Research Faculty

622 West 168th Street
Room 4-477
New York, NY 10032

Phone: 212-305-7226
Education and Training
M.D. 1963
Cornell University

Robert Winchester, M.D.
Professor of Pediatrics, Medicine and Pathology
Research Summary

Dr. Winchester has had a sustained interest in autoimmunity and autoimmune diseases. His laboratory is focused on understanding the genetic basis of susceptibility to autoimmune disease and the mechanisms responsible for triggering and mediating autoimmune injury.

His earlier studies defined the molecular importance of IgG rheumatoid factors in rheumatoid arthritis and other autoantibodies in various human autoimmune diseases. He also introduced the use of F(ab')2fragments into cell surface immunofluorescence. Moreover, Dr. Winchester was one of the first to identify human MHC class II molecules on B cells and monocytes and the first to show that they were expressed on human T cells as markers of activation. As importantly, his studies of the polymorphisms of MHC molecules have provided the basis of establishing the link between MHC genotype and susceptibility to multiple forms of autoimmunity. For example in the late 1980's Dr. Winchester and colleagues showed that susceptibility to rheumatoid arthritis was determined by sequences in the HLA-DR beta chain of MHC class II molecules, and formulated the shared MHC 'epitope' hypothesis. This hypothesis provides a molecular basis for susceptibility to rheumatoid arthritis, implicating a region on the MHC molecule that both binds a peptide side chain and interacts with the TCR. This key discovery has emphasized the importance of the modern means of HLA typing, which involves DNA sequencing of the MHC genes and the theoretical basis for the discovery of antigens that initiate autoimmune disease.
More recently, Dr. Winchester has coupled the DNA sequencing of the MHC genes with the analysis and high throughput DNA sequencing of human T cell receptor genes to permit molecular analysis of the cognitive T cell/peptide/MHC recognition events that underlie the role of the adaptive immune system in autoimmunity.

His laboratory is also interested in the role played in immunity and by the triggering of innate immune receptors present on CD8 T cells, that is relevant to entities as diverse as celiac disease, psoriatic arthritis and the maternal-infant transmission of HIV-1.

During the last several years Dr. Winchester's laboratory has joined forces with several other laboratories to advance understanding of problems in human autoimmune disease. One group of collaborative interactions is with the Dr. Chess and his colleagues within the Autoimmunity Center of Excellence. Another is with Dr. Bana Jabri on problems of celiac disease. A major collaboration exists with Prof. Oliver FitzGerald of Dublin using a large Irish cohort to study the genetic susceptibility and T cell repertoire in psoriatic arthritis.

Dr. Winchester's laboratory has had a longstanding interest in the molecular basis of the synovial lining hyperplasia that occurs in certain forms of arthitis and mediates cartilage and joint erosion. His laboratory did much to characterize the distinctive phenotype of cultured rheumatoid arthritis synoviocytes. His identification of a number of genes, including SDF-1 and SLIT-3 in these synoviocytes suggested that some synoviocytes, particularly those exhibiting a "dentritic" or "stellate" morphologys resembled the mesenchymal stem cells of bone marrow, and that the inappropriate expression of some of these transcripts was responsible for cartilage invasion. Currently microarray analysis and real-time PCR is being used to extend insight into the developmental stage of these synoviocytes using cloned cells.

Selected Publications

1. Minevich, G., Kuhn, L., Polistena, C., Nuara, J., Winchester, R., (2008). Description of two new HLA-C alleles in a black South African population. Tissue Antigens 71, 72-76.

2. Wu, H.D., Maurer, M.S., Friedman, R.A., Marboe, C.C., Ruiz-Vazquez, E.M., Ramakrishnan, R., Schwartz, A., Tilson, M.D., Stewart, A.S., Winchester, R., (2007). The lymphocytic infiltration in calcific aortic stenosis predominantly consists of clonally expanded T cells. J Immunol 178, 5329-5339.

