University of Cincinnati Department of Pediatrics

David A. Hildeman, PhD

Appointment

Assistant Professor, University of Cincinnati College of Medicine

Email

david.hildeman@cchmc.org

Phone

513-636-3923

Fax

513-636-5355

Credentials

BS Biology, University of Wisconsin-Stevens Point, Stevens Point, Wis., 1991.

PhD Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, Wis., 1997

Position History

2008-Present: Associate Professor. Division of Immunobiology, Department of Pediatrics. University of Cincinnati College of Medicine and Cincinnati Children's Hospital Research Foundation. Cincinnati, OH.

2002-2008: Assistant Professor. Division of Immunobiology, Department of Pediatrics, University of Cincinnati College of Medicine and Children's Hospital Medical Center, Cincinnati, OH 45229.

1997-2002: Postdoctoral Fellow. Howard Hughes Medical Institute. Laboratory of Philippa Marrack, Ph.D. and John Kappler, Ph.D., Denver, CO.

Research

Our lab is primarily interested in molecular factors that control the decision between tolerance and immunity within T lymphocytes. We use staphylococcal enterotoxins, recombinant vaccinia viruses, lymphocytic choriomeningitis virus and MHC tetrameric reagents as tools to study antigen -specific T cell responses. Our interest in tolerance centers on regulation of mechanisms that control the survival and death of activated T cells in vivo, namely Bcl-2 and its antagonist Bim. We are also interested in the manipulation and regulation of antigen-specific T cell responses via novel vaccine strategies to either induce tolerance or enhance immunity. Finally, we are interested in mechanisms underlying sex-based differences in T cell responses and how these differences relate to autoimmune disease.

Research Grants and Contracts

RO1 AI056927 - CD40 Ligand Dysregulation and HIV Pathogenesis. January 1, 2005 – December 31, 2009. NIH/NIAID. PI: Claire Chougnet.

R01 AI057753 - Regulation of Apoptosis in Activated Primary T Cells. Dec. 1st, 2008 – Nov 30th, 2013. NIH/NIAID. PI: David Hildeman.

RO1 AI067903 - TGF- in T cell homeostasis and tolerance. February 1, 2006 – November 30, 2010. NIH/NIAID. PI: Thomas Doetschman.

RO1 CA114004 - Oncolytic viral therapy for rhabdomyosarcoma. June 1, 2006-May 30, 2010. NIH/NCI. PI: Timothy Cripe.

Midwest Microbial Pathogenesis Center Grant - Mechanisms underlying IL-7-driven protection during polymicrobial sepsis. Sept. 15th, 2009 - Sept 14th, 2010.
PI: David Hildeman.

RO1 AG3054748 - Homeostasis and function of regulatory T cells in aging. Sept 15, 2009 - Aug. 31st, 2011. NIH/NIA. Co-PIs: Claire Chougnet, David Hildeman.

Publications, Most Recent

Find a full listing of publications by Dr. Hildeman on PubMed

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

Lin, A., P.K. Tripathi, A. Sholl, M. Jordan, and D. Hildeman. IFN signaling in macrophage-lineage cells regulates CNS inflammation and chemokine production. J. Virol. 83(17):8604-15. 2009.

Morris, S.C., S.M. Heidorn, D. R. Herbert, C. Perkins, D. A. Hildeman, M. V. Khodoun, and F. Finkelman. Endogenously produced IL-4 nonredundantly stimulates CD8+ T cell proliferation. J. Immunol. 182(3):1429-382. 2009.

Hildeman, D. and E. Janssen. Interferon and self adsorbed CD4+ T cells: a regulatory double negative. Nature Immunol. 9(11):1210-1212. 2008.

Guo, F. J.A. Cancelas, D. Hildeman, D.A. Williams, and Y. Zheng. Rac GTPase isoforms, Rac1 and Rac2, play a redundant and crucial role in T-cell development. Blood. 112(5):1767-75. 2008.

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

Machado, F.S, L. Esper, A. Dias, R. Madan, D. Hildeman, C.N. Serhan, C. Karp, and J. Aliberti. Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6. J. Exp Med. 205(5):1077-1086 2008.

Zarebski, A., C.S. Velu, A. M. Baktula, T. Bourdeau, S.R. Horman, S. Basu, M.S. Horwitz, D. Hildeman, J. Trent, and H. L. Grimes. The human severe congential neutropenia-associated Gfi1N382S mutant blocks murine granulopoiesis through CSF1. Immunity 29(3):370-380. 2008.

