Paul R. Andreassen, PhD
focuses on the relationship of DNA repair and cell cycle checkpoints to the genetic instability that underlies the development of cancer. In particular, he studies basic cellular mechanisms that respond to DNA damage, including breast cancer susceptibility (BRCA) and Fanconi anemia (FA) genes and proteins. Visit the Andreassen Lab.
513-636-0499
paul.andreassen@cchmc.org
Paul R. Andreassen, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsFanconi Anemia; cell cycle check points; genetic instability; replication stress; relationship of DNA repair and chromatin; mitosis; cell biology Visit the Andreassen Lab.
Education and Training
BS: Willamette University, Salem, Oregon, 1984 PhD: University of Washington, Seattle, Washington, 1995
Publications
View PubMed Publications
Du W, Rani R, Sipple J, Schick J, Myers KC, Mehta P, Andreassen PR, Davies SM, Pang Q. The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters. Blood. 2012;119(18): 4142-51. Duan W, Gao L, Zhao W, Leon M, Sadee W, Webb A, Resnick K, Wu X, Ramaswamy B, Cohn DE, Shapiro C, Andreassen PR, Otterson GA, Villalona-Calero MA. Assessment of FANCD2 nuclear foci formation in paraffin-embedded tumors: a potential patient-enrichment strategy for treatment with DNA interstrand crosslinking agents. Trans Res. 2012 [Epub ahead of print]. Sin HS, Barski A, Zhang F, Kartashov AV, Nussenzweig A, Chen J, Andreassen PR, Namekawa SH. RNF8 regulates active epigenetic modifications and escape gene activation from inactive sex chromosomes in post-meiotic spermatids. Genes Dev. 2012 26(24) [Epub ahead of print]. Zhang F, Bick G, Park JY, Andreassen PR. MDC1 and RNF8 function in a pathway that directs BRCA1-dependent localization of PALB2 required for homologous recombination. J. Cell Sci. 2012 [Epub ahead of print]. Ichijima Y, Ichijima M, Lou Z, Nussenzweig A, Camerini-Otero RD, Chen J, Andreassen PR and Namekawa SH. MDC1 directs chromosome-wide silencing of the sex chromosomes in male germ cells. Genes Dev. 2011;25(9):959-71. 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 and Wells SI. The human DEK oncogene regulates DNA damage response signaling and repair. Nucleic Acids Res. 2011 ;39(17):7465-76. Melendez J, Stengel K, Zhou X, Chauchan BK, Debidda M, Andreassen PR, Lang RA and Zheng Y. RhoA GTPase is dispensable for actomyosin regulation but is essential for mitosis in primary mouse embryonic fibroblasts. J. Biol. Chem. 2011;286(17):15132-7. Montes de Oca R, Andreassen PR and Wilson KL. Barrier-to-autointegration factor influences specific histone modifications. Nucleus 2011; 2(6): 580-90. Hayakawa T, Zhang F, Hayakawa N, Ohtani Y, Shinmyozu K, Nakayama J and Andreassen PR. MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks. J. Cell Sci. 2010;127(Pt 7):1124-30. Zhang F, Fan Q, Ren K, Auerbach AD and Andreassen PR. FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses. Chromosoma 2010;119(6):637-49. Pang Q and Andreassen PR. Fanconi anemia proteins and endogenous stresses. Mutat. Res. 2009;668(1-2):42-53. Fan Q, Zhang F, Barrett B, Ren K and Andreassen PR. A role for monoubiquitinated FANCD2 at telomeres in ALT cells. Nucleic Acids Res. 2009;37(6):1740-54. Andreassen PR and Ren K. Fanconi anemia proteins, DNA interstrand crosslink repair pathways, and cancer therapy. Curr. Cancer Drug Targets 2009;9(1):101-17. Zhang F, Fan Q, Ren K and Andreassen PR. PALB2 functionally connects the breast cancer susceptibility proteins BRCA1 and BRCA2. Mol Cancer Res. 2009;7(7):1110-8.
Grants
FANCD2 monoubiquitination in DNA damage responses. Principal Investigator. National Heart, Lung, and Blood Institute. Jul 2008 - Jun 2013. #R01 HL085587.
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Mohammad Azam, PhD
is interested in understanding molecular basis of human cancers, especially hematopoietic malignancies. His research group focuses on understanding the mechanisms of tyrosine kinase regulation, oncogene addiction and the development of cancer stem cells.
513-803-1413
mohammad.azam@cchmc.org
Mohammad Azam, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsLeukemia Research InterestsStructure and function analysis of tyrosine kinases involved in the pathogenesis of leukemia; molecular basis of “oncogene addiction”; modeling of human leukemia in mice using ES and patient derived iPS Cells
Education and Training
PhD: Jawaharlal Nehru University, India.
Post-doc: Whitehead Institute for Biomedical Research at MIT (2001-2003).
Instructor: Children’s Hospital of Boston and Harvard Medical School. (2006-2009).
Publications
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Azam M, Powers JT, Einhorn W, Huang WS, Shakespeare WC, Zhu X, Dalgarno D, Clackson T, Sawyer TK, Daley GQ. AP24163 inhibits the gatekeeper mutant of BCR-ABL and suppresses in vitro resistance. Chem Biol Drug Des. 2010 Feb;75(2):223-7. Zhang J, Adrián FJ, Jahnke W, Cowan-Jacob SW, Li AG, Iacob RE, Sim T, Powers J, Dierks C, Sun F, Guo GR, Ding Q, Okram B, Choi Y, Wojciechowski A, Deng X, Liu G, Fendrich G, Strauss A, Vajpai N, Grzesiek S, Tuntland T, Liu Y, Bursulaya B, Azam M, Manley PW, Engen JR, Daley GQ, Warmuth M, Gray NS. Targeting Bcr-Abl by combining allosteric with ATP-binding-site inhibitors. Nature. 2010 Jan 28;463(7280):501-6. Nardi V, Azam M, Neverias O, Daley GQ. Immune-Mediated Protection Against BCR/ABL-Induced Leukemia: A Common Pathway Shared between IRF8/ICSBP and IFN alpha and beta. Blood. 2009.
Viswanathan SR, Powers JT, Einhorn W, Hoshida Y, Ng TL, Toffanin S, O'Sullivan M, Lu J, Phillips LA, Lockhart VL, Shah SP, Tanwar PS, Mermel CH, Beroukhim R, Azam M, Teixeira J, Meyerson M, Hughes TP, Llovet JM, Radich J, Mullighan CG, Golub TR, Sorensen PH, Daley GQ. Lin28 promotes transformation and is associated with advanced human malignancies. Nature Genetics. 2009 Jul;41(7):843-8. Azam M, Seeliger M, Gray S, Kuriyan J, Daley GQ. Activation of tyrosine kinases by the mutation of gatekeeper residue. Nat Struct Mol Biol. 2008 Oct;15(10):1109-18.
Raz T, Nardi V, Azam M, Cortes J, Daley GQ. Farnesyl transferase inhibitor resistance probed by target mutagenesis. Blood. 2007 Sep 15;110(6):2102-9. Azam M, Nardi V, Shakespeare WC, Metcalf CA 3rd, Bohacek RS, Wang Y, Sundaramoorthi R, Sliz P, Veach DR, Bornmann WG, Clarkson B, Dalgarno DC, Sawyer TK, Daley GQ. Activity of dual SRC-ABL inhibitors highlights role of BCR/ABL kinase dynamics in drug resistance. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9244-9. Azam M, and Daley GQ. Anticipating Clinical Resistance to Target-directed Agents: BCR-ABL an example. Molecular Diagnosis and Therapy. 2006;10(2):67-76.
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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
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 Information
Professor, UC Department of Pediatrics
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Specialties
Education and Training
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.
Publications
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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. Rational Design of a Vav/Rac Inhibitor as a New Therapy for High-Risk B-ALL. Principal Investigator. Leukemia & Lymphoma Society of North America. Oct 2012 – Sep 2015. Cincinnati Excellence in Molecular Hematology: Cell Analysis and Sorting Core, NIH/NIDDK. Co-investigator. (Flow Cytometry Core Co-PI). Sep 2010 – Jun 2015. #P30DK090971-01. Rac GTPase Inhibition in Chronic Myelogenous Leukemia. Principal Investigator. National Institutes of Health. Apr 2009 – Feb 2014. #R01 HL 087159. Improving Hematopoietic Stem Cell Mobilization by the EGFR inhibitor Erlotinib. Co-Principal Investigator with Hartmut Geiger. NIH/NHLBI. Feb 2011 – Jan 2013. #R43HL108403-01. Connexin-43 in Bone Marrow Failure After Cancer-Related Chemotherapy. Principal Investigator. Heimlich Institute. Apr 2010 – Mar 2013.
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Lionel M.L. Chow, MD, PhD
studies high grade gliomas, which are aggressive brain tumors in adults and children with limited treatment options. Using a combination of novel and robust laboratory models coupled with the study of human tumor material, the lab’s goals are to better understand the cellular origins and molecular underpinnings of these diseases in order to design and test novel therapies that will hopefully improve patient outcome. Visit the Chow Lab
513-803-1369
lionel.chow@cchmc.org
Lionel M.L. Chow, MD, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsPediatric neuro-oncology Research InterestsMouse models for glioma; molecular profiling of tumor mutations; biomarkers of tumor progression; novel therapeutic agents for glioma Visit the Chow Lab
Biography
Lionel Chow, MD, PhD, received his medical and graduate degrees from McGill University in Montreal, Canada, where his research focused on the regulation of T-lymphocyte signaling by the intracellular tyrosine protein kinases Lck and Csk. Following his clinical training in Pediatrics and Pediatric Hematology / Oncology at the Hospital for Sick Children in Toronto, Canada, he moved to St. Jude Children’s Research Hospital in Memphis, Tennessee to pursue his research interests. Dr. Chow's research interests have been centered on glioblastoma multiforme, a particularly devastating form of cancer in adults and children. His work has resulted in the development of a number of novel and robust laboratory models for this disease. Using these models and interfacing with clinical trials in the Neuro-Oncology Program as well as those from national consortia such as the Children's Oncology Group (COG) and the Pediatric Brain Tumor Consortium (PBTC), Dr. Chow’s laboratory will continue research in this area with the goals of better understanding the origins of this form of cancer and improving patient outcomes.
Education and Training
PhD: McGill University, Montreal, Quebec, Canada, 1996.
MDCM: McGill University, Montreal, Quebec, Canada, 1997.
Residency: The Hospital for Sick Children, University of Toronto, Toronto, Canada, 1997-2000.
Clinical Fellowship: The Hospital for Sick Children, University of Toronto, Toronto, Canada, 2000-2003.
Postdoctoral Fellowship: St. Jude Children’s Research Hospital, Memphis, TN, 2003-2009.
Clinical Fellowship: St. Jude Children’s Research Hospital, Memphis TN, 2008-2009.
Certification: Pediatrics, 2000.
Publications
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Chow LML, Endersby R, Zhu X, Rankin S, Qu C, Zhang J, Broniscer A, Ellison DW, Baker SJ. Cooperativity within and among Pten, p53 and Rb pathways induces high-grade astrocytoma in adult brain. Cancer Cell. 2011;19:305-316.
Lavado A, Lagutin O, Chow LML, Baker SJ, Oliver G. Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS Biol. 2010;8:e1000460. Cicero SA, Johnson D, Reyntjens S, Frase S, Connell S, Chow LML, Baker SJ, Sorrentino BP, Dyer MA. Cells previously identified as retinal stem cells are pigmented ciliary epithelial cells. Proc Natl Acad Sci U S A. 2009 Apr;106(16):6685-90.
Weber T, Corbett MK, Chow LML, Valentine MB, Baker SJ, Zuo J. Rapid cell-cycle reentry and cell death after acute inactivation of the retinoblastoma gene product in postnatal cochlear hair cells. Proc Natl Acad Sci U S A. 2008;105(2):781-5.
