Leslie Silberstein, MD

Department	Laboratory Medicine
Hospital Title	Senior Associate in Medicine
Academic Title	Professor of Pathology
Phone	617-919-2588
Fax	617-730-0765
Email	Leslie Silberstein
Location	300 Longwood Avenue Enders Research Building 8th floor, