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Room 17-112
622 West 168th St
New York, NY   10032

Phone: 212-304-5696
Fax: 646-426-0019

-Professor of Medicine and Surgery
Department of Microbiology & Immunology

Megan Sykes, MD
Director, Columbia Center for Translational Immunology, Columbia University College of Physicians and Surgeons

Research Summary
Our research is in the areas of hematopoietic cell transplantation, achievement of graft-versus-leukemia effects without GVHD, organ allograft tolerance induction and xenotransplantation.

Research Activities
My research program aims to utilize bone marrow transplantation as immunotherapy to achieve graft-versus-tumor effects while avoiding the common complication of such transplants, graft-versus-host disease. Our laboratory studies in this area have led to novel approaches that have been evaluated in clinical trials. Another major area has been to utilize bone marrow transplantation for the induction of transplantation tolerance, both to organs from the same species (allografts) and from other species (xenografts). Our laboratory has worked toward the development of clinically feasible, non-toxic methods of re-educating the T cell, B cell and NK cell components of the immune system to accept allografts and xenografts without requiring long-term immunosuppressive therapy. Our work has also extended into the area of xenogeneic thymic transplantation as an approach to tolerance induction, and into the mechanisms by which non-myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes.

Positions & Appointments
2010-Present Director, Columbia Center for Translational Immunology Columbia University College of Physicians and Surgeons New York, NY
2010-Present Michael J. Friedlander Professor of Medicine Columbia University New York, NY
2010-Present Professor of Surgical Sciences, Surgery Department Columbia University New York, NY
2010-Present Professor of Microbiology and Immunology Columbia University New York, NY
2010-Present Director of Research, Transplant Initiative New York-Presbyterian Hospital New York, NY

Education and Training
1976-1978 Undergraduate Honors Biology (no degree obtained, entered medical school after two years) University of Western Ontario, Ontario, Canada
1982 M.D. University of Toronto, Toronto, Canada
1982-1983 Intern in Medicine Montreal General Hospital, , Montreal, Canada
1983-1984 Resident II, Medicine Toronto General Hospital, Toronto, Canada
1984-1985 Resident III, Medicine Toronto Western Hospital, Toronto, Canada
1985-1989 Visiting Associate, Immunology Branch National Cancer Institute, NIH, Bethesda, MD
1989-1990 Senior Staff Fellow, Immunology Branch National Cancer Institute, NIH, Bethesda, MD

Selected Publications:
1. Zhao Y, Swenson K, Sergio JJ, Arn JS, Sachs DH, Sykes M (1996) Skin graft tolerance across a discordant xenogeneic barrier. Nature Medicine 2(11):1211-1216

2. Sykes M, Szot GL, Swenson KA, Pearson DA (1997) Induction of high levels of allogeneic hematopoietic reconstitution and donor-specific tolerance without myelosuppressive conditioning. Nature Medicine 3:783-787

3. Wekerle T, Sayegh MH, Hill J, Zhao Y, Chandraker A, Swenson KG, Zhao G, Sykes M (1998) Extrathymic T cell deletion and allogeneic stem cell engraftment induced with costimulatory blockade is followed by central T cell tolerance. Journal of Experimental Medicine 187:2037-2044

4. Ohdan H, Yang Y-G, Shimizu A, Swenson KG, Sykes M (1999) Mixed chimerism induced without lethal conditioning prevents T cell- and anti-Gal1,3Gal-mediated graft rejection. Journal of Clinical Investigation 104:281-290

5. Fudaba Y, Spitzer TR, Shaffer JM, Kawai T, Fehr T, Delmonico FL, Preffer FI, Tolkoff-Rubin, Dey BR, Saidman SL, Kraus A, Bonnefoix T, McAfee S, Power K, Kattelman K, Colvin RB, Sachs DH, Cosimi AB Sykes M (2006) Myeloma responses and tolerance following combined kidney and non-myeloablative marrow transplantation in vivo and in vitro analyses. American Journal of Transplantation 6:2121-2031

6. Chakraverty R, Cote D, Buchli J, Cotter P, Hsu R, Zhao G, Sachs T, Pitsilldes C, Bronson R, Means T, Lin C, Sykes M (2006) An inflammatory checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral tissues. Journal of Experimental Medicine 203(8):2021-2031

7. Kurtz, J, Ravel F, Vallot C, Der J. Sykes M (2009) CTLA-4 on alloreactive CD4 T cells interacts with recipient CD80/86 to promote tolerance. Blood 113:3475-3484

8. Fehr T, Lucas C, Kurtz J, Onoe T, Zhao G, Hogan T, Vallot C, Rao A and Sykes M (2010) A CD8 T cell-intrinsic role for the calcineurin-NFAT pathway for tolerance induction in vivo. Blood 115:1280-1287

9. Onoe T, Kalscheuer H, Chittenden M, Zhao G, Yang YG, Sykes M (2010) Homeostatic expansion and phenotypic conversion of human T cells depend on peripheral interactions with APCs. Journal of Immunology 184(12):6756-6765

10. Saito TI, Li H, Sykes M (2010) Invariant natural killer T cells are required for antitumor responses induced by host-versus-graft responses. Journal of Immunology 185(4):2099-2105

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