Chow LML, Zhang J, Baker SJ. Inducible Cre recombinase activity in mouse mature astrocytes and adult neural precursor cells. Transgenic Res. 2008;17(5):919-28. Chow LM, Nathan PC, Hodgson DC, Jenkin D, Weitzman S, Grant RM, Manson D, Bross A, Doyle JJ, Danjoux C, Greenberg ML. Survival and late effects in children with Hodgkin’s lymphoma treated with MOPP/ABV and low-dose, extended-field irradiation. J Clin Oncol. 2006;24:5735-5741
Chow LM, Tian Y, Weber T, Corbett M, Zuo J, Baker SJ. Inducible Cre recombinase activity in mouse cerebellar granule cell precursors and inner ear hair cells. Dev Dyn. 2006;235:2991-2998. Chow LML, Baker SJ. PTEN function in normal and neoplastic growth. Cancer Lett. 2006;241:184-196.
Grants
2011 – 2014 St. Baldrick’s Foundation Scholars Award
"Molecular targeting of pediatric high-grade glioma" 2011 – 2013 Bear Necessities Pediatric Cancer Foundation
"Micro-RNA expression in pediatric high-grade glioma" 2011 – 2013 The Childhood Brain Tumor Foundation
"Micro-RNA expression in pediatric high-grade glioma" 2011 – 2015 Sontag Foundation Distinguished Scientist Award
"Molecular targeting of high-grade astrocytoma"
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Biplab Dasgupta, PhD, MS
focuses on the integration of metabolic and signaling pathways in neural cells including neural and brain cancer stem cells. He is particularly interested in understanding the link between cellular energy sensing pathways with cellular signaling circuits that are controlled by growth factors and their receptors. Mouse models are used to understand the development of high grade human and mouse brain tumor (glioma). Visit the Dasgupta Lab.
513-803-1370
biplab.dasgupta@cchmc.org
Biplab Dasgupta, PhD, MS
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Biography
Biplab Dasgupta, PhD, MS, completed his doctorate in Molecular Biology and Immunology at the Indian Institute of Chemical Biology, Calcutta, and a postdoctoral fellowship at Washington University School of Medicine, Saint Louis. Dr. Dasgupta came to Cincinnati Children's Hospital Medical Center in August 2009 as an Assistant Professor of Pediatrics. He is interested in understanding how neural cell / stem cell metabolic and energy status is linked to cell cycle, lineage commitment, differentiation and tumorigenesis. His other interests include genetic, developmental, post-translational, tissue- and stimuli–specific regulation of the subunits that constitute the AMP kinase complex.
Education and Training
PhD: Indian Institute of Chemical Biology, Calcutta, 2003
Postdoctoral Fellowship: Washington University School of Medicine, Saint Louis
Publications
View PubMed Publications
Dasgupta B, Milbrandt J. AMP-activated protein kinase phosphorylates retinoblastoma protein to control mammalian brain development. Dev Cell. 2009 Feb;16(2):256-70. Dasgupta B, Milbrandt J. Resveratrol stimulates AMP kinase activity in neurons. Proc Natl Acad Sci U S A. 2007 Apr;24;104(17):7217-22. Revollo JR, Körner A, Mills KF, Satoh A, Wang T, Garten A, Dasgupta B, Sasaki Y, Wolberger C, Townsend RR, Milbrandt J, Kiess W, Imai S. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab. 2007 Nov;6(5):363-75. Hegedus B, Dasgupta B, Shin JE, Emnett RJ, Hart-Mahon EK, Elghazi L, Bernal-Mizrachi E, Gutmann DH. Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell. 2007 Oct 11;1(4):443-57. Warrington NM, Woerner BM, Daginakatte GC, Dasgupta B, Perry A, Gutmann DH, Rubin JB. Spatiotemporal differences in CXCL12 expression and cyclic AMP underlie the unique pattern of optic glioma growth in neurofibromatosis type 1. Cancer Res. 2007 Sep 15;67(18):8588-95. Dasgupta B, Gutmann DH. Neurofibromin regulates neural stem cell proliferation, survival, and astroglial differentiation in vitro and in vivo. J Neurosci. 2005 Jun 8;25(23):5584-94. Dasgupta B, Yi Y, Chen DY, Weber JD, Gutmann DH. Proteomic analysis reveals hyperactivation of the mammalian target of rapamycin pathway in neurofibromatosis 1-associated human and mouse brain tumors. Cancer Res. 2005 Apr 1;65(7):2755-60. Dasgupta B, Yi Y, Hegedus B, Weber JD, Gutmann DH. Cerebrospinal fluid proteomic analysis reveals dysregulation of methionine aminopeptidase-2 expression in human and mouse neurofibromatosis 1-associated glioma. Cancer Res. 2005 Nov 1;65(21):9843-50.
Dasgupta B, Li W, Perry A, Gutmann DH. Glioma formation in neurofibromatosis 1 reflects preferential activation of K-RAS in astrocytes. Cancer Res. 2005 Jan 1;65(1):236-45.
Dasgupta B, Dugan LL, Gutmann DH. The neurofibromatosis 1 gene product neurofibromin regulates pituitary adenylate cyclase-activating polypeptide-mediated signaling in astrocytes. J Neurosci. 2003 Oct 1;23(26):8949-54.
Dasgupta B, Roychoudhury K, Ganguly S, Akbar MA, Das P, Roy S. Infection of human mononuclear phagocytes and macrophage-like THP1 cells with Leishmania donovani results in modulation of expression of a subset of chemokines and a chemokine receptor. Scand J Immunol. 2003 Apr;57(4):366-74.
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Jay L. Degen, PhD
studies the mechanisms by which circulating and cell-associated hemostatic factors contribute to development, tissue reorganization, inflammatory processes and disease. He also focuses on defining the regulatory pathways by which thrombin and thrombin targets contribute to cancer biology, inflammatory joint disease, neuroinflammatory disease, bacterial virulence/host defense, and immunological disorders.
513-636-4679
jay.degen@cchmc.org
Jay L. Degen, PhD
Academic Information
Professor, UC Department of Pediatrics
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Specialties
Molecular genetics of plasminogen activation in development, hemostasis, and tumor progression; molecular genetics and biological role of plasminogen activation in development, hemostasis, wound repair, and disease
Biography
Jay L. Degen, PhD, is studying the regulation and biological roles of urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA), the two mammalian enzymes that convert plasminogen to the active serine protease, plasmin. The PA/plasmin system of proteases is of particular interest because of its apparent dual function in the lysis of vascular fibrin clots (fibrinolysis) and the degradation of extracellular matrix in tissue remodeling and cell migration events. Over the last few years, Dr. Degen's lab has generated and characterized gene-targeted mouse lines with deficits in the factors that are the foundation of the coagulation and fibrinolytic cascades, including fibrinogen-, plasminogen-, plasminogen activator-, and plasminogen activator receptor-deficient mouse lines. These unique experimental animals are being intensively analyzed with regard to a wide range of phenotypic properties, including hemostasis, wound healing, angiogenesis and tumor biology.
Education and Training
PhD: University of Washington, 1983.
Publications
View PubMed Publications
Palumbo JS, Degen JL. Mechanisms coupling the hemostatic system to colitis-associated cancer. Thromb Res. 2010 Apr;125 Suppl 2:S39-43.
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.
Mullins ES, Kombrinck KW, Talmage KE, Shaw MA, Witte DP, Ullman JM, Degen SJ, Sun W, Flick MJ, Degen JL. Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain. Blood. 2009 Jan 15;113(3):696-704.
Adhami F, Yu D, Yin W, Schloemer A, Burns KA, Liao G, Degen JL, Chen J, Kuan CY. Deleterious effects of plasminogen activators in neonatal cerebral hypoxia-ischemia. Am J Pathol. 2008 Jun;172(6):1704-16.
Palumbo JS, Barney KA, Blevins EA, Shaw MA, Mishra A, Flick MJ, Kombrinck KW, Talmage KE, Souri M, Ichinose A, Degen JL. Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. J Thromb Haemost. 2008 May;6(5):812-9.
Palumbo JS, Degen JL. Mechanisms linking tumor cell-associated procoagulant function to tumor metastasis. Thromb Res. 2007;120 Suppl 2:S22-8.
Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 2007 Nov;117(11):3224-35.
Roszell NJ, Danton MJ, Jiang M, Witte D, Daugherty C, Grimes T, Girdler B, Anderson KP, Franco RS, Degen JL, Joiner CH. Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice. Am J Hematol. 2007 Dec;82(12):1044-8.
Degen JL, Bugge TH, Goguen JD. Fibrin and fibrinolysis in infection and host defense. J Thromb Haemost. 2007 Jul;5 Suppl 1:24-31. Review.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Hu Z, Barney KA, Degen JL. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood. 2007 Jul 1;110(1):133-41.
Grants
Hemostatic factors as determinants of bacterial virulence and host defense. Principal Investigator. National Heart, Lung and Blood Institute. Sep 2006 – Aug 2011. #R01 HL085357. Thrombin-mediated proteolysis in neuroinflammatory disease. Principal Investigator. National Heart, Lung and Blood Institute. Jul 2009 – Jun 2014. #R01 HL096126.
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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
Marie-Dominique Filippi, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
I am 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 my post-doc in the laboratory of Dr David Williams, we 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, we 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, we 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.
My 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.
Education and Training
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.
Publications
View PubMed Publications
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.
Grants
Regulation of Hematopoietic Stem Cell Self Renewal. Principal Investigator. National Institutes of Health. Aug 2010 - Aug 2012. #R21 HL 104458.
Regulation of Neutrophil Migration and Polarity. National Institutes of Health. Mar 2010 - Mar 2015. #R01 HL 090676.
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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
Matthew J. Flick, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Hemostatic factors and arthritis pathogenesis
Biography
Research Interests and Focus: 1. Activation of the coagulation system, including the central coagulation protease thrombin, is a prominent feature of both human rheumatoid arthritis and experimental inflammatory arthritis. The long-term goal of Dr. Flick's research program is to determine how thrombin drives inflammatory joint disease. The proposed work will fill significant gaps in the understanding of the interplay between the thrombin- fibrinogen axis and arthritic disease, and may provide the proof-of-principle for the use of novel "customized" thrombin mutants with selected substrate specificity to treat arthritis. 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 his 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 NAFLD, but any contribution to disease progression has remained largely undefined. Using a murine model of high fat diet (HFD)-induced NAFLD, they are testing the hypothesis that thrombin activity and fibrin deposition drive local inflammatory events promoting the progression of steatosis and steatohepatitis. 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 NAFLD pathogenesis by controlling local inflammatory processes that drive steatosis and by an unanticipated and unknown mechanism tying fibrin(ogen) to HFD-induced weight gain/obesity. Their research has far-reaching implications not only for the treatment and prevention of fatty liver disease, but also for all the downstream sequelae of obesity and even the development of diet-mediated weight gain itself.
Education and Training
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.