3. Winchester, R., (2006). Reshaping Cinderella's slipper: the shared epitope hypothesis. Arthritis Res Ther 8, 109.

4. Peterson, K.S., Huang, J.F., Zhu, J., D'Agati, V., Liu, X., Miller, N., Erlander, M.G., Jackson, M.R., Winchester, R., (2004). Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli. J Clin Invest 113, 1722-1733.

5. Johnson, T.C., Diamond, B., Memeo, L., Negulescu, H., Hovhanissyan, Z., Verkarre, V., Rotterdam, H., Fasano, A., Caillat-Zucman, S., Grosdidier, E., Winchester, R., Cellier, C., Jabri, B., Green, P.H., (2004). Relationship of HLA-DQ8 and severity of celiac disease: comparison of New York and Parisian cohorts. Clin Gastroenterol Hepatol 2, 888-894.

6. Winchester, R., Jane Pitt1, Manhattan Charurat, Laurence S. Magder, Harald H. H. Goring, Alan Landay, Jennifer S. Read, William Shearer, Edward Handelsman, Katherine Luzuriaga, George V. Hillyer, William Blattner (2004) Mother-to-Child Transmission of HIV-1: Strong Association with Certain Maternal HLA-B Alleles Independent of Viral Load Implicates Innate Immune Mechanisms
The Journal of Acquired Immune Deficiency Syndromes. In press

7. Curran, S.A., FitzGerald, O.M., Costello, P.J., Selby, J.M., Kane, D.J., Bresnihan, B., and Winchester, R. (2004). Nucleotide sequencing of psoriatic arthritis tissue before and during methotrexate administration reveals a complex inflammatory T cell infiltrate with very few clones exhibiting features that suggest they drive the inflammatory process by recognizing autoantigens. J Immunol 172:1935-1944.

8. Jiang H, Curran S, Ruiz-Vazquez E, Liang B, Winchester R., Chess L. Regulatory CD8+ T cells fine-tune the myelin basic protein-reactive T cell receptor V beta repertoire during experimental autoimmune
encephalomyelitis. Proc Natl Acad Sci USA. (2003) Jul 8;100(14):8378-83.

9. Jabri, B., Selby, J.M., Negulescu, H., Lee, L., Roberts, A.I., Beavis, A., Lopez-Botet, M., Ebert, E.C., and Winchester, R.. (2002). TCR Specificity Dictates CD94/NKG2A Expression by Human CTL. Immunity 17:487-499.

10. Seki T, Selby J, Haupl T, Winchester R. Use of differential subtraction method to identify genes that characterize the phenotype of cultured rheumatoid arthritis synoviocytes. Arthritis Rheum. (1998) Aug;41(8):1356-64.

11. Chen Y, Winchester R., Korber B, Gagliano J, Bryson Y, Hutto C, Martin N, McSherry G, Petru A, Wara D, Ammann A. Influence of HLA alleles on the rate of progression of vertically transmitted HIV infection in children: association of several HLA-DR13 alleles with long-term survivorship and the potential association of HLA-A*2301 with rapid progression to AIDS. Long-Term Survivor Study. Hum Immunol. (1997) Jul;55(2):154-62.

Honors and Awards

Concillor, International Workshop on Human Leukocyte Differentiation Antigens

Lee C. Howley, Sr., Prize for Arthritis Research, Arthritis Foundation for "Discovering the molecular basis of susceptibility to rheumatoid arthritis"

Fellow of the American Association for the Advancement of Science, for "Discovery of human class II major histocompatibility complex (MHC) molecules and identification of shared sequences in different MHC genes associated with rheumatoid arthritis."

Committees , Council, and Professional Society Memberships

Associate Editor, Journal of Clinical and Experimental Immunology

AIDS-Related Research-2

NIH Study Section: General Medicine A

American Society for Clinical Investigation

American Federation for Clinical Research

Association of American Physicians

American College of Rheumatology

American Association of Immunologists


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