Ashish Jain, M.D.Building 10, Room 5-395010 Center DriveBethesda, MD 20892-1456Phone: 301-594-5691Fax: email@example.com
Pam Edmonds, RNStudy CoordinatorBuilding 10, Room 12C103 10 Center DriveBethesda, MD 20892Phone: 301-435-7173 Fax: firstname.lastname@example.org
Ashish Jain received his medical degree from the State University of New York, Stony Brook, in 1992 and completed his training in internal medicine at the New England Medical Center, Boston. Subsequently, he was a fellow in the allergy and clinical immunology program at NIAID, and he completed postdoctoral training in the laboratory of Dr. Warren Strober. Dr. Jain joined the tenure track in 2002.
The Clinical Immunology Unit combines the study of inherited immune deficiency with basic scientific research to elucidate the molecular mechanisms underlying these disorders. Its ultimate goals are to improve diagnosis and treatments for patients. Specific diseases studied are the following:
We found that genetic alterations in NF-κB essential modulator (NEMO) cause ectodermal dysplasia with immune deficiency—a disorder characterized by absent or misshapen teeth, impaired development of sweat glands and hair follicles, and severe immune deficiency. NEMO is a regulatory component of the IKK complex and is central to the activation of NF-κB, a transcription factor that controls the expression of genes involved in immune responses, cellular development, and cancer. We wish to determine how various NEMO mutations influence IKK complex activation, expression of NF-κB regulated target genes, and development of clinical phenotypes in patients. Related efforts in the laboratory include making genetically altered mice with targeted mutations in signaling molecules, which regulate NF-κB.
Hyper IgM syndrome is characterized by hypogammaglobulinemia and is caused by several single-gene defects. In our studies of Hyper IgM syndromes, we have chosen patients with CD40 ligand deficiency for detailed investigation. We wish to understand the mechanism by which alterations in CD40 ligand cause the various phenotypes in patients. We are also undertaking novel preclinical and clinical investigations with the goal of developing successful targeted approaches to therapy for CD40 ligand deficiency.
Common variable immunodeficiency (CVID) is the most prevalent (1:25,000) symptomatic primary immunodeficiency in adults. CVID patients present with recurrent infections at mucosal tissues and are the consequence of marked hypogammaglobulinemia. The genetic basis of CVID is poorly understood. We have undertaken a genomics study of CVID, using high-throughput resequencing, to identify novel genetic changes in DNA samples from patients with CVID. Identifying disease susceptibility genes for CVID could enable more rapid diagnostic testing and eventually pave the way for better treatments of this increasingly common disorder.
Lopez-Granados E, Keenan JE, Kinney MC, Leo H, Jain N, Ma CA, Quinones R, Gelfand EW, Jain A. A novel mutation in NFKBIA/IKBA results in a degradation-resistant N-truncated protein and is associated with Ectodermal dysplasia with immunodeficiency. Hum Mutat. 2008 Jun;29(6):861-8.
Lopez-Granados E, Temmerman ST, Wu L, Reynolds JC, Follmann D, Liu S, Nelson DL, Rauch F, Jain A. Osteopenia in X-linked Hyper-IgM syndrome reveals a regulatory role for CD40 ligand in osteoclastogenesis. Proc Natl Acad Sci USA. 2007 Mar 20; 104(12):5056-61.
Temmerman ST, Ma CA, Borges L, Kubin M, Liu S, Derry JM, Jain A. Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination. Blood. 2006 Oct 1;108(7):2324-31.
Zhang J, Stirling B, Temmerman ST, Ma CA, Fuss IJ, Derry JM, Jain A. Impaired regulation of NF-kappaB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice. J Clin Invest. 2006 Nov;116(11):3042-9.
Jain A, Ma CA, Lopez-Granados E, Means G, Brady W, Orange JS, Liu S, Holland S, Derry JM. Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. J Clin Invest. 2004 Dec;114(11):1593-602.
Orange JS, Brodeur SR, Jain A, Bonilla FA, Schneider LC, Kretschmer R, Nurko S, Rasmussen WL, Köhler JR, Gellis SE, Ferguson BM, Strominger JL, Zonana J, Ramesh N, Ballas ZK, Geha RS. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest. 2002 Jun;109(11):1501-9.
Jain A, Ma CA, Liu S, Brown M, Cohen J, Strober W. Specific missense mutations in NEMO result in hyper-IgM syndrome with hypohydrotic ectodermal dysplasia. Nat Immunol. 2001 Mar;2(3):233-8.
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Last Updated May 21, 2010