Publications
View PubMed Publications
Flick MJ, Du X, Prasad JM, Raghu H, Palumbo JS, Smeds E, Höök M, Degen JL. Genetic elimination of the binding motif on fibrinogen for the S. aureus virulence factor ClfA improves host survival in septicemia. Blood. 2013 Jan 8. Sullivan BP, Kassel KM, Jone A, Flick MJ, Luyendyk JP. Fibrin(ogen)-independent role of plasminogen activators in acetaminophen-induced liver injury. American Journal of Pathology. 2012;180(6):2321-2329. Qi X, Flick MJ, Frederick M, Chu Z, Mason R, DeLay M, Thornton S. Saposin C Coupled Lipid Nanovesicles Specifically Target Arthritic Mouse Joints for Optical Imaging of Disease Severity. PLoSOne. 2012;7(3):e33966. Vidal B, Ardite E, Suelves M, Ruiz-Bonilla V, Janué A, Flick MJ, Degen JL, Serrano AL, Muñoz-Cánoves P. Amelioration of Duchenne muscular dystrophy in mdx mice by elimination of matrix-associated fibrin-driven inflammation coupled to the αMβ2 leukocyte integrin receptor. Human Molecular Genetics. 2012;21(9):1989-2004. Horowitz NA, Blevins EA, Miller WM, Perry AR, Talmage KE, Mullins ES, Flick MJ, Queiroz KC, Shi K, Spek CA, Conway EM, Monia BP, Weiler H, Degen JL, Palumbo JS. Thrombomodulin is a determinant of metastasis through a mechanism linked to the thrombin binding domain but not the lectin-like domain. Blood. 2011 Jul 25. Raghu H, Flick MJ. Targeting the Coagulation Factor Fibrinogen for Arthritis Therapy. Curr Pharm Biotechnol. 2011 Mar 14. Flick MJ, Chauhan AK, Frederick M, Talmage KE, Kombrinck KW, Miller W, Mullins ES, Palumbo JS, Zheng X, Esmon NL, Esmon CT, Thornton S, Becker A, Pelc LA, Di Cera E, Wagner DD, Degen JL. The development of inflammatory joint disease is attenuated in mice expressing the anticoagulant prothrombin mutant W215A/E217A. Blood. 2011 Jun 9;117(23):6326-37. Steinbrecher KA, Horowitz NA, Blevins EA, Barney KA, Shaw MA, Harmel-Laws E, Finkelman FD, Flick MJ, Pinkerton MD, Talmage KE, Kombrinck KW, Witte DP, Palumbo JS. Colitis-associated cancer is dependent on the interplay between the hemostatic and inflammatory systems and supported by integrin alpha(M)beta(2) engagement of fibrinogen. Cancer Res. 2010 Apr 1;70(7):2634-43. 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. Mullins ES, Kombrinck KW, Talmage KE, Shaw MA, Witte DP, Ullman JM, Degen SJ, Sun W, Flick MJ, Degen JL. Genetic elimination of prothrombin in adult mice is not compatible with survival and results in spontaneous hemorrhagic events in both heart and brain. Blood. 2009 Jan 15;113(3):696-704.
Grants
Mechanisms linking the hemostatic protease thrombin to arthritic disease. Principal Investigator. National Institute of Arthritis and Musculoskeletal and Skin Diseases. Jul 2009 - Jun 2014. #R01 AR056990. Thrombin-mediated proteolysis in neuroinflammatory disease. Co-investigator. National Heart, Lung, and Blood Institute. Jul 2009 - Jun 2014. #R01 HL096126. Coagulation factors and the pathogenesis of non-alcoholic fatty liver disease. Principle Investigator. Cincinnati Children’s Hospital Digestive Health Center (DHC) Pilot and Feasibility Grant. Jun 2012 - May 2013. P30 DK078392. 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. Analysis of Staphylococcus Host Interactions. Co-investigator. NIH. Sep 2010 - Aug 2015. R01 AI020662.
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Hartmut Geiger, PhD
Director, Mouse Core
focuses on hematopoietic stem cells and their process of hematopoiesis. Blood cells are responsible for constant oxygen supply, broad and specialized immune protection, wound healing, and much more of which we might not be aware. Visit the Geiger Lab.
513-636-1338
hartmut.geiger@cchmc.org
Hartmut Geiger, PhD
Director, Mouse Core
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Hematopoietic stem cells; genetics; aging/longevity; plasticity of stem cells; mobilization; DNA-repair Visit the Geiger Lab.
Education and Training
MS: Studies in chemistry at the University Karlsruhe, Germany and studies in biochemistry at the University Witten/Herdecke, Germany (1996).
PhD: Max-Planck Institut für Immunbiologie in Freiburg, Germany.
Plasticity of murine hematopoietic stem cells (1999).
Postdoctoral Studies: University of Kentucky, Lexington, USA.
Genetic analysis of hematopoiesis and aging/longevity in mice.
Publications
View PubMed Publications
Ryan MA, Nattamai KJ, Xing E, Schleimer D, Daria D, Sengupta A, Köhler A, Liu W, Gunzer M, Jansen M, Ratner N, Le Cras TD, Waterstrat A, Van Zant G, Cancelas JA, Zheng Y, Geiger H. Pharmacological inhibition of EGFR signaling enhances G-CSF-induced hematopoietic stem cell mobilization. Nat Med. 2010 Oct;16(10):1141-6. 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. 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. Geiger H, Rudolph KL. Aging in the lymphohematopoietic stem cell compartment. Trends Immunol. 2009 Jul;30(7):360-5. Epub 2009 Jun 18. Review. Geiger H, David S, Nattamai KJ, Jan V. Quantification of genomic mutations in murine hematopoietic cells. Methods Mol Biol. 2009;506:423-36. 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. Bhatla D, Gerbing RB, Alonzo TA, Conner H, Ross JA, Meshinchi S, Zhai X, Zamzow T, Mehta PA, Geiger H, Perentesis J, Davies SM. Cytidine deaminase genotype and toxicity of cytosine arabinoside therapy in children with acute myeloid leukemia. Br J Haematol. 2009 Feb;144(3):388-94. Milsom MD, Jerabek-Willemsen M, Harris CE, Schambach A, Broun E, Bailey J, Jansen M, Schleimer D, Nattamai K, Wilhelm J, Watson A, Geiger H, Margison GP, Moritz T, Baum C, Thomale J, Williams DA. Reciprocal relationship between O6-methylguanine-DNA methyltransferase P140K expression level and chemoprotection of hematopoietic stem cells. Cancer Res. 2008 Aug 1;68(15):6171-80. Diwan A, Koesters AG, Capella D, Geiger H, Kalfa TA, Dorn GW 2nd. Targeting erythroblast-specific apoptosis in experimental anemia. Apoptosis. 2008 Aug;13(8):1022-30. 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
Activated Protein C for Treatment of Radiation Combined Injury. Principal Investigator. National Institutes of Health. Sep 2010 - Sep 2013. #R33 AI 080557.
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Elke Grassman, PhD
Director, Translational Trials Development and Support Laboratory
focuses on phase I gene transfer/cell therapy trials, investigational new drug (IND) submissions to the FDA, the evaluation of new vectors with respect to safety and efficacy, development of tailored assays for trial monitoring, and a stat Endotoxin testing service to support cell therapy trials.
513-636-0958
elke.grassman@cchmc.org
Elke Grassman, PhD
Director, Translational Trials Development and Support Laboratory
Academic Information
UC Department of Pediatrics
Field Service Assistant Professor
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Specialties
Clinical InterestsDiagnostic assay for the identification of complementation groups on specimens from patients diagnosed with Fanconi Anemia Research InterestsPhase I gene transfer / cell therapy trials; investigational new drug (IND) submissions to the FDA; evaluate new vectors with respect to safety and efficacy; develop tailored assays for trial monitoring; stat Endotoxin testing service to support cell therapy trials
Education and Training
MS: University of Würzburg, Würzburg, Germany, 1995.
PhD: University of Göttingen, Göttingen, Germany, 1999.
Publications
View PubMed Publications
Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood. 2009 Jul 2;114(1):174-80. Epub 2009 May 7. Balcik B, Grassman E, Reeves L. Database setup for preclinical studies of gene-modified hematopoiesis. Methods Mol Biol. 2009;506:467-76. Schuesler T, Reeves L, Kalle C, Grassman E. Copy number determination of genetically-modified hematopoietic stem cells. Methods Mol Biol. 2009;506:281-98.
Will E, Bailey J, Schuesler T, Modlich U, Balcik B, Burzynski B, Witte D, Layh-Schmitt G, Rudolph C, Schlegelberger B, Von Kalle C, Baum C, Sorrentino BP, Wagner LM, Kelly P, Reeves L, Williams DA. Importance of murine study design for testing toxicity of retroviral vectors in support of Phase I trials. Mol. Ther. 2007 Apr 15(4):782-91. Li Z, Kustikova OS, Kamino K, Neumann T, Rhein M, Grassman E, Fehse B, Baum C. Mutagenesis by Replication-Deficient Retroviral Vectors Encoding the Large T Oncogene. Annals of the New York Academy of Sciences. 2007 1106:95-113. Thornhill SI, Schambach A, Howe SJ, Ulaganathan M, Grassman E, Williams D, Schiedlmeier B, Sebire NJ, Gaspar HB, Kinnon C, Baum C, Thrasher AJ. Self-inactivating gammaretroviral vectors for gene therapy of X-linked severe combined immunodeficiency. Mol Ther. 2008 16(3):590-8. Zychlinski D, Schambach A, Modlich U, Maetzig T, Meyer J, Grassman E, Mishra A, Baum C. Physiological promoters reduce the genotoxic risk of integrating gene vectors. Mol Ther. 2008 16(4):718-25.
Grants
Proposed study of Retrovirus Vector-Mediated Insertional. Principal Investigator. National Institutes of Health. Mar 2011 - Mar 2013.
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H. Leighton Grimes, PhD
Director, Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology
focuses his research on the genetic development of cancerous cells and inherited blood diseases. His lab utilizes the Growth factor independent-1 transcription factor as a molecular probe to dissect hematopoiesis and leukemia. Dr. Grimes serves as the director of the Cancer Pathology Program of the Divisions of Experimental Hematology and Pathology. Visit the Grimes Lab.
513-636-6089
lee.grimes@cchmc.org
H. Leighton Grimes, PhD
Director, Cancer Pathology Program of the Division of Experimental Hematology and the Division of Pathology
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Biography
Grimes Laboratory: The cloning and characterization of oncoproteins and tumor suppressors over the last 25 years has not only resulted in a greater understanding of the molecular mechanisms of transformation, but it has also provided a large set of therapeutic targets. Our lab is interested in the progression of a cell with a single genetic lesion to an invasive cancer with multiple genetic alterations. We focus on the Growth factor independence-1 (Gfi1) transcription factor, which is poorly oncogenic alone, but which potently collaborates with well known oncoproteins such as c-MYC. Gfi1 is the most frequently targeted gene in Moloney murine leukemia virus-induced tumors and induces tumor progression to cytokine-independent growth. In contrast, loss of Gfi1 in hematopoietic stem cells induces cell cycle progression and eventual bone marrow failure; implicating Gfi1 as a tumor suppressor in such cells. Gfi1 null mice have no mature neutrophils, and we have identified humans with Severe Congenital Neutropenia (SCN) and Non-Immune Chronic Idiopathic Neutropenia of Adults (NI-CINA) bearing mutations in Gfi1. Interestingly, such patients are at increased risk for the development of myelodysplastic syndromes and acute myeloid leukemia. We have recently generated the first mouse model of Severe Congenital Neutropenia through the expression of mutant Gfi1 proteins in primary murine hematopoietic cells. Moreover, we are utilizing mouse models of human cancer to assess the risk of Gfi1 mutant humans for the development of acute myeloid leukemia.
Education and Training
PhD: Immunology and Molecular Pathology, University of Florida, Gainesville, FL.
Postdoctoral Fellow: Fox Chase Cancer Center.
Publications
View PubMed Publications
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. 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. Meyer SE, Hasenstein JR, Baktula A, Velu CS, Xu Y, Wan H, Whitsett JA, Gilks CB, Grimes HL. Kruppel-like factor 5 is not required for K-RasG12D lung tumorigenesis, but represses ABCG2 expression and is associated with better disease-specific survival. Am J Pathol. 2010 Sep;177(3):1503-13. Phelan JD, Shroyer NF, Cook T, Gebelein B, Grimes HL. Gfi1-cells and circuits: unraveling transcriptional networks of development and disease. Curr Opin Hematol. 2010 Jul;17(4):300-7. Review. 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. Guo F, Velu CS, Grimes HL, Zheng Y. Rho GTPase Cdc42 is essential for B-lymphocyte development and activation. Blood. 2009 Oct 1;114(14):2909-16. Horman SR, Velu CS, Chaubey A, Bourdeau T, Zhu J, Paul WE, Gebelein B, Grimes HL. Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood. 2009 May 28;113(22):5466-75. Velu CS, Baktula AM, Grimes HL. Gfi1 regulates miR-21 and miR-196b to control myelopoiesis. Blood. 2009 May 7;113(19):4720-8. 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. Li-Kroeger D, Witt LM, Grimes HL, Cook TA, Gebelein B. Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Dev Cell. 2008 Aug;15(2):298-308.