Reckling, S., S. Divanovic, S. Wojciechowski, C. L. Karp, Y. Belkaid, and D. Hildeman. Pro-apoptotic Bcl-2 family member Bim promotes persistent infection and limits protective immunity. Inf. Immun. 76(3):1179-85. 2008.

Wojciechowski, S., P. Tripathi, T. Bourdeau, L. Acero, H. L. Grimes, J. Katz, F. D. Finkelman, and D. Hildeman. Bim/Bcl-2 balance is critical to maintain naïve and memory T cell homeostasis. J. Exp. Med. 204(7):1665-1675. 2007.

Hildeman, D., T. Jorgensen, J. Kappler, and P. Marrack. Apoptosis and the homeostatic control of immune responses. Curr Op. Immunol. 19(5):516-521. 2007.

DeKoter, R.P., B. L. Schweitzer, M.B. Kamath, D.A. Jones, H. Tagoh, C. Bonifer, D.A. Hildeman and K.J. Huang. Regulation of the IL-7 receptor alpha promoter by the Ets transcription factors PU.1 and GA binding protein in developing B cells. J. Biol. Chem. 282(19):14194-204. 2007.

Chougnet, CA and D. Hildeman. “It’s hard to get downstream without a raft: A commentary on “Reactive oxygen species promote raft formation in T lymphocytes”. Free Radic. Biol. Med. 42(7):933-935. 2007.

Hildeman. Contraction of CD4+ T cell responses is not controlled by limiting amounts of IL-7. J. Immunol. 178:4027-4031. 2007.

Grayson JM, Weant AE, Holbrook BC, Hildeman D. Role of Bim in regulating CD8+ T-cell responses during chronic viral infection.J Virol 80:8627-38. 2006.

Gu Y, Chae HD, Siefring JE, Jasti AC, Hildeman DA, Williams DA. RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development.Nat Immunol 7:1182-1190. 2006.

Zhu Y, Liu X, Hildeman D, Peyerl FW, White J, Kushnir E, Kappler J, Marrack P. Bax does not have to adopt its final form to drive T cell death.J Exp Med 203:1147-52. 2006.

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

Tripathi P, Madan R, Chougnet C, Divanovic S, Ma X, Wahl LM, Gajewski T, Karp CL, Hildeman DA. An adenoviral vector for probing promoter activity in primary immune cells.J Immunol Methods 311:19-30. 2006.

Presentations, Most Recent

Roles of Bim and Bcl-2 in control of T cell homeostasis. Duke University School of Medicine. Department of Immunology Seminar Series. Durham, NC. 2008.

Apoptotic control of T cell homeostasis. Indiana University School of Medicine. Department of Microbiology and Immunology Seminar Series. Indianapolis, IN. 2008.

Regulation of T cell homeostasis by Bim and Bcl-2. Keystone Meeting: Cell Death in the Immune System. Breckenridge, CO. 2008.

Control of T cell apoptosis – integrated roles of Bim, Bcl-2 and reactive oxygen species. Department of Toxicology Seminar Series. Wright State University, Dayton, OH. 2007.

Contraction of CD4+ T cell responses is not controlled by limiting amounts of IL-7. Keystone Meeting: Immunological Memory. Sante Fe, NM. 2007.

Apoptotic control of T cell homeostasis. 13th International Congress of Immunology. Rio de Janiero, Brazil. 2007.

Bcl-2 family members and control of T cell homeostasis. Washington University School of Medicine. Department of Anesthesiology Seminar Series. St. Louis, MO. 2007.

Apoptotic control of T cell homeostasis. St. Louis University School of Medicine. Department of Microbiology and Immunology Seminar Series. St. Louis, MO. 2007.

Molecular control of T cell homeostasis in vivo. University of Alabama at Birmingham, Department of Microbiology Visiting Professor Seminar Series. Birmingham, AL. 2006.

Professional Organization Memberships

American Association of Immunologists

The International Cell Death Society

Federation of American Societies for Experimental Biology

Special Interests

T cells, autoimmunity, sex differences in immune responses, apoptosisEditorial Positions

Ad hoc reviewer for Blood
Ad hoc reviewer for American Journal of Respiratory Cell and Molecular Biology
Ad hoc reviewer for Proceedings of the National Academy of Sciences (USA)
Ad hoc reviewer for Trends in Immunology
Ad hoc reviewer for Frontiers in Bioscience
Ad hoc reviewer for International Imunology
Ad hoc reviewer for Biochimica et Biophysica Acta - Molecular Cell Research
Ad hoc reviewer for Molecular Therapy
Ad hoc reviewer for Journal of Leukocyte Biology
Ad hoc reviewer for International Journal of Cancer
Ad hoc reviewer for Free Radical Biology and Medicine