Researcher’s Profile

Megan Sykes, MD

Director, Columbia Center for Translational Immunology
Quote: 

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

Overview: 

Our research has developed ways 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. 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. We pioneered xenogeneic thymic transplantation as an approach to tolerance induction. We have demonstrated that non-myeloablative induction of mixed chimerism reverses the autoimmunity of Type 1 diabetes. We have recently developed novel humanized mouse models allowing "personalized" analysis of immune disease pathogenesis and immunotherapy. Additionally, we have developed novel tools for the analysis of the human alloresponse and are using these tools to better understand organ transplant immunobiology and tolerance in patients.

Publications: 
Kalscheuer H, Danzl N, Onoe T, Faust T, Winchester R, Goland R, Greenberg E, Spitzer TR, Savage DG, Tahara H, Choi G, Yang YG, Sykes M. A model for personalized in vivo analysis of human immune respons
Kawai T, Sachs DH, Sykes M, Cosimi AB, for the Immune Tolerance Network. HLA mismatched renal transplantation without maintenance immunosuppression-an update. Letter to the Editor. May 9, 2013 N Engl J Med 2013; 368:1850-1852. PMID: 23656665 PMC3760499.
Kalscheuer H, Onoe T, Dahmani A, Holzl M, Yamada K, Sykes M. Xenograft tolerance and immune function of human T cells developing in pig thymus xenografts. Journal of Immunology, 2014 Apr 1;192(7):3442-50. doi: 10.4049/jimmunol.1302886. PMID: 24591363. PMC
Morris H, De Wolf S, Robins H, Sprangers B, Locascio S, Shonts B, Kawai T, Wong W, Yang S, Zuber J, Shen Y, Sykes M. Tracking donor-reactive T cells: evidence for clonal deletion in tolerant kidney transplant patients. (Note: accompanied by FOCUS Article
Zuber J, Rosen S, Shonts B, Sprangers B, Savage T, Richman S, Yang S, Lau S, DeWolf S, Vlad G, Zorn E, Wong W, Emond J, Martinez M, Kato T, Sykes, M. Macrochimerism in intestinal transplantation: association with lower rejection rates and multivisceral tr
About: 

Megan Sykes’ research career, during which she has published >400 papers and book chapters, has focused on hematopoietic cell transplantation, organ allograft tolerance induction, xenotransplantation tolerance and Type 1 diabetes. Dr. Sykes has developed novel strategies for achieving graft-versus-tumor effects without graft-versus-host disease following hematopoietic cell transplantation (HCT). She developed an approach that has been evaluated in clinical trials of non-myeloablative haploidentical HCT whose safety and efficacy allowed trials of HCT for the induction of organ allograft tolerance, allowing intentional achievement of tolerance in humans for the first time. Dr. Sykes has dissected the tolerance mechanisms and pioneered minimal conditioning approaches for using HCT to achieve allograft and xenograft tolerance. Her work on xenogeneic thymic transplantation for tolerance induction has led, for the first time, to long-term kidney xenograft survival in non-human primates. More recently, she has extended the HCT approach to the problem of reversing autoimmunity while replacing destroyed islets of Langerhans in Type 1 diabetes. She has developed novel “humanized mouse” models that allow personalized analysis of human immune disorders and therapies. Dr. Sykes is a Past President of the International Xenotransplantation Association, served as Vice President of TTS, has repeatedly served on TTS Council and is a member of the Institute of Medicine of the National Academies.

Dr. Sykes believes that a mechanistic understanding of manipulations used to achieve clinical goals is essential to the translation of these manipulations to the clinic. It is for this reason that she has consistently worked at the interface between basic science and clinical applications, and has been able to translate her research to new treatments for patients requiring bone marrow or organ transplants. In 2010, after 20 years at Massachusetts General Hospital and Harvard Medical School, Dr. Sykes moved to Columbia University to establish the Columbia Center for Translational Immunology (CCTI). The CCTI is a multidisciplinary research center whose scope includes transplantation (organ and bone marrow), autoimmune disease, tumor immunology, infectious immunity and basic immunology. Currently, the CCTI has a staff of >100 scientists and support staff, including 13 faculty members. Dr. Sykes' own laboratory program currently includes major projects in the area of xenograft tolerance induction in humanized mouse models; unique humanized mouse models for the analysis and treatment of autoimmune diseases, including Type 1 diabetes and rheumatoid arthritis (the “personalized immune” mouse); studies of lymphocyte turnover, chimerism and T cell trafficking in patients receiving intestinal and liver transplants; tracking of alloreactive T cells in human transplant recipients; and both pre-clinical and clinical studies of non-myeloablative hematopoietic cell transplantation for the induction of allograft tolerance.