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Fukun Guo, PhD
Assistant Professor - Division of Experimental Hematology and Cancer Biology
studies Rho GTPases and T and B lymphocyte development and function.
513-803-1118
fukun.guo@cchmc.org
Fukun Guo, PhD
Assistant Professor - Division of Experimental Hematology and Cancer Biology
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Rho GTPases and T and B lymphocyte development and function
Education and Training
BS: Jilin University, Changchun, Jilin, China,1994.
MS: Academy of Military Medical Sciences, Beijing, China, 1997.
PhD: Southern Medical University, Guangzhou, Guangdong, China, 2000.
Postdoctoral Research Associate: University of Tennessee, Memphis, TN, 2000-2002; Children’s Hospital Medical Center, Cincinnati, OH, 2002-2004.
Research Associate: Southern Medical University, Guangzhou, Guangdong, China, 2000. Children’s Hospital Medical Center, Cincinnati, OH, 2004.
Research Instructor: Children’s Hospital Medical Center, Cincinnati, OH. 2005-2009
Publications
View PubMed Publications
Sachin Kumar, Juying Xu, Charles Perkins, Fukun Guo, Scott Snapper, Fred D Finkelman, Yi Zheng, Marie-Dominique Filippi. Cdc42 regulates neutrophil migration via crosstalk between WASp, CD11b, and microtubules. Blood. 2012;120(17):3563-3574. Juan Li, Nuyun Liu, Kangrong Lu, Lei Zhang, Jingjing Gu, Fukun Guo, Shengli An, Lin Zhang, Lu Zhang. Cocaine-induced dendritic remodeling occurs in both D1 and D2 dopamine receptor-expressing neurons in the nucleus accumbens. Neuroscience Letters. 2012;517(2):118-122. Shuangmin Zhang, Xuan Zhou, Richard A Lang, Fukun Guo*. RhoA of the Rho family small GTPases is essential for B lymphocyte development. PLoS One. 2012.7(3):e33773 (*corresponding author). Jessica G Woo, M Lourdes Guerrero, Fukun Guo, J Martin, Barbara S Davidson, Hilda Ortega, Guillermo M Ruiz-Palacios, Ardythe L Morrow. Human Milk Adiponectin Impacts Infant Weight Trajectory During The Second Year Of Life. Journal of Pediatric Gastroenterology & Nutrition. 2012;54(4):532-539. Guo F, Cancelas JA, Hildeman D, Williams DA, Zheng Y. Rac GTPase isoforms, Rac1 and Rac2, play a redundant and crucial role in T-cell development. Blood, 2008, 112 (5):1767. Guo F, Zhang S, Tripathi P, Mattner J, Phelan J, Sproles A, Mo J, Wills-Karp M, Grimes HL, Hildeman D, Zheng Y. Distinct roles of Cdc42 in thymopoiesis and effector and memory T cell differentiation. PLoS One, 2011, 6(3):e18002. Shang X, Cancelas JA, Li L, Guo F, Liu W, Johnson JF, Ficker A, Daria D, Geiger H, Ratner N, Zheng Y. R-Ras and Rac GTPase crosstalk regulates hematopoietic progenitor cell migration, homing and mobilization. Journal of Biological Chemistry, 2011, 286(27):24068. Sipes NS, Feng Y, Guo F, Lee HO, Chou FS, Cheng J, Mulloy J, Zheng Y. Cdc42 regulates extracellular matrix remodeling in three dimensions. Journal of Biological Chemistry, 2011, 286(42):36469-77. 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. Bosco EE, Ni W, Wang L, Guo F, Johnson JF, Zheng Y. Rac1 targeting suppresses p53 deficiency-mediated lymphomagenesis. Blood. 2010 Apr 22;115(16):3320-8.
Grants
Physiological Role of Cdc42 in T Cell Polarity. Principal Investigator. Trustee Grant, Cincinnati Children’s Hospital Medical Center. 2009 - 2011.
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Gang Huang, PhD
focuses on genetic and epigenetic regulations of normal blood cell development and leukemia. His team demonstrated that AML1/CBFβ and Mixed-Lineage Leukemia (MLL) protein form a regulatory complex, which is important for normal blood development and acts as a tumor suppressor in leukemia.
513-636-3214
gang.huang@cchmc.org
Gang Huang, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Research in Dr. Huang’s laboratory focuses on genetic and epigenetic regulations of blood cell normal development and leukemia. We first demonstrated that AML1/CBFβ (a hetero-dimer transcription factor) and Mixed-Lineage Leukemia (MLL) protein (an enzyme which methylates lysine 4 of histone H3 tails), form a regulatory complex, which is important for normal blood development and acts as a tumor suppressor in leukemia. Mutations in either one of these three genes account for majority of acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes (MDS).
We also found that the AML1/CBFβ/MLL complex regulates another transcription factor, PU.1, through the upstream regulatory region of the PU.1 gene and that the epigenetic changes of the histone tails occurring in the PU.1 regulatory region correlate with the PU.1 expression level. PU.1 expression level changes are critical for blood cell differentiation and dysregulation of PU.1 dosages leading to leukemia.
This research will provide new insight into the interplay between genetics and epigenetics in normal blood development and leukemia. It will also help to develop generic drugs for most of the AML, ALL and MDS, which will benefit the future clinical treatments.
Education and Training
BS: Peking University, College of Science, Beijing, P.R. China, 1991.
MS: Inner Mongolia University, Graduate School of Science, Huhhort, P.R. China, 1994.
PhD: Kyoto University, Graduate School of Medicine, Kyoto, Japan, 2001.
Publications
Viwe PubMed Publications
Staber PB, Zhang P, Ye M, Welner R, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jorda M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Orkin S, Gottgens B, Rosenbauer F, Huang G, Tenen DG. Sustained PU.1 Levels Balance Cell Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells. Mol Cell. 2013. Hirai H, Kamio N, Huang G, Matsusue A, Ogino S, Kimura N, Satake S, Ashihara E, Imanishi J, Tenen MD, DG, Maekawa T. Cyclic AMP Responsive Element Binding proteins are involved in “emergency” granulopoiesis through the upregulation of CCAAT/Enhancer Binder Protein. PlosONE. 2013 Zhang Y, Chen A, Yan XM, Huang G. Disordered epigenetic regulation in MLL-related leukemia. Int J Hematol. 2012 Oct;96(4):428-37. Zhang Y, Yan XM, Sashida G, Zhao XH, Rao YL, Goyama S, Whitman SP, Zorko N, Bernot K, Conway R, Witte D, Wang QF, Tenen DG, Xiao ZJ, Marcucci G, Mulloy J, Grimes HL, Caligiuri MA, Huang G. Mll partial tandem duplication (Mll-PTD) causes abnormal hematopoiesis in mice by reprogramming, enhancing self-renewal, lineage skewing and blocking myeloid differentiation. Blood. 2012 Aug 2;120(5):1118-29. Zorko N, Bernot KS, Whitman SP, Siebenaler RF, Ahmed E, Marcucci GG, Yanes DA, McConnell KK, Mao C. Kalu C, Zhang XL, Jarjoura D, Dorrance AM, Lee BH, Huang G, Marcucci G, Caligiuri MA. Mll Partial Tandem Duplication and Flt3-Internal Tandem Duplication in a Double Knock-in Mouse Recapitulates Features of Counterpart Human Acute Myeloid Leukemias. Blood. 2012 Aug 2;120(5):1130-6. Huang G, Zhao XH, Wang L, Elf S, Xu H, Zhao XY, Sashida G, Zhang Y, Liu Y, Lee J, Menendez S, Yang YY, Yan XM, Zhang P, Tenen DG, Osato M, Hsieh JDJ, Nimer SD. The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood. 2011;118(25):6544-52. Wang L, Gural A, Sun XJ, Zhao X, Perna F, Huang G, Hatlen MA, Vu L, Liu F, Xu H, Asai T, Xu H, Deblasio T, Menendez S, Voza F, Jiang Y, Cole PA, Zhang J, Melnick A, Roeder RG, Nimer SD. The leukemogenicity of AML1-ETO is dependent on site-specific lysine Acetylation. Science. 2011;333(6043):765-9. Huang G, Zhang P, Hirai H, Elf S, Yan XM, Chen Z, Koschmieder S, Okuno Y, Dayaram T, Growney JD, Shivdasani RA, Gilliland DG, Speck NA, Nimer SD, Tenen DG. PU.1 is a major downstream target of AML1/RUNX1 in adult hematopoiesis. Nat Genet. 2008;40:51-60.
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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
Theodosia A. Kalfa, MD, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Signaling in erythrocytes; erythropoiesis; Sickle Cell disease; reactive oxygen species Visit the Kalfa Lab.
Education and Training
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.
Publications
View PubMed Publications
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. Epub ahead of print. 2013. 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
Genetic Manipulation of Red Cell Volume Regulation. National Heart, Lung, and Blood Institute. Apr 2008 - Mar 2013. #U54 HL070871. Rho GTPases in Terminal Erythroid Maturation. Principal Investigator. NIH/NHLBI. Sep 2012 - Jun 2016. #1R01HL116352. TCD with Transfusions Changing to Hydroxyurea. Co-investigator. NIH/Baylor. Aug 2009 - Jul 2014. #R01HL095647.
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Kakajan Komurov, PhD
focuses on computational systems biology. His specific research interests include: 1) the development of novel computational methodology and software for efficient network-based data analyses and 2) computational analyses of dynamic organizational principles in intracellular molecular networks and their specific alterations that contribute to disease phenotypes. Visit the Komurov Lab.
513-803-5122
kakajan.komurov@cchmc.org
Kakajan Komurov, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Education and Training
PhD: The University of Texas Southwestern Medical Center, Dallas TX.
Publications
Komurov K, Ram PT. Patterns of human gene expression variance show strong associations with signaling network hierarchy. BMC Syst Biol. 2010 Nov 12;4:154.
Komurov K, White MA, Ram PT. Use of data-biased random walks on graphs for the retrieval of context-specific networks from genomic data. PLoS Comput Biol. 2010 Aug 19;6(8).
Taube JH*, Herschkowitz JI*, Komurov K*, Zhou AY, Gupta S, Yang J, Hartwell K, Onder TT, Gupta PB, Evans KW, Hollier BG, Ram PT, Lander ES, Rosen JM, Weinberg RA, Mani SA. Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc Natl Acad Sci U S A. 2010 Aug 31;107(35):15449-54. (*Co-first author) Komurov K, Padron D, Cheng T, Roth M, Rosenblatt KP, White MA. Comprehensive mapping of the human kinome to epidermal growth factor receptor signaling. J Biol Chem. 2010 Jul 2;285(27):21134-42.
Komurov K, Gunes MH, White MA. Fine-scale dissection of functional protein network organization by statistical network analysis. PLoS One. 2009 Jun 24;4(6):e6017.
Komurov K, White M. Revealing static and dynamic modular architecture of the eukaryotic protein interaction network. Mol Syst Biol. 2007;3:110.
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Ashish R. Kumar, MD, PhD
is a Pediatric Hematologist-Oncologist who has a research program investigating the biology of leukemia caused by MLL-fusion genes. These leukemias are most common in infants and frequently fatal. The research in Dr. Kumar's lab is focused at identifying downstream targets of MLL-fusion proteins that could be exploited to develop novel therapies. Currently, the Kumar lab is investigating the role of MEIS1 in MLL-leukemia. Visit the Kumar Lab.
513-803-1631
ashish.kumar@cchmc.org
Ashish R. Kumar, MD, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsChildhood cancer and blood disorders; immune deficiency Research InterestsLeukemia biology; cancer biology Visit the Kumar Lab.
Biography
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. As a faculty of the Masonic Cancer Center, he was also part of the Genetic Mechanisms of Cancer research program. 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.
Education and Training
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.
