Gerald T Nepom, M.D., Ph.D.

Dr. Nepom, Professor at Department  of Immunology, University of Washington School of Medicine, Director, Benaroya Institute, is an Advisory Committee Member for the JDRF Center (CCCT); he is a pioneer in the use of MHC-peptide tetramers in the detection and modification of autoimmune responses.

Dr. Nepom received his bachelors degree in Biochemistry from Harvard. He attended the University of Washington, receiving his Ph.D. in Biochemistry in 1977 and his M.D. in 1978. After post-doctoral work in immunogenetics in the Department of Pathology at Harvard Medical School, he returned to Seattle, joining the Fred Hutchinson Cancer Research Center and the University of Washington Medical School Faculty in 1982. Since 1985 he has been Member and Director of the Research Programs at the Benaroya Research Institute.

Ongoing projects in Dr. Nepom's laboratory are focused on identifying and understanding molecular and genetic mechanisms contributing to triggering of autoimmune disorders. The major clinical applications currently concern the role of HLA class II genes in the etiology of type I diabetes and adult and juvenile rheumatoid arthritis.
Experimental approaches toward these objectives include the analysis of the gene organization, structure, polymorphism and regulation of the HLA class II complex, with particular emphasis on individual alleles that are candidate disease susceptibility genes. Site-directed mutagenesis and retroviral-mediated expression systems are used to test specific molecular contributions to immune activation dependent on class II molecular recognition. The effect of structural polymorphisms on specific peptide binding is evaluated through a combination of binding, modeling and activation studies. DNA genotyping is used to identify novel HLA genes associated with disease, or linked to candidate susceptibility alleles, in diverse populations. HLA class II tetramers are used as novel probes of T cell specificity and function, both in model systems and in patients with autoimmune diseases, in conjunction with clinical trials of immunomodulatory drugs.