Deborah Lewinsohn, M.D.

Biography
After receiving her B.S. in biology from Yale University, Deborah Lewinsohn attended Stanford University School of Medicine and received her M.D. in 1989. Dr. Lewinsohn was a Fellow of Pediatric Infectious Diseases at the University of Washington, Seattle, WA, from 1993-1996 and an Associate in Clinical Resarch in the Immunology Program at the Fred Hutchinson Cancer Research Center 1993-1998. At present, she is adjunct Assistant Professor at the OHSU Department of Molecular Microbiology and Immunology, an Assistant Professor in Infectious Disease in the Pediatrics Department of OHSU, affiliate Assistant Scientist at the Division of Pathobiology and Immunology, Oregon Regional Primate Research Center, OHSU, Portland, OR, and an assistant scientist at the Vaccine and Gene Therapy Institute.

Research Overview

In humans and in animal models, the induction and maintenance of virus-specific CD8+ T cell responses is essential for the control of persistent viral infections, such as cytomegalovirus (CMV), Epstein Barr virus (EBV), and human immunodeficiency virus (HIV). Primary HIV infection induces strong HIV-specific CTL responses directed towards several viral proteins that contribute to the resolution of viremia and the maintenance of clinical latency. However, the HIV-specific CTL responses elicited are unable to completely curtail virus replication and are lost with progression to AIDS. This failure to control HIV infection despite the strength and breadth of the CTL response may reflect the loss of HIV-specific CD4+ T helper cells needed to support CD8+ CTL. In addition, virus may evade recognition by CTL by mutation of CTL epitopes or by HIV Nef-mediated down-regulation of cell surface expression of MHC Class I. One focus of my laboratory is to investigate these and other possible mechanisms mediating loss of viral control in infected individuals.

A second focus of the laboratory is on HIV vaccine development. The World Health Organization estimates that over 6 million people per year, including over 600,000 children per year, acquire HIV infection. While highly active anti-retroviral therapy (HAART) has reduced the morbidity and mortality of HIV infection in the short term, it remains unavailable to much of the world and is not curative. Therefore, an effective HIV vaccine is urgently needed and one important target group for HIV vaccines is breastfeeding infants of HIV-infected women. Insights gained from studies of the immunobiology of HIV suggest that an effective HIV vaccine will need to induce strong CD8+ T cell responses, CD4+ T cell responses, and neutralizing antibodies.
Another major focus of the laboratory is to develop a model for HIV vaccine development for infants using the SIV/rhesus macaque model. A study is in progress, comparing the immunogenicity and efficacy of an SIV vaccine candidate in infant versus juvenile Rhesus macaques. The overall goal of this work is to identify vaccine strategies that will induce durable T and B cell immunity in and provide protection for infants. Secondly, we are studying HIV-specific T cell responses in HIV-infected children on HAART. We have found that children, in contrast to adults, maintain strong HIV-specific CD8+ T cell responses as long as two years on therapy, while adults on HAART quickly lose CD8+ T cell responses. These results suggest that immune reconstitution on HAART differs in children compared to adults and have important implications for clinical care of HIV-infected children and the design of strategies to augment HIV immunity in infected individuals on HAART.

Selected References

Cooper, L.J.N., Kalos, M., Lewinsohn, D.A., Riddell, S.R., and Greenberg, P.D. (2000) Transfer of specificity for human immunodeficiency virus type 1 into primary human T lymphocytes by introduction of T cell receptor genes. Journal of Virology, 74(17): 8207-12.

Brodie, S.J., Patterson, B.K., Lewinsohn D.A., Greenberg, P.D., Riddell, S.R., and Corey, L. (2000) HIV-specific cytotoxic T lymphocytes traffic to lymph nodes and localize at sites of HIV replication and cell death. Journal of Clinical Investigation, 105(10): 1407-17.

McKinney D.M., Lewinsohn, D.A., Riddell, S.R., Greenberg, P.D., and Mosier, D. (1999) Antiviral activity of HIV-specific CD8+ CTL clones is limited by elimination due to encounter with HIV-infected targets, Journal of Immunology, 163(2):861-7.

Brodie, S.J., Lewinsohn, D.A., Patterson, B.K., Jiyamapa, D., Corey, L., Greenberg, P.D., and Riddell, S.R. (1999) In vivo migration and function of transferred HIV-1 specific cytotoxic T cells. Nature Medicine, 5(1), 34-41.

Riddell, S.R., Elliott, M., Lewinsohn, D.A., Gilbert, M.J., Wilson, L., Manley, S.A., Lupton, S.D., Overell, R.W., Reynolds, T.C., Corey, L., and Greenberg, P.D. (1996). T Cell mediated rejection of gene-modified HIV-specific cytotoxic T lymphocytes in HIV-infected patients. Nature Medicine, 2, 216-23.

A more complete listing of publications by Dr. Lewinsohn is available from the National Library of Medicine [PubMed]

 

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