Professor of Medicine and Immunology; Director, Hematopoietic Stem Cell Transplant and Cell Therapy; Scientific Director, Hematopoietic Malignancy Program, University of Pittsburgh Cancer Institute
BA, Harvard College; MD, University of Pennsylvania School of Medicine; Hematology-Oncology Fellowship, Hospital of the University of Pennsylvania
Understanding the complex immunology of allogeneic hematopoietic stem cell transplantation
Dr. Warren Shlomchik’s research program is dedicated to understanding the complex immunology of allogeneic hematopoietic stem cell transplantation (alloSCT), including graft-versus host disease (GVHD), graft-versus-leukemia (GVL) and immune reconstitution. The overall goal of Dr. Shlomchik’s studies is to make discoveries that can be translated in the clinic. One discovery was that memory phenotype T cells induce less GVHD than do naïve T cells and has been tested in a phase I/II clinical trial wherein patients received grafts depleted of naïve T cells. This approach is now being examined in a 4 arm clinical trial that includes high and lower intensity conditioning and grafts that are matched related and unrelated. At the bench, Dr. Shlomchik has mostly taken genetic approaches with mouse models to test fundamental hypotheses regarding alloSCT immunology. One major part of his research program has focused on mechanisms of GVHD: 1) roles of donor and host antigen presenting cells in priming alloreactive T cells; 2) mechanisms of antigen presentation; and 3) the role of donor tissue infiltrating APCs in promoting GVHD end organ damage. The second main area of investigation has been to understand mechanisms of GVL and GVL-resistance. Dr. Shlomchik’s lab has developed mouse models of GVL-sensitive chronic phase CML (CP-CML) and GVL-resistant blast crisis CML (BC-CML), with both leukemias induced by retroviral transfer of human oncogenes. This has provided both realistic models and genetic flexibility in that leukemias can be induced in any mouse, including those that are gene-modified. Recently, his lab has been applying two photon intravital microscopy to both GVHD and GVL.
Jinling (Julia) Liu, PhD
Faruk Sacirbegovic, PhD
Jieqing Zhu, PhD
Sarah Rossenberger (Technician)