University of Cincinnati Department of Pediatrics

David A. Hildeman, PhD

Appointment

Assistant Professor

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

1993-1997: Research Assistant. University of Wisconsin-Madison. Department of Medical Microbiology and Immunology. Laboratory of Daniel Muller, MD, PhD.1997-2002: Postdoctoral Fellow. Howard Hughes Medical Institute. Laboratory of Philippa Marrack, PhD and John Kappler, PhD.

2002-Present: Assistant Professor. Division of Immunobiology. Children's Hospital Medical Center, Cincinnati, OH 45229.

Awards and Honors

1997-2002 Howard Hughes Postdoctoral Fellowship

2000-01 Janet S. Lewald Fellowship in Basic Immunology

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

Co-Investigator: "Protective Antigens from Histoplasma capsulatum." (NIH/NIAID RO1 AI 034361)
7/01/03-12/31/07Our role in this grant is to identify epitopes from Histoplasma capsulatum that bind to I-Ab, to create MHC-tetrameric staining reagents to identify H. capsulatum-specific T cells, and to determine their functional roles during immune responses in vivo.
Principal Investigator: George Deepe

Principal Investigator: "Pilot and Feasibility Core. Tracking Autoreactive T cells in Collagen Induced Arthritis." (NIH/NIDDK P30 AR47363.)
3/15/04-3/15/06The goal of this grant is to determine the mechanism by which soluble peptide//MHC/IgG3 fusion proteins block autoimmune disease in a mouse model of rheumatoid arthritis. We will create MHC-tetrameric reagents and track the fate of autoreactive T cells with and without treatment with soluble MHC molecules.
Principal Investigator: Susan Thompson

Consultant: "Prophylactic and therapeutic applications of MnTBAP in HIV infection." (Translational Research Initiative Grant/Cincinnati Children's Research Foundation.)
7/01/04-5/31/05The goal of this grant is to determine the mechanism(s) by which the antioxidant, MnTBAP, provides protection of human CD4+ T cells against HIV infection.
Principal Investigator: Claire Chougnet

Co-Investigator: "CD40 Ligand Dysregulation and HIV Pathogenesis." (NIH/NIAID RO1 AI056927)
1/01/05-12/31/09The goal of this grant is to determine the molecular mechanisms by which HIV gp120 - T cell CD4 interactions ablate induction of CD40L. We will create retroviruses expressing dominant negative and constitutively active signaling molecules to manipulate T cell signaling pathways to overcome the effects of HIV gp120 on CD40L induction.
Principal Investigator: Claire Chougnet

Publications, Most Recent

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

Grayson JM, Weant AE, Holbrook BC, Hildeman D. (2006) Role of Bim in regulating CD8+ T-cell responses during chronic viral infection.J Virol 80:8627-38.
Gu Y, Chae HD, Siefring JE, Jasti AC, Hildeman DA, Williams DA. (2006) RhoH GTPase recruits and activates Zap70 required for T cell receptor signaling and thymocyte development.Nat Immunol 7:1182-1190.
Zhu Y, Liu X, Hildeman D, Peyerl FW, White J, Kushnir E, Kappler J, Marrack P. (2006) Bax does not have to adopt its final form to drive T cell death.J Exp Med 203:1147-52.
Wojciechowski S, Jordan MB, Zhu Y, White J, Zajac AJ, Hildeman DA. (2006) Bim mediates apoptosis of CD127(lo) effector T cells and limits T cell memory.Eur J Immunol 36:1694-706.
Tripathi P, Madan R, Chougnet C, Divanovic S, Ma X, Wahl LM, Gajewski T, Karp CL, Hildeman DA. (2006) An adenoviral vector for probing promoter activity in primary immune cells.J Immunol Methods 311:19-30.
Fuller MJ, Hildeman DA, Sabbaj S, Gaddis DE, Tebo AE, Shang L, Goepfert PA, Zajac AJ. (2005) Cutting edge: emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell help.J Immunol 174:5926-30.
Hawlisch H, Belkaid Y, Baelder R, Hildeman D, Gerard C, Kohl J. (2005) C5a negatively regulates toll-like receptor 4-induced immune responses.Immunity 22:415-26.
Tripathi P, Hildeman D. (2004) Sensitization of T cells to apoptosis--a role for ROS?Apoptosis 9:515-23.
Zhu Y, Swanson BJ, Wang M, Hildeman DA, Schaefer BC, Liu X, Suzuki H, Mihara K, Kappler J, Marrack P. (2004) Constitutive association of the proapoptotic protein Bim with Bcl-2-related proteins on mitochondria in T cells.Proc Natl Acad Sci U S A 101:7681-6.
Gardai SJ, Hildeman DA, Frankel SK, Whitlock BB, Frasch SC, Borregaard N, Marrack P, Bratton DL, Henson PM. (2004) Phosphorylation of Bax Ser184 by Akt regulates its activity and apoptosis in neutrophils.J Biol Chem 279:21085-95.
Hildeman DA. (2004) Regulation of T-cell apoptosis by reactive oxygen species.Free Radic Biol Med 36:1496-504.
Zhang R, Fichtenbaum CJ, Hildeman DA, Lifson JD, Chougnet C. (2004) CD40 ligand dysregulation in HIV infection: HIV glycoprotein 120 inhibits signaling cascades upstream of CD40 ligand transcription.J Immunol 172:2678-86.
Jordan MB, Hildeman D, Kappler J, Marrack P. (2004) An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+ T cells and interferon gamma are essential for the disorder.Blood 104:735-43.
Ivanovska I, Galonek HL, Hildeman DA, Hardwick JM. (2004) Regulation of cell death in the lymphoid system by Bcl-2 family proteins.Acta Haematol 111:42-55.

Professional Organization Memberships

American Association of Immunologists

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