Publications
View PubMed Publications
Kumar AR, Yao Q, Li Q, Sam TA, Kersey JH. t(4;11) leukemias display addiction to MLL-AF4 but not to AF4-MLL. Leuk Res. 2011 Mar;35(3):305-9. Kumar AR, Sarver AL, Wu B, Kersey JH. Meis1 maintains stemness signature in MLL-AF9 leukemia. Blood. 2010 Apr 29;115(17):3642-3. Burke MJ, Cao Q, Trotz B, Weigel B, Kumar A, Smith A, Verneris MR. Allogeneic hematopoietic cell transplantation (allogeneic HCT) for treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer. 2009 Dec 15;53(7):1289-94.
Kumar AR, Li Q, Hudson WA, Chen W, Yao Q, Sam TN, Wu B, Lund EA, Kowal BJ and Kersey JH. A role for MEIS1 in MLL-fusion gene leukemia. Blood. 2009 Feb 19; 113(8):1756-8.
Chen W*, Kumar AR*, Hudson WA, Li Q, Wu B, Staggs RA, Lund EA, Sam TN and Kersey JH. Malignant transformation initiated by Mll-AF9: Gene dosage and critical target cells. Cancer Cell. 2008 May; 13: 432-440. *Co-first authors.
Kris Ann P. Schultz, MD, Joseph P. Neglia, MD, MPH, Angela R. Smith, MD, Hans D. Ochs, MD, Dr. med., Troy R. Torgerson, MD, PhD, and Ashish Kumar, MD, PhD. Familial Hemophagocytic Lymphohistiocytosis in Two Brothers With X-Linked Agammaglobulinemia. Pediatric Blood and Cancer 2008; 51:293–295.
White JG, Kumar AR, Hogan MJ. Gray Platelet Syndrome in a Somalian Family. Platelets. 2006 Dec; 17:519-527.
Mehta PA, Davies SM, Kumar A, Devidas M, Lee S, Zamzow T, Elliott J, Villanueva J, Pullen J, Zewge Y, and Filipovich A; Children’s Oncology Group. Perforin polymorphism A91V and susceptibility to B-precursor childhood acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia. 2006 Sep; 20; 1539-1541.
Chen W, Li Q, Hudson WA, Kumar A, Kirchhof N, Kersey JH. A murine Mll-AF4 knock-in model results in lymphoid and myeloid deregulation and hematological malignancy. Blood. 2006 Jul 15; 108:669-677.
Grants
Molecular Pathogenesis of MLL-Fusion Gene Leukemia. View PubMed Publications. Principal Investigator. National Institute of Health. Jul 2007 - Jun 2012.
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Carolyn M. Lutzko, PhD
studies the regulation of human pluripotent stem cells, somatic cell reprogramming in iPSC, human embryonic stem cell physiology and differentiation, hESC, and cystic fibrosis.
513-803-3420
carolyn.lutzko@cchmc.org
Carolyn M. Lutzko, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Regulating human pluripotent stem cell; somatic cell reprogramming in iPSC; human embryonic stem cell physiology and differentiation; hESC; Cystic Fibrosis
Education and Training
BA: University of Guelph, S.Sc. Hon, Molecular Biology and Genetics Guelph, Ontario, Canada 1992.
PhD: University of Toronto, PhD Department of Laboratory Medicine Toronto, Ontario, Canada 1999.
Fellowship: Childrens Hospital Los Angeles Department of Pediatrics Division of Research Immunology/BMT Los Angeles, California 1999-2002.
Publications
View PubMed Publications
Mishra S, Wang X, Smiley N, Bui KC, Senadheera D, Chang D, Lutzko C. In utero delivery of lentiviral supernatant to the amniotic fluid genetically modifies airway epithelial progenitors. American Journal of Respiratory Cellular and Molecular Biology. 2010. Bui KC, Senadheera D, Wang X, Hendrickson B, Friedlich P, Lutzko C. Isolation of progenitors from the peripheral blood of patients with acute respiratory or cardiac failure who required ECMO support. American Journal of Respiratory and Critical Care Medicine. 2010 181:226-237. Harb R, Xie G, Lutzko C, Guo Y, Wang X, Hill CK, Kanel GC, DeLeve LD. Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury. Gastroenterology. 2009 137:704-12. Chang D, Tsai S, Wang X, Xia P, Senadheera D, Lutzko C. Molecular characterization of the human nanog protein. Stem Cells. 2009 27:812-821. Jiang X, Gwye Y, Lutzko C, Lawlor ER. Isolation and characterization of neural crest stem cells derived from in vitro – differentiated human embryonic stem cells. Stem Cells and Development. 2009 18:259-270. Melchior K, Weib J, Zaehres H, Yong-Mi K, Lutzko C, Roosta N, Hescheler J, Muschen M. The WNT receptor FZD7 contributes to self-renewal of signaling of human embryonic stem cells. Journal of Biological Chemistry. 2008 389:897-903. Liebler J, Lutzko C, Banfalvi A, Senadheera D, Crandall ED, Borok Z. Retention of human bone marrow-derived cells in murine lungs following bleomycin injury. American Journal of Pathology-Lung and Cellular Molecular Physiology. 2008 295:285-292. Rodriguez RT, Velkey JM, Lutzko C, Seerke R, Kohn DB, O’Shea KS, Firpo MT. Manipulation of OCT4 levels in human embryonic stem cells results in induction of differential cell types. Journal of Experimental Biology & Medicine. 2007 232:1368-80. Hendrickson B, Senadheera D, Mishra S, Bui KC, Wang XC, Chan B, Petersen, D, Pepper K, Lutzko C. Development of lentiviral vectors with regulated respiratory epithelia expression in vivo. American Journal of Respiratory Cellular and Molecular Biology. 2007 37:414-23.
Grants
Human Embryonic Stem Cell Facility. California Institute of Regenerative Medicine. Dec 2007-Nov 2012. CL1-00507-1.
Training Grant II. Co-Investigator. California Institute of Regenerative Medicine. Aug 2009-Jul 2012.
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Punam Malik, MD
Director, Comprehensive Sickle Cell Program
works to correct the gene responsible for sickle cell anemia. One of our lab’s major projects uses gene therapy to treat sickle cell disease. His lab is also interested in gene therapy for other diseases. He has developed various methods for delivering corrective genes to cells, improving methods for gene therapy in general.
513-636-1333
punam.malik@cchmc.org
Punam Malik, MD
Director, Comprehensive Sickle Cell Program
Program Leader, Molecular and Gene Therapy Program
Academic Information
Associate Professor, UC Department of Pediatrics
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Education and Training
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.
Publications
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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.
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Ruhikanta A. Meetei, PhD
focuses on functional analysis of Fanconi anemia gene products. The major research focus includes identification of new FA genes and signal transduction pathways that regulate DNA-damage-induced activation of the FA-core complex.
513-636-1768
ruhikanta.meetei@cchmc.org
Ruhikanta A. Meetei, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsFanconi anemia; chromosome instability; DNA repair; multiprotein complex Research InterestsResearch in my laboratory focuses on functional analysis of Fanconi anemia gene products. The major research focus includes identification of new FA genes and signal transduction pathways that regulate DNA damage induced activation of the FA-core complex. Important technologies include biochemical purification of multiprotein complexes from human cell extracts, immunoprecipitation, RNAi, and biochemical assays. My long-term research goal is to use Fanconi anemia as a model system to study some of the important fundamental questions of cancer biology in general.
Education and Training
BS: Manipur University, India, 1989.
MS: Manipur University, India, 1992.
PhD: Indian Institute of Science, Bangalore, India, 2000.
Publications
View PubMed Publications
Singh TR, Saro D, Ali AM, Zheng XF, Du CH, Killen MW, Sachpatzidis A, Wahengbam K, Pierce AJ, Xiong Y, Sung P, Meetei AR. MHF1-MHF2, a histone-fold-containing protein complex, participates in the Fanconi anemia pathway via FANCM. Mol Cell. 2010 Mar 26;37(6):879-86. Singh TR, Bakker ST, Agarwal S, Jansen M, Grassman E, Godthelp BC, Ali AM, Du CH, Rooimans MA, Fan Q, Wahengbam K, Steltenpool J, Andreassen PR, Williams DA, Joenje H, de Winter JP, Meetei AR. Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin uniquely characterize Fanconi anemia complementation group M. Blood. 2009 Jul 2;114(1):174-80. Ali AM, Kirby M, Jansen M, Lach FP, Schulte J, Singh TR, Batish SD, Auerbach AD, Williams DA, Meetei AR. Identification and characterization of mutations in FANCL gene: a second case of Fanconi anemia belonging to FA-L complementation group. Hum Mutat. 2009 Jul;30(7):E761-70. Ali AM, Singh TR, Meetei AR. FANCM-FAAP24 and FANCJ: FA proteins that metabolize DNA. Mutat Res. 2009 Jul 31;668(1-2):20-6. Epub 2009 Apr 18. Review. Singh TR, Ali AM, Busygina V, Raynard S, Fan Q, Du CH, Andreassen PR, Sung P, Meetei AR. BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev. 2008 Oct 15;22(20):2856-68. Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W. A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005 Sep;37(9):958-63.
Grants
Function and Regulation of FANCM in Fanconi Anemia. National Institutes of Health. May 2007 - Apr 2012. #R01 HL 084082.
Functional and Molecular Characterization of Two New Members of the Bloom Syndrome Complex Ohio Cancer Research Associates. Jul 2010 - Jun 2012.
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Benjamin E. Mizukawa, MD
is trained in pediatric hematology/oncology with a research emphasis in leukemia biology and novel therapeutics. His work is focused on understanding the role of small Rho GTPases in myeloid leukemia development and progression, with the translational goal of identifying new targets for drug development.
513-636-1335
benjamin.mizukawa@cchmc.org
Benjamin E. Mizukawa, MD
Academic Information
Instructor, UC Department of Pediatrics
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Specialties
Pediatric leukemia and lymphoma; investigation of the role of small Rho GTPases in leukemogenesis and leukemic stem cell biology and their potential as therapeutic targets in acute myeloid leukemia; development of xenograft models for use in testing novel therapeutics
Education and Training
MD: University of Utah, Salt Lake City, UT, 2004.
Residency: Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Fellowship: Cincinnati Children’s Hospital Medical Center, Cincinnati, OH.
Certification: Pediatrics, 2008
Pediatric Hematology/Oncology, 2011
Publications
View PubMed Publications
Wunderlich M, Mizukawa B, Chou FS, Sexton C, Shrestha M, Saunthararajah Y, Mulloy JC. AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model. Blood. Epub ahead of print. 2013. Chou FS, Griesinger A, Wunderlich M, Lin S, Link KA, Shrestha M, Goyama S, Mizukawa B, Shen S, Marcucci G, Mulloy JC. The THPO/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO. Blood. 2012;120(4):709-19. Mizukawa B, Wei J, Shrestha M, Wunderlich M, Chou FS, Griesinger A, Harris CE, Kumar AR, Zheng Y, Williams DA, Mulloy JC. Inhibition of Rac GTPase signaling and downstream pro-survival Bcl-2 proteins as combination targeted therapy in MLL-AF9 leukemia. Blood 118(19):5235-45, 2011. 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 56(5): 840-2, 2011. Wunderlich M, Chou FS, Link KA, Mizukawa B, Perry RL, Carroll M, Mulloy JC. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF, and IL-3. Leukemia, 2010; 24(10):1785-8.
Grants
Characterization of Rho GTPases in acute myeloid leukemia (AML) and their potential as therapeutic targets. Principal Investigator. Pediatric Scientist Development Program (PSDP) Fellowship. 2008 - 2011. Targeting Leukemia Cell Interaction with the Marrow Niche. Sub-Investigator. Child Health Research Career Development Award (CHRCDA) NIH K12. 2011 - 2012. Targeting Cdc42 in Leukemia Stem Cells. Principal Investigator. Procter Scholar Award. Cincinnati Children's Hospital Research Foundation. 2012 - 2013.
