Human genetic approaches to diseases of lymphocyte activation.
Our laboratory focuses on the study of the molecular regulation of T lymphocyte homeostasis, particularly as it relates to immunological tolerance, apoptosis, and autoimmune diseases. Through intense molecular research on the regulation of lymphocyte fate, the Fas receptor and other tumor necrosis factor receptors as well as their ligands have emerged as key regulators of T lymphocyte apoptosis. We are studying genetic abnormalities of this death pathway, particularly in the context of autoimmune lymphoproliferative syndrome (ALPS) and other non-ALPS conditions affecting lymphocyte homeostasis. These studies have led to further investigations of the regulation of the NF-kappaB signaling pathway, the molecular basis for programed cell death and viral cytopathicity, mechanisms of autoimmunity, and the regulation of mature T-cell tolerance. Our investigations promise to provide insight into the molecular mechanisms behind the regulation of immune response and contribute to the development of novel diagnostic and treatment methods for autoimmune diseases.
Prabhakar
Madhavi
M
Molecular Development of the Immune System Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases. National Institutes of Health, Building 10, Room 11N311, 10 Center Drive, MSC 1892, Bethesda, MD 20892-1892, USA.
Lenardo
Michael J
MJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D003588:Cytopathogenic Effect, Viral / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics* / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000145:classification / Q000235:genetics* / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D016328:NF-kappa B
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8953-8
17517660
J Biol Chem. 2007 Mar 9;282(10):7416-23
17213198
Science. 2000 Jun 30;288(5475):2351-4
10875917
J Virol. 2005 Apr;79(7):4025-32
15767404
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4952-7
16547133
Science. 2000 Jun 30;288(5475):2354-7
10875918
BMC Med Genet. 2007 Jul 02;8:41
17605793
J Cell Biol. 2004 Nov 22;167(4):735-44
15557123
Nat Immunol. 2007 Dec;8(12):1353-62
17982458
Science. 2005 Mar 4;307(5714):1465-8
15746428
Cell. 2007 Nov 30;131(5):927-39
18045535
Nat Med. 2005 Oct;11(10):1066-72
16170321
Biol Direct. 2008 Feb 27;3:6
18304352
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3369-74
16492778