Immunobiology

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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.

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.
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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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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.

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.
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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

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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.

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.

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.
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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

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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.

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

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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.

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.

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.
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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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Specialties

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.

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.

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.

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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Specialties

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.

Rajat Madan, MBBS, PhD Member, Division of Gastroenterology, Hepatology and Nutrition

The Madan Lab studies the role of obesity-associated molecule leptin in controlling host neutrophil responses to Clostridium difficile, the #1 cause of nosocomial infections in the U.S. The lab uses samples (and clinical data) from patients with C. difficile and different murine models (diet-induced obese and leptin receptor mutant mice) of C. difficile infection, to understand the role of leptin signaling in disease pathogenesis and resolution.

513-558-0220 rajat.madan@uc.edu

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Rajat Madan, MBBS, PhD

Member, Division of Gastroenterology, Hepatology and Nutrition

Member, Division of Immunobiology

Academic Affiliations

Assistant Professor, UC Department of Internal Medicine

Phone 513-558-0220

Email rajat.madan@uc.edu

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Specialties

The overall research goal of our laboratory is to better understand the cellular and molecular mechanisms by which nutrition, metabolism, and immune responses to infections are fundamentally linked. Leptin is an adipose tissue-secreted cytokine that sits at the intersection of metabolism and immunity. Interestingly obesity is a state of high serum leptin levels, thus leptin by virtue of its multiple physiologic effects is likely to play an important role in directing inflammation in obese patients as well, who represent a rapidly expanding population demographic worldwide. Clostridium difficile is the #1 cause of healthcare-associated diarrhea in the U.S. In our lab, we are investigating the role of leptin receptor polymorphisms and obesity (as measured by Body Mass Index) in affecting disease susceptibility, severity and disease outcomes in patients with C. difficile infection. In parallel, we are using various leptin transgenic mice and diet-induced obese mice to interrogate the mechanism(s) by which leptin signaling impacts the immune response during C. difficile infections. Our studies (using both human clinical samples and mouse models) have the potential to augment the current treatment paradigm for C. difficile with therapies directed at the host immune response.

MBBS: JLN Medical College, Ajmer, India, 2001.

PhD: Immunology and Developmental Biology, University of Cincinnati, Cincinnati, 2009.

Residency: Internal Medicine, The Christ Hospital, Cincinnati, 2011.

Fellowship: Infectious Diseases, University of Virginia, Charlottesville, 2014.

Certifications: Internal Medicine, 2011; Infectious Diseases, 2014; CTropMed® Program, 2014.

Jose S, Madan R. Neutrophil-mediated inflammation in the pathogenesis of Clostridium difficile infections. Anaerobe. 2016.

Madan R, Petri WA Jr. Role of obesity and adipose tissue-derived cytokine leptin during Clostridium difficile infection. Anaerobe. 2015 Jan 29.

Madan R, Guo X, Naylor C, Buonomo EL, Mackay D, Noor Z, Concannon P, Scully KW, Pramoonjago P, Kolling GL, Warren CA, Duggal P, Petri WA Jr. Role of leptin-mediated colonic inflammation in defense against Clostridium difficile colitis. Infect Immun. 2014 Jan;82(1):341-9.

Naylor C, Burgess S, Madan R, Buonomo E, Razzaq K, Ralston K, Petri WA Jr. Leptin receptor mutation results in defective neutrophil recruitment to the colon during Entamoeba histolytica infection. MBio. 2014 Dec 16;5(6).

Buonomo EL, Madan R, Pramoonjago P, Li L, Okusa MD, Petri WA Jr. Role of interleukin 23 signaling in Clostridium difficile colitis. J Infect Dis. 2013 Sep;208(6):917-20.

Jarrell A, Kawsky J, Johnson T, Voss S, Madan R, Weitkamp T, Wigle P. An interdisciplinary approach to determine schistosomiasis prevalence and administer praziquantel to school-age children in Tanzania. Am J Health Syst Pharm. 2013 Nov 1;70(21):1880-2.

Madan R, Jr WA. Immune responses to Clostridium difficile infection. Trends Mol Med. 2012 Nov;18(11):658-66.

Denning TL, Norris BA, Medina-Contreras O, Manicassamy S, Geem D, Madan R, Karp CL, Pulendran B. Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J Immunol. 2011 Jul 15;187(2):733-47.

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.

Murai M, Turovskaya O, Kim G, Madan R, Karp CL, Cheroutre H, Kronenberg M. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis. Nat Immunol. 2009 Nov;10(11):1178-84.

Grants

Role of leptin in mucosal protection during Clostridium difficile infection. Principal Investigator. NIH. Aug 2014-July 2019.

Regulation of neutrophil recruitment during Clostridium difficile infection by a single nucleotide polymorphism in leptin receptor. Principal Investigator. Department of Medicine, University of Cincinnati. Jan 2016-Dec 2016.

Yrina Rochman, PhD

is focused on elucidating molecular mechanisms of immunological responses. Particularly, on the role of cytokines in the adaptive immune response and T cell differentiation.

yrina.rochman@cchmc.org

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Yrina Rochman, PhD

Academic Affiliations

Instructor, UC Department of Pediatrics

Email yrina.rochman@cchmc.org

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Immunology

Biography

Yrina earned her PhD from the Hebrew University of Jerusalem. She completed her post-doctoral training in molecular immunology at National Institutes of Health in the laboratory of Dr. Warren Leonard, where she published several papers and reviews in high profile peer-reviewed journals. She is a recipient of the Lenfant Biomedical Award from NHLBI, NIH for outstanding research. Her research is focused on elucidating molecular mechanisms of immunological responses.

PhD: Hebrew University of Jerusalem, Israel, 2005.

Post-Doc Fellowship: NHLBI/National Institutes of Health, Bethesda, MD, 2005-2011.

Research Associate: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2012-2013.

Research Instructor: Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 2013-present.