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James C. Mulloy, PhD
focuses on using human hematopoietic stem cells to model leukemia. His lab is expressing the fusion protein, AML1-ETO, in human CD34+ stem cells by retroviral transduction and characterizing the genetic and functional alterations that occur due to expression of this oncogene. Visit the Mulloy Lab.
513-636-1844
james.mulloy@cchmc.org
James C. Mulloy, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Education and Training
BA: St. Anselm College, Manchester, New Hampshire, 1986.
MS: Rutgers University-University of Medicine and Dentistry, New Brunswick, New Jersey, 1989.
PhD: Rutgers University-University of Medicine and Dentistry, New Brunswick, New Jersey, 1992.
Publications
View PubMed Publications
Wunderlich M, Mizukawa B, Chou FS, Sexton C, Shrestha M, Saunthararajah Y, Mulloy JC. AML cells are differentially sensitive to chemotherapy treatment in a human xenograft model. Blood. March;121:e90-e97. 2013. Bell-Horwath, T. B., Vadukoot, A. K., Li, G.; Thowfeik, S., Wunderlich, M., Mulloy, JC, Merino, E. J. Novel oxidatively activated anticancer agents selectively target acute myeloid leukemia. Bioorganic & Medicinal Chemistry Letters 23:2951–2954, 2013. Goyama S, Mulloy JC. Making healthy stem cells: the new role of TPO. Cell Stem Cell. Jan 3;12(1):8-9. 2013. Negrotto S, Ng KP, Jankowska AM, Bodo J, Gopalan B, Guinta K, Mulloy JC, Hsi E, Maciejewski J, Saunthararajah Y. CpG methylation patterns and decitabine treatment response in acute myeloid leukemia cells and normal hematopoietic precursors. Leukemia, 26(2):244-54, Feb 2012. Maiques-Diaz A, Chou FS, Wunderlich M, Gómez-López G, Jacinto FV, Rodriguez-Perales S, Larrayoz MJ, Calasanz MJ, Mulloy JC, Cigudosa JC, Alvarez S. Chromatin modifications induced by the AML1/ETO fusion protein reversibly silence its genomic targets through AML1 and Sp1 binding motifs. Leukemia, 26(6):1329-37, Jun 2012. Li Z, Huang H, Chen P, He M, Li Y, Arnovitz S, Jiang X, He C, Hyjek E, Zhang J, Zhang Z, Elkahloun A, Cao D, Shen C, Wunderlich M, Wang Y, Neilly MB, Jin J, Wei M, Lu J, Valk PJ, Delwel R, Lowenberg B, Le Beau MM, Vardiman J, Mulloy JC, Zeleznik-Le NJ, Liu PP, Zhang J, Chen J. miR-196b directly targets bothHOXA9/MEIS1 oncogenes and FAS tumour suppressor in MLL-rearranged leukaemia. Nat Commun. 2:688. doi: 10.1038/ncomms1681. Feb 21 2012. Yoshimi M, Goyama S, Kawazu M, Nakagawa M, Ichikawa M, Imai Y, Kumano K, Asai T, Mulloy JC, Kraft AS, Takahashi T, Shirafuji N, Kurokawa M. Multiple phosphorylation sites are important for RUNX1 activity in early hematopoiesis and T-cell differentiation. Eur J Immunol. 42(4):1044-50. Apr 2012 Chou FS, Griesinger A, Wunderlich M, Lin S, Link KA, Shrestha M, Goyama S, Mizukawa B, Shen S, Marcucci G, Mulloy JC.The THPO/MPL/Bcl-xL pathway is essential for survival and self-renewal in human pre-leukemia induced by AML1-ETO. Blood,(plenary paper) 120 (4): 2012. 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, 120 (4): 2012. Zhang Y, Yan X, Sashida G, Zhao X, Rao Y,Goyama S, Whitman SP, Zorko N, Bernot K, Conway RM, Witte D, Wang QF, Tenen DG, Xiao Z, Marcucci G, Mulloy JC, Grimes HL, Caligiuri MA, Huang G. Stress hematopoiesis reveals abnormal control of self-renewal, lineage bias, and myeloid differentiation in Mll partial tandem duplication (Mll-PTD) hematopoietic stem/progenitor cells. Blood. Aug 2 2012; 120(5):1118-29. Epub 2012 Jun 26.
Grants
Targeting Cdc42 in leukemia stem cells. Co-Principal Investigator. National Cancer Institute. Apr 2010 - Mar 2015. #1R01CA150547-01. Rac Signaling in MLL Leukemia. Principal Investigator. Leukemia and Lymphoma Society. Jul 2010 – Jun 2015. Cincinnati Center of Excellence in Molecular Hematology. Co-Director, Animal Core. National Institutes of Health. Sep 2010 – Jul 2015. # P30 DK090971. RUNX1 tumor suppressor as a therapeutic target in AML. Principal Investigator. Center for Clinical and Translational Science and Training, UC/CCHMC. Jul 2012 – Jun 2013. The role of bone marrow microenvironment in a humanized MDS mouse model. Co-Principal Investigator. Innovation Grant (Mulloy/Cancelas). CCHMC. 09/01/12 – 08/31/13. Genotype and phenotype of chemoresistant AML. Principal Investigator. NIH, NCI. 03/01/13 - 02/28/15. R21 CA168369. Hemostatic system components as novel therapeutic targets in childhood AML. Co-Principal Investigator. Center for Clinical and Translational Science and Training (Palumbo/Mulloy). 07/01/13 – 06/30/14. A Novel ROS-activated Therapeutic Modality for AML. Co-Principal Investigator. Center for Clinical and Translational Science and Training (Merino/Mulloy). 07/01/13 – 06/30/14. Validation and structural requirements of a novel anti-leukemia agent. Co-Principal Investigator. UC Technology Commercialization Accelerator (Merino/Mulloy). University of Cincinnati. 04/01/13 – 03/31/14 Efficacy and selectivity in combination of novel ROS activated anticancer agent. Co-Principal Investigator. University Research Council-UC (Merino/Mulloy). Interdisciplinary Faculty Research Support Grant. 04/01/13 – 03/31/14 Human IFN- Neutralization in Humanized NSGS Mice Developing Cytopenias. Principal Investigator. NovImmune (Mulloy/Jordan). 03/01/13 – 02/28/14. LSC mobilization and differentiation therapy. Co-Principal Investigator. Hyundai Hope On Wheels! (Mulloy/Mizukawa). 09/01/13 – 08/31/15.
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Nicolas Nassar, PhD
is a structural biologist interested in understanding the structure/function of signaling proteins, how they specifically bind and recognize regulators and targets, and in finding ways to inhibit their signaling in disease. His lab combines X-ray crystallography, site-directed mutagenesis, enzyme kinetics, and otherbiophysical techniques in its studies.
513-636-6597
nicolas.nassar@cchmc.org
Nicolas Nassar, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Biography
Nicolas Nassar, PhD is a structural biologist interested in the structure/function of signaling proteins and in finding ways to inhibit their signaling in disease. More specifically, we are interested in how a given protein specifically binds and recognizes its regulators and targets. We have over the years focused on Ras-like GTPases. Recently, however we have been interested in a new family of protein tyrosine phosphatases (PTPs). We combine X-ray crystallography, site-directed mutagenesis, enzyme kinetics, and other biophysical techniques in our studies.
Education and Training
PhD: University Joseph Fourier, Grenoble – France (1992).
Postdoc: Max Plank Institut, Dortmund – Germany (1996).
Research Associate: Cornell University, Ithaca – NY (2000).
Assistant Professor: Stony Brook University, NY (2006).
Research Assistant Professor: Stony Brook University (2010).
Publications
Jackoncic J, Sondgeroth B, Carpino N, Nassar N. The 1.35 Å structure of the Phosphatase domain of the Suppressor of T Cell Receptor Signaling Protein in complex with Sulfate. Acta Cryst section F66, 2010 643-647. Nassar N, Singh K, Garcia-Diaz M. Structure of the dominant negative S17N mutant of Ras. Biochemistry. 2010 49,1970-1974. Ford B, Boykevisch S, Zhao C, Kunzelmann S, Bar-Sagi D, Herrmann C, Nassar N. Characterization of a Ras mutant with identical GDP- and GTP-bound structures. Biochemistry. 2009 48,11449-11457. Carpino N, Chen Y, Nassar N, Hye-Won Oh. The Sts proteins target tyrosine phosphorylated, ubiquitinated proteins within TCR signaling pathways. in review. J. Immuno. 2009 46,3224-3231. Chen Y, Jakoncic J, Parker KA, Carpino N, Nassar N. Structures of the Phosphorylated and VO3-bound 2H-Phosphatase Domain of Sts-2. Biochemistry. 2009 48, 8129-8135. Chen Y, Jakoncic J, Carpino N, Nassar N. Structural and Functional Characterization of the 2H-phosphatase domain of Sts-2 reveals an Acid-Dependent Phosphatase Activity. Biochemistry. 2009 48,1681-1690. Chen Y, Jakoncic J, Keller J, Wang J, Zheng X, Carpino N, Nassar N. Structural and functional characterization of the C-terminal domain of the ecdysteroid phosphate phosphatase from Bombyx mori. Biochemistry. 2008 47,12135-12145. Mikhailik A, Ford B, Keller J, Chen Y, Nassar N, Carpino N. The C-terminal mutase-like domain of Sts-1 is important for its T-cell suppressor activity. Molecular Cell. 2007 27, 486-487.
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Dao Pan, PhD
has long term research interests in combining translational and basic research on virus-mediated gene transfer and disease treatment for Mucopolysaccharidoses disorders, which are often associated with systemic and central nerve system abnormalities, and early childhood death. Visit the Pan Lab.
513-636-6315
Dao.Pan@cchmc.org
Dao Pan, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Hematopoietic stem cells; Mesenchymal stem/progenitor cells; Gene therapy; Human genetics; Translational research; Lysosomal storage diseases Visit the Pan Lab.
Education and Training
PhD: University of Minnesota, Minneapolis, MN, 1997.
MS: Peking Normal University, Beijing, China, 1991.
BS: Peking Normal University, Beijing, China, 1988.
Publications
View PubMed Publications
Pan D*, Kalfa TA, Wang D, Risinger M, Crable S, Ottlinger A, Mount DB, Hubner CA, Franco RS, and Joiner CH*. KCl cotransporter gene expression during human and murine erythroid differentiation, J Biol Chem, 286(35): 30492-30503, 2011. co-correspondent authors. Pan D. Cell- and Gene-Based Therapeutic Approaches for Neurological Deficits in Mucopolysaccharidoses. Curr Pharm Biotechnol. 2011 Jan 11. 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. 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. Pan D. In situ (in vivo) gene transfer into murine bone marrow stem cells. Methods Mol Biol. 2009;506:159-69. Wang D, Worsham DN, Pan D. Co-expression of MGMT(P140K) and alpha-L-iduronidase in primary hepatocytes from mucopolysaccharidosis type I mice enables efficient selection with metabolic correction. J Gene Med. 2008 Mar;10(3):249-59. Pan D, Sciascia A 2nd, Vorhees CV, Williams MT. Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome. Brain Res. 2008 Jan 10;1188:241-53. Worsham DN, Schuesler T, von Kalle C, Pan D. In vivo gene transfer into adult stem cells in unconditioned mice by in situ delivery of a lentiviral vector. Mol Ther. 2006 Oct;14(4):514-24.
Grants
Comprehensive Sickle Cell Center. Co-investigator. National Heart, Lung, and Blood Institute. Apr 2008 - Mar 2013. #U54 HL070871. Genetic Therapy for CNS Manifestations in MPS I via BBB-Targeted Protein Delivery. Principal Investigator. National Institute of Neurological Disorders and Stroke. Sep 2008 - Aug 2013. #R01 NS064330.
