahassi M, Li YQ, Wise-Draper TM, Deng L, Wang J, Darnell CN, Wilson KM, Wells SI, Stambrook PJ. Rixe O. A patient-derived somatic mutation in the epidural growth factor ligand-binding domain confers increased sensitivity to cetuximab in heck and neck cancer. European J Cancer. 2013 Jul:49(10):2345-55.

Privette Vinnedge LM, Ho SM. Wikenheiser-Brokamp KA, Wells SI. The DEK oncogene is a target of steroid hormone receptor signaling in breast cancer. PLoS One. 2012;7(10):e46985.

Hoskins EE, Morreale RJ, Werner SP, Higginbotham JM, Laimins LA, Lambert PF, Brown DR, Gillison ML, Nuovo GJ, Witte DP, Kim MO, Davies SM, Mehta PA, Butsch Kovacic M, Wikenheiser-Brokamp KA, Wells SI. The Fanconi anemia pathway limits human papillomavirus replication. J Virol. 2012 Aug;86(15);8131-8.

Wise-Draper TM, Draper DJ, Gutkind JS, Molinolo AA, Wikenheiser-Brokamp KA, Wells SI, Future directions and treatment strategies for head and neck squamous cell carcinomas. Transl Res. 2012 Sep;160(3):167-77.

Morrison MA, Morreale RJ, Akunuru S, Kofron M, Zheng Y, Wells SI. Targeting the human papillomavirus E6 and E7 oncogenes through expression of the BPV1 E2 protein stimulates cellular motility. J Virol. 2011 Oct;85(20):10487-98.

Myers KC, Bleesing JJ, Davies SM, Zhang X, Martin LJ, Mueller R, Harris RE, Filipovich AH, Kovacic MB, Wells SI, Mehta PA. Impaired immune function in children with Fanconi anaemia. Br J Haematol. 2011 Jul;154(2):234-40.

Kavanaugh GM, Wise-Draper TM, Morreale RJ, Morrison MA, Gole B, Schwemberger S, Tichy ED, Lu L, Babcock GF, Wells JM, Drissi R, Bissler JJ, Stambrook PJ, Andreassen PR, Wiesmuller L, Wells SI. The human DEK oncogene regulates DNA damage response signaling and repair. Nucl Acids Res. 2011 Sep 1;39(17):7465-76.

Privette Vinnedge LM, McClaine R, Wagh PK, Wikenheiser-Brokamp KA, Waltz SE, Wells SI. The human DEK oncogene stimulates β-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene. 2011 Jun 16;30:2741-52.

Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Toile K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 2011 Feb 3;470(733):105-9.

Meyer SE, Peace BE, Bahassi el M, Kavanaugh GM, Wagh PK, Robbins SB, Yin M,Wells SI, Zinser GM, Stambrook PJ, Waltz SE. Chk2*1100delC Acts in synergy with the Ron receptor tyrosine kinase to accelerate mammary tumorigenesis in mice. Cancer Lett. 2010 Oct 28;296(2):186-93.

Grants

Role and regulation of the human DEK proto-oncogene. Principal Investigator. National Institutes of Health. 2012-2017. 2R01 CA116316.

Yi Zheng, PhD Director, Experimental Hematology and Cancer Biology

studies the function and signaling mechanism of the Rho family GTPases and the mTor metabolic pathway, particularly in stem cell and cancer stem cell regulation.
Visit the Zheng Lab.

513-636-0595 yi.zheng@cchmc.org

High Res

Yi Zheng, PhD

Director, Experimental Hematology and Cancer Biology

Katherine Stewart Waters Endowed Chair

Co-Director, Cancer and Blood Diseases Institute

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-0595

Fax 513-636-3768

Email yi.zheng@cchmc.org

Show All

Using transgenic and gene targeted mouse models to study the physiological and pathological roles of Rho GTPases and their regulators in hematopoiesis, neurogenesis, lung cancer development and small intestinal stem cell regulations mechanism based, rational design of small molecule inhibitors targeting Rho GTPase signaling modules and pathologic functions in cancer and blood diseases; mouse model studies of mTor signaling function in hematopoietic stem cells and small intestinal stem cells.

Visit the Zheng Lab.

BS: Tsinghua University, Beijing, China, 1986.

MS: Cornell University, Ithaca, NY, 1988.

PhD: Cornell University, Ithaca, NY, 1991.

Postdoctoral Fellow: Cornell University, Ithaca, NY, 1995.

View All PubMed Publications

Kesarwani M, Huber E, Kincaid Z, Evelyn CR, Biesiada J, Rance M, Thapa MB, Shah NP, Meller J, Zheng Y, Azam M. Targeting substrate-site in Jak2 kinase prevents emergence of genetic resistance. Sci Report. 2015. In press.

Konstantinidis DG, Giger KM, Risinger M, Pushkaran S, Zhou P, Dexheimer P, Yerneni S, Andreassen P, Klingmüller U, Palis J, Zheng Y, Kalfa TA. Cytokinesis failure in RhoA-deficient mouse erythroblasts involves actomyosin and midbody dysregulation and triggers p53 activation. Blood. 2015 Jul 30. [Epub ahead of print]

Barry DM, Xu K, Meadows SM, Zheng Y, Norden PR, Davis GE, Cleaver O. Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation. Development. 2015 Aug 7. [Epub ahead of print]

Yang JQ, Kalim KW, Li Y, Zhang S, Hinge A, Filippi MD, Zheng Y, Guo F. RhoA orchestrates glycolysis for TH2 cell differentiation and allergic airway inflammation. J Allergy Clin Immunol. 2015 Jun 19. [Epub ahead of print]

Lin Y, Zheng Y. Approaches for targeting Rho GTPases in cancer drug discovery. Expert Opin Drug Discov. 2015 Sep;10(9):991-1010.

Zandvakili I, Davis AK, Hu G, Zheng Y. Loss of RhoA exacerbates, rather than dampens, oncogenic K-Ras induced lung adenoma formation in mice. PLoS One. 2015 Jun 1;10(6):e0127923.

Evelyn CR, Biesiada J, Duan X, Tang H, Shang X, Nelson S, Seibel WL, Meller J, Zheng Y. Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme. J Biol Chem. 2015 May 15;290(20):12879-98.

Mikelis CM, Simaan M, Ando K, Fukuhara S, Sakurai A, Amornphimoltham P, Masedunskas A, Weigert R, Chavakis T, Adams RH, Offermanns S, Mochizuki N, Zheng Y, Gutkind JS. RhoA and ROCK mediate histamine-induced vascular leakage and anaphylactic shock. Nat Commun. 2015 Apr 10;6:6725.

Li J, Zhang L, Chen Z, Xie M, Huang L, Xue J, Liu Y, Liu N, Guo F, Zheng Y, Kong J, Zhang L. Cocaine activates Rac1 to control structural and behavioral plasticity in caudate putamen. Neurobiol Dis. 2015 Mar;75:159-76.

Chang KH, Nayak RC, Roy S, Perumbeti A, Wellendorf AM, Bezold KY, Pirman M, Hill SE, Starnes J, Loberg A, Zhou X, Inagami T, Zheng Y, Malik P, Cancelas JA. Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation. Nat Commun. 2015 Jan 9;6:5914.

Grants