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Warren D Shlomchik MD

Professor of Medicine (Hematology), of Immunobiology and of Medicine (Hematology)

Research Interests

Mechanisms of antigen presentation; T cell effector function; Regulation of Graft-vs.-Host Disease and Graft-vs.-Leukemia


Research Summary

Dr. Warren Shlomchik’s lab studies Graft-vs.-Host Disease (GVHD) and Graft-vs.-Leukemia (GVL) in murine models of allogeneic stem cell transplantation. T cells that accompany stem cell grafts are key players in alloSCT. They can mediate a potent anti-neoplastic effect by recognizing host malignant cells as non-self. They are also critical for reconstituting anti-infectious T cell immunity. However, as currently practiced, alloSCT has two key drawbacks. First, donor T cells can mount a global attack on normal host tissues such as skin, liver, and intestines in a process called Graft-vs.-Host Disease (GVHD). Because of GVHD, all patients receive some type of immunosuppression which reduces GVHD, but at the cost of decreased immune reconstitution and GVL. Second, many neoplasms such as blast crisis CML are resistant to GVL for reasons yet to be elucidated. Dr. Shlomchik’s lab uses murine models of GVHD and GVL to understand basic principles of antigen presentation, T cell activation, and T cell effector function with a goal of developing new therapeutic approaches to overcome these obstacles.

Extensive Research Description

Dr. Warren Shlomchik’s lab studies Graft-vs.-Host Disease (GVHD) and Graft-vs.-Leukemia (GVL) in murine models of allogeneic stem cell transplantation. T cells that accompany stem cell grafts are key players in alloSCT. They can mediate a potent anti-neoplastic effect by recognizing host malignant cells as non-self. They are also critical for reconstituting anti-infectious T cell immunity. However, as currently practiced, alloSCT has two key drawbacks. First, donor T cells can mount a global attack on normal host tissues such as skin, liver, and intestines in a process called Graft-vs.-Host Disease (GVHD). Because of GVHD, all patients receive some type of immunosuppression which reduces GVHD, but at the cost of decreased immune reconstitution and GVL. Second, many neoplasms such as blast crisis CML are resistant to GVL for reasons yet to be elucidated. Dr. Shlomchik’s lab uses murine models of GVHD and GVL to understand basic principles of antigen presentation, T cell activation, and T cell effector function with a goal of developing new therapeutic approaches to overcome these obstacles.


Selected Publications

  • Anderson, B.E., A.L. Tang, Y. Wang, M. Froicu, D. Rothstein, J.M. McNiff, A.J. Demetris, D.L. Farber, W.D. Shlomchik, and M.J. Shlomchik, Enhancing alloreactivity does not restore GVHD induction but augments skin graft rejection by CD4 effector memory T cells. European journal of immunology, 2011.
  • Juchem, K.W., B.E. Anderson, C. Zhang, J.M. McNiff, A.J. Demetris, D.L. Farber, A.J. Caton, W.D. Shlomchik, and M.J. Shlomchik, A repertoire-independent and cell intrinsic defect in murine GVHD induction by effector memory T cells. Blood, 2011.
  • Matte-Martone, C., S. Venkatesan, H.S. Tan, I. Athanasiadis, J. Chang, J. Pavisic, and W.D. Shlomchik, Graft-versus-Leukemia (GVL) against Mouse Blast-Crisis Chronic Myelogenous Leukemia (BC-CML) and Chronic-Phase Chronic Myelogenous Leukemia (CP-CML): Shared Mechanisms of T Cell Killing, but Programmed Death Ligands Render CP-CML and Not BC-CML GVL Resistant. Journal of immunology, 2011.
  • Li, H., C. Matte-Martone, H.S. Tan, S. Venkatesan, J. McNiff, A.J. Demetris, D. Jain, F. Lakkis, D. Rothstein, and W.D. Shlomchik, Graft-versus-Host Disease Is Independent of Innate Signaling Pathways Triggered by Pathogens in Host Hematopoietic Cells. J Immunol, 2011. 186(1): p. 230-41.
  • Li, H., D.H. Kaplan, C. Matte-Martone, H.S. Tan, S. Venkatesan, K. Johnson, A.J. Demetris, J. McNiff, M.J. Shlomchik, and W.D. Shlomchik, Langerhans cells are not required for graft-versus-host disease. Blood, 2011. 117(2): p. 697-707.
  • Zheng, H., C. Matte-Martone, D. Jain, J. McNiff, and W.D. Shlomchik, Central memory CD8+ T cells induce graft-versus-host disease and mediate graft-versus-leukemia. J Immunol, 2009. 182(10): p. 5938-48.
  • Matte-Martone, C., J. Liu, D. Jain, J. McNiff, and W.D. Shlomchik, CD8+ but not CD4+ T cells require cognate interactions with target tissues to mediate GVHD across only minor H antigens, whereas both CD4+ and CD8+ T cells require direct leukemic contact to mediate GVL. Blood, 2008. 111(7): p. 3884-92.
  • Shlomchik, W.D. (2007). Graft-versus-host disease. Nat. Rev. Immunol. 7:340-52.

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