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Qishen Pang, PhD
The Pang laboratory is focused on elucidating the mechanisms by which the Fanconi proteins regulate hematopoietic stem cells in the context of bone marrow failure and leukemia development. The goal of the research is to identify novel pharmaceutical targets for the treatment of patients with Fanconi anemia and other bone marrow failure syndromes. Several current projects will utilize cellular, genetic, and molecular techniques to identify and characterize critical pathways that regulate hematopoietic stem cells function, using knockout mice and xenotransplant models. Visit the Pang Lab
513-636-1152
qishen.pang@cchmc.org
Qishen Pang, PhD
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Education and Training
PhD: Oregon State University, Corvallis, Oregon, 1993.
Postdoctoral Fellow: Oregon Health Sciences University, Portland, OR, 2000.
Publications
View PubMed Publications
Du W, Li XE, Sipple J, Pang Q. Overexpression of IL-3R{alpha} on CD34+CD38- stem cells defines leukemia-initiating cells in Fanconi anemia AML. Blood. 2011 Apr 21;117(16):4243-52.
Du W, Li J, Sipple J, Chen J, Pang Q. Cytoplasmic FANCA-FANCC complex interacts and stabilizes the cytoplasm-dislocalized leukemic nucleophosmin protein (NPMc). J Biol Chem. 2010 Nov 26;285(48):37436-44.
Li J, Du W, Maynard S, Andreassen PR, Pang Q. Oxidative stress-specific interaction between FANCD2 and FOXO3a. Blood. 2010 Feb 25;115(8):1545-8. Du W, Zhou Y, Pike S, Pang Q. NPM phosphorylation stimulates Cdk1, overrides G2/M checkpoint and increases leukemic blasts in mice. Carcinogenesis. 2010 Feb;31(2):302-10. Pang Q, Andreassen PR. Fanconi anemia proteins and endogenous stresses. Mutat Res. 2009 Jul 31;668(1-2):42-53.
Rani R, Li J, Pang Q. Differential p53 engagement in response to oxidative and oncogenic stresses in Fanconi anemia mice. Cancer Res. 2008 Dec 1;68(23):9693-702. Zhou Y, Du W, Koretsky T, Bagby GC, Pang Q. TAT-mediated intracellular delivery of NPM-derived peptide induces apoptosis in leukemic cells and suppresses leukemogenesis in mice. Blood. 2008 Sep 15;112(6):2474-83.
Zhang X, Shang X, Guo F, Murphy K, Kirby M, Kelly P, Reeves L, Smith FO, Williams DA, Zheng Y, Pang Q. Defective homing is associated with altered Cdc42 activity in cells from patients with Fanconi anemia group A. Blood. 2008 Sep 1;112(5):1683-6. Li J, Sejas DP, Zhang X, Qiu Y, Nattamai KJ, Rani R, Rathbun KR, Geiger H, Williams DA, Bagby GC, Pang Q. TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells. J Clin Invest. 2007 Nov;117(11):3283-95.
Zhang X, Sejas DP, Qiu Y, Williams DA, Pang Q. Inflammatory ROS promote and cooperate with the Fanconi anemia mutation for hematopoietic senescence. J Cell Sci. 2007 May 1;120(Pt 9):1572-83.
Grants
Role of tumor necrosis factor in leukemogenesis. Leukemia and Lymphoma Society. July 2008 - Jun 2013. Role of FA proteins in hematopoiesis. National Institutes of Health. May 2005 - Apr 2015. Targeted improvement in stem cell therapy for leukemia and bone marrow failure syndromes. National Institutes of Health. Feb 2011 - Jan 2016.
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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
Nancy Ratner, PhD
Beatrice C. Lampkin Chair, Cancer Biology
Academic Information
Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsDevelopment of the nervous system; peripheral nerve tumor formation Research InterestsGenetic mutations in tumor suppressor genes Visit the Ratner Lab.
Biography
Dr. 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 as a potential therapeutic target 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 - 2004. Dr. Ratner is currently a professor in the Department of Pediatrics, Cincinnati Children’s Hospital, University of Cincinnati, and the program leader for Cancer Biology and Neural Tumors Program in the Cancer and Blood Disorders 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 – 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.
Education and Training
PhD: Indiana University, 1982. BA: Brown University, 1975. Fellowship: Washington University St. Louis, 1982-1987.
Publications
View PubMed Publications
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. Shang X, Cancelas JA, Li L, Guo F, Liu W, Johnson JF, Ficker A, Daria D, Geiger H, Ratner N, Zheng YR-Ras and Rac1 GTPase Crosstalk Regulates Hematopoietic Progenitor Cell Migration, Homing and Mobilization. Biol Chem. 2011 May 13. Wu., J., Dombi, E.,Jousma, E., Dunn, S.R., Lindquist, D., Kim, M., Kim, A., Cripe, T.P., and Ratner, N. Magnetic resonance imaging to monitor effects of Sorafenib and RAD001 in the DhhCre;Nf1fl/fl mouse model of plexiform neurofibroma. Ped. Blood & Cancer. 2011. Hummel, T.R., Jessen, W.J., Miller, S.C., Kluwe, L, Mautner, V.F., Wallace, M.R., Lázaro, C. Page, G., Worley, P., Aronow, B.J., Schorry, E., and Ratner, N. Gene expression analysis identifies potential biomarkers of neurofibromatosis type 1 including adrenomedullin. Clin Cancer Res. 2010;16 5048-5057. Ryan, M.A., Nattamai, K.J., Xing, E., Schleimer, D., Daria, D., Sengupta, A., Köhler, A., Liu, W., Gunzer, M., Jansen, M., Ratner, N., Le Cras, T.D., Waterstrat, A., Van Zant,G., Cancelas, J.A., Zheng, Y., and Geiger, H. Pharmacological inhibition of EGFR signaling enhances G-CSF induced hematopoietic stem cell mobilization. Nature Med., 2010 16(10):1141-6. 2010. Miller, S.J., Lan, Z., Hardiman, A., Wu, J., Kordich, J.J., Patmore, D., Hegde, R., Cripe, T.P., Cancelas, J., Collins M. and Ratner, N. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 29(3):368-79. 2009. Miller, S.J., Jessen, W.J., Mehta, T., Hardiman, A., Sites, E., Kaiser, S., Jegga, A., Li, H., Upadhyaya, M.., Giovannini, M., Muir, D., Wallace, M.R., Lopez, E., Serra, E., Lazaro, C., Stemmer-Rachamimov, A., Page, G., Aronow, B.J. and Ratner, N. Integrative genomic analyses of neurofibromatosis tumors identify SOX9 as biomarker and survival gene. EMBO Mol. Medicine. 1(4): 236-248. 2009. Mahller, Y., Williams, J., Baird, W., Mitton, B., Grossheim, J., Saeki, Y., Cancelas, J., Ratner, N., and Cripe, T. Neuroblastoma cell lines contain pluripotent tumor initiating cells that are susceptible to a targeted oncolytic virus. PLoS ONE. 4(1):e4235, 1 – 10. 2009. Williams, J.P., Wu, J., Johansson, G., Rizvi, T., Miller, S.C., Geiger, H., Malik, P., Li, W., Mukouyama, Y., Cancelas, J.A. and Ratner, N. Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor population that confers neurofibroma tumorigenic potential. Cell Stem Cell. 3(6):658-69. 2008. Williams, J.P., Wu, J., Johansson, G., Rizvi, T., Miller, S.C., Geiger, H., Malik, P., Li, W., Mukouyama, Y., Cancelas, J.A. and Ratner, N. Nf1 mutation expands an EGFR-dependent peripheral nerve progenitor population that confers neurofibroma tumorigenic potential. Cell Stem Cell. 3(6):658-69. 2008. Johansson, G., Mahller, Y., Collins, M.H., Kim, M-O., Nobukuni, T., Perentesis, J.P., Cripe, T.P., Lane, H.A., Kozma, S., Thomas, G., Ratner, N. Effective In Vivo Targeting of the mTOR Pathway in Malignant Peripheral Nerve Sheath Tumor. Mol. Cancer Therapeutics. 7(5):1237-45. 2008.
Grants
NIH-R01 NS 28840-20, "Mitogenic Activities in Neurofibromatosis", 9/2011 - 9/2016 (Ratner, PI) NIH-R01 CA118032-04, "Schwann cells in Neurofibromatosis type 2", 7/2007 - 6/2012 (Ratner, PI) NIH-P50-NS057531-03, "Cincinnati Center for Neurofibromatosis Research", 7/2008 - 6/2013 (Ratner, PI) Children's Tumor Foundation, "Preclinical Testing of Neurofibroma and MPNST", 7/2009 - 6/2011 (Cripe, PI, Ratner, Co-PI) U.S. Army NF Program, NF080052, "Therapeutic Targets for Peripheral Nerve Tumors: NF1, NF2, and Schwannomatosis", 3/2009 - 9/2011 (Ratner, PI) U.S. Army NF Program, DOD W81XWH-10-1-0116, "Modeling the Brain in NF1", 4/2010 - 3/2013 (Ratner, PI)
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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
Daniel T. Starczynowski, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
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.
Education and Training
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.
Publications
View PubMed Publications
Starczynowski DT, Vercauteren S, Sung S, Brooks-Wilson A, Lam WL, Karsan A. Copy number alterations at polymorphic loci may be acquired somatically in patients with myelodysplastic syndromes. Leuk Res. 2011 Apr;35(4):444-7. Starczynowski DT, Kuchenbauer F, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK, Karsan A. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 2011 Feb;39(2):167-178.e4. 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, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK, Karsan A. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 2011 Feb;39(2):167-178. Vercauteren SM, Sung S, Starczynowski DT, Lam WL, Bruyere H, Horsman DE, Tsang P, Leitch H, Karsan A. Array comparative genomic hybridization of peripheral blood granulocytes of patients with myelodysplastic syndrome detects karyotypic abnormalities. Am J Clin Pathol. 2010 Jul;134(1):119-26.
Starczynowski DT and A Karsan. Innate immune signaling in Myelodysplastic Syndromes. Hematology/Oncology Clinics of North America. 2010 Apr;24(2):343-359.
Starczynowski DT and A Karsan. Deregulation of innate immune signaling in myelodysplastic syndromes is associated with deletion of chromosome arm 5q. Cell Cycle. 2010 Mar;9(5):855-6.
Starczynowski DT, F Kuchenbauer, B Argiropoulos, S Sung, R Morin, A Muranyi, D Hogue, R Wells, M Marra, WL Lam, K Humphries, and A Karsan. Identification of miR-145 and miR-146a as microRNAs involved in the pathogenesis of 5q- syndrome. Nature Medicine. 2010Jan;16(1):49-58.
Starczynowski DT, S Vercauteren, S Sung, A Brooks-Wilson, J Spinelli, C Eaves, A Eaves, D Horsman, W Lam, A Karsan. 2008. High-resolution array comparative genomic hybridization of CD34+ cells from patients with low-risk myelodysplastic syndromes predicts overall and leukemia-free survival. Blood. 2010 Oct;112(8): 3412-3424.
Starczynowski DT, Trautmann H, Pott C, Harder L, Arnold N, Africa JA, Leeman JR, Siebert R, Gilmore TD. Mutation of an IKK phosphorylation site within the transactivation domain of REL in two patients with B-cell lymphoma enhances REL's in vitro transforming activity. Oncogene. 2007 Apr 26;26(19):2685-94. Starczynowski DT, Reynolds JG, Gilmore TD. Mutations of tumor necrosis factor alpha-responsive serine residues within the C-terminal transactivation domain of human transcription factor REL enhance its in vitro transforming ability. Oncogene. 2005 Nov 10;24(49):7355-68.
Grants
Regulation and Function of TIFAB in Myelodysplastic Syndrome. Department of Defense. Jun 2011 - May 2014. #W81XWH1110468.
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Johannes van der Loo, PhD
Director, Aseptic Processing Laboratories
is director of the Aseptic Processing Laboratories, director of the Viral Vector Core and chair of the Institutional Biosafety Committee. His team continues to provide both GMP and Research-grade viral vector products to investigators locally, nationally and internationally using a fee-for-service model.
513-803-1066
Han.vanderloo@cchmc.org
Johannes van der Loo, PhD
Director, Aseptic Processing Laboratories
Director, Vector Production Facility
Director, Research Viral Vector Core
Academic Information
UC Department of Pediatrics
Field Service Associate Professor
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Specialties
Development, scale-up and clinical production of viral vectors and cellular products
Biography
Dr. van der Loo has been employed by Cincinnati Children's since 2002 where he is the Director of the Aseptic Processing Laboratories, an ISO Class 7 and 8 cleanroom facility for the manufacture of GMP-grade viral vectors and manipulation of GMP/GTP-grade cellular products for phase I/II Clinical Trials in compliance US federal and European guidelines. In addition, he is the Director of the Vector Production Facility, the Director of the Research Viral Vector Core and the Chair of the CCHMC Institutional Biosafety Committee (IBC). His previous appointment as Assistant Professor (1998-2002) was with the Department of Hematology/Oncology and Transplantation, at the University of Minnesota School of Medicine, in Minneapolis, MN. Dr. van der Loo is the Director of the Cincinnati Children's Hospital Medical Center's Aseptic Processing Laboratories, Vector Production Facility and Research Viral Vector Core.
Education and Training
BS: Biology, State University of Utrecht, the Netherlands, 1983. MS: Medical Biology, State University of Utrecht, the Netherlands, 1987. Teaching degree: Biology, State University of Utrecht, Netherlands, 1989. PhD: Hematology, Erasmus University Rotterdam, the Netherlands, 1995. Postdoctoral Fellowship: Hematology, Howard Hughes Medical Institute, Indiana University, Indianapolis, IN, 1994-1998.
Publications
View PubMed Publications
van der Loo JC, Swaney WP, Grassman E, Terwilliger A, Higashimoto T, Schambach A, Baum C, Thrasher AJ, Williams DA et al. Scale-up and manufacturing of clinical-grade self-inactivating gamma-retroviral vectors by transient transfection. Gene Ther. 2012;19(3):246-254. van der Loo JC, Swaney WP, Grassman E, Terwilliger A, Higashimoto T, Schambach A, Baum C, Thrasher AJ, Cavazzana-Calvo M, Hacein-Bey-Abina S, Williams DA, Nordling DL, Reeves L, Malik P. Critical variables affecting clinical-grade production of the self-inactivating gamma-retroviral vector for the treatment of X-linked severe combined immunodeficiency. Gene Ther. 2012;19(8):872-876. Schambach A, Swaney WP, van der Loo JC. Design and production of retro- and lentiviral vectors for gene expression in hematopoietic cells. Methods Mol Biol. 2009;506:191-205.
Suzuki T, Sakagami T, Rubin BK, Nogee LM, Wood RE, Zimmerman SL, Smolarek T, Dishop MK, Wert SE, Whitsett JA, Grabowski G, Carey BC, Stevens C, van der Loo JC, Trapnell BC. Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA. J Exp Med. 2008 Nov 24;205(12):2703-10.
Carey B, Staudt MK, Bonaminio D, van der Loo JC, Trapnell BC. PU.1 redirects adenovirus to lysosomes in alveolar macrophages, uncoupling internalization from infection. J Immunol. 2007 Feb 15;178(4):2440-7.
Grants
Novel Scalable Vector Production Systems Development Core. Principle Investigator. CCTST PCS T1 Pilot Collaborative Studies Grant funded by Institutional Clinical and Translational Science Award, NIH/NCRR. Jul 2013 - Jun 2015. 8UL1TR000077-04.
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Ronald R. Waclaw, MS, PhD
is a developmental neurobiologist who has a research program in forebrain development and function. His lab studies the molecular genetic mechanisms in forebrain progenitor cell differentiation. One focus of his lab is to determine the effect of known “RASopathy” genes, which result in abnormalities in RAS/MAPK signaling, on brain development and brain tumor formation.
513-803-3336
ronald.waclaw@cchmc.org
Ronald R. Waclaw, MS, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Forebrain progenitor cell differentiation; “RASopathy” genes
Education and Training
BA: Biology, North Central College, Naperville, IL 1997.
MS: Department of Biology, Ball State University, Muncie, IN, 1997-1999.
PhD:Molecular and Developmental Biology, University of Cincinnati, Cincinnati, OH, 1999-2005.
Fellowship: Division of Developmental Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 2005-2010.
Publications
View PubMed Publications
Jeong Y, Dolson DK, Waclaw RR, Matise MP, Sussel L, Campbell K, Kaestner KH, and Epstein DJ. Spatial and temporal requirements for sonic hedgehog in the regulation of thalamic interneuron identity. Development. 2011;138:531-541
Waclaw RR, Ehrman LA, Pierani A, Campbell K. Developmental origin of the neuronal subtypes that comprise the amygdalar fear circuit in the mouse. J Neurosci. 2010 May 19;30(20):6944-53.
Xu Q, Guo L, Moore H, Waclaw RR, Campbell K, Anderson SA. Sonic Hedgehog confers ventral telencephalic progenitors with distinct cortical interneuron fates. Neuron. 2010 Feb;65(3):328-340.
Waclaw RR, Campbell K. Regional control of cortical lamination. Nat Neurosci. 2009 Oct;12(10):1211-2.
Waclaw RR, Wang B, Pei Z, Ehrman LA, Campbell K. Distinct temporal requirements for the homeobox gene Gsx2 in specifying striatal and olfactory bulb neuronal fates. Neuron. 2009 Aug 27;63(4):451-65.
Wang B, Waclaw RR, Allen ZJ 2nd, Guillemot F, Campbell K. Ascl1 is a required downstream effector of Gsx gene function in the embryonic mouse telencephalon. Neural Dev. 2009 Feb 10;4:5.
Allen ZJ 2nd, Waclaw RR, Colbert MC, Campbell K. Molecular identity of olfactory bulb interneurons: transcriptional codes of periglomerular neuron subtypes. J Mol Histol. 2007 Dec;38(6):517-25.
Chen L, Liao G, Waclaw RR, Burns KA, Linquist D, Campbell K, Zheng Y, Kuan CY. Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons. J Neurosci. 2007 Apr 4;27(14):3884-93.
Waclaw RR, Allen ZJ 2nd, Bell SM, Erdélyi F, Szabó G, Potter SS, Campbell K. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Neuron. 2006 Feb 16;49(4):503-16.
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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
Susanne Wells, PhD
Director, Epithelial Carcinogenesis and Stem Cell Program
Director, Postdoctoral Office
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
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.
Education and Training
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.
Publications
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Privette Vinnedge, L. M., Kappes, F., Nassar, N. and Wells, S. I. 2012. Stacking the DEK: from chromatin topology to cancer stem cells. Cell Cycle. In process. Romick-Rosendale, L. E., Lui, V. W., Grandis, J. R., and Wells, S. I. 2012. The Fanconi anemia pathway: repairing the link between DNA damage and squamous cell carcinoma. Mutation Research. In press. Privette Vinnedge, L. M., Ho, S.-M., Wikenheiser-Brokamp, K. A., Wells, S. I. 2012. The DEK oncogene is a target of steroid hormone receptor signaling in breast cancer. PLOS ONE, In process. Yablonska, S., Hoskins, E. E., Wells, S. I., Khan, S. A. 2012. Identification of miRNAs dysregulated in human foreskin keratinocytes (HFKS) expressing the human papillomavirus (HPV) Type 16 E6 and E7 oncoproteins. Epub ahead of print. Hoskins, E. E., Morreale, R. J., Werner, S. P., Higginbotham, J. M., Laimins, L. A., Lambert, P. F., Brown, D. R., Gillison, M. L., Nuovo, G. J., Witte, D. P., Kim, M.-O, Davies, S. M., Mehta, P. A., Butsch Kovacic, M., Wikenheiser-Brokamp, K. A., Wells, S. I. 2012. The Fanconi anemia pathway limits human papillomavirus replication. Journal of Virology. 86; 8131-8138 Wise-Draper, T. M., Draper, D. J., Gutkind, J. S., Molinolo, A. A., Wikenheiser-Brokamp, K. A., and Wells, S. I., 2012. Future directions and treatment strategies for head and neck squamous cell carcinomas. Transl. Res. 160; 167-177. Morrison, M. A., Morreale, R. J., Akunuru, S., Kofron, M., Zheng, Y., Wells, S. I. 2011. Targeting the human papillomavirus E6 and E7 oncogenes through expression of the BPV1 E2 protein stimulates cellular motility. Journal of Virology. 85: 10487-10498. Kavanaugh, G. M., Wise-Draper, T. M., Morreale, R. J., Morrison, M. A., Gole, B., Schwemberger, S., Tichy, E. D., Lu, L., Babcock, G. F., Wells, J. M., Drissi, R., Bissler, J. J., Stambrook, P. J., Andreassen, P. R., Wiesmüller, L., Wells, S. I. 2011. The human DEK oncogene regulates DNA damage response signaling and repair. Nucl. Acids Res. 39: 7465-7476. Privette Vinnedge, L. M., McClaine, R., Wagh, P. K., Wikenheiser-Brokamp, K. A., Waltz, S. E., Wells, S. I. 2011. The human DEK oncogene stimulates b-catenin signaling, invasion and mammosphere formation in breast cancer. Oncogene. 30: 2741-2752. Spence, J. R., Mayhew, C. N., Rankin, S. A., Kuhar, M. F., Vallance, J. E., Tolle, K., Hoskins, E. E., Kalinichenko, V. V., Wells, S. I., Zorn, A. M., Shroyer, N. F., and Wells, J. M. 2011. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature. 470: 105-109.
Grants
Role and regulation of the human DEK proto-oncogene. Principle Investigator. National Institutes of Health. 2006 - 2011. Fanconi Anemia and HPV transformation. Principle Investigator. National Institutes of Health. 2010 - 2015. #2RO1 CA102357. Fanconi Anemia as a Model for Susceptibility to Human Papillomavirus Infection. Principle Investigator. National Institutes of Health. 2011 - 2016. #1RO1 HL108102-01.
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Jianqiang Wu, MD, MS
Academic Information
Instructor, UC Department of Pediatrics
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Specialties
Preclinical therapeutic trial on neurofibroma; cancer stem cell(s) in neurofibroma
Education and Training
MD: Soochow University College of Medicine, SooChow, P.R. China, 1991.
MS: Soochow University College of Medicine, SooChow, P.R. China, 1996.
Publications
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Miller SJ, Lan ZD, Hardiman A, Wu J, Kordich JJ, Patmore DM, Hegde RS, Cripe TP, Cancelas JA, Collins MH, Ratner N. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene. 2010 Jan 21;29(3):368-79.
Ren XP, Wu J, Wang X, Sartor MA, Qian J, Jones K, Nicolaou P, Pritchard TJ, Fan GC. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation. 2009 May 5;119(17):2357-66. Kurth CD, McCann JC, Wu J, Miles L, Loepke AW. Cerebral oxygen saturation-time threshold for hypoxic-ischemic injury in piglets. Anesth Analg. 2009 Apr;108(4):1268-77.
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. Wu J, Williams JP, Rizvi TA, Kordich JJ, Witte D, Meijer D, Stemmer-Rachamimov AO, Cancelas JA, Ratner N. Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells. Cancer Cell. 2008 Feb;13(2):105-16. Wu J, Bohanan CS, Neumann JC, Lingrel JB. KLF2 transcription factor modulates blood vessel maturation through smooth muscle cell migration. J Biol Chem. 2008 Feb 15;283(7):3942-50.
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.
Wu J. Deep sedation with intravenous infusion of combined propofol and ketamine during dressing changes and whirlpool bath in patients with severe epidermolysis bullosa. Paediatr Anaesth. 2007 Jun;17(6):592-6.
Nelson LA, McCann JC, Loepke AW, Wu J, Ben Dor B, Kurth CD. Development and validation of a multiwavelength spatial domain near-infrared oximeter to detect cerebral hypoxia-ischemia. J Biomed Opt. 2006 Nov-Dec;11(6):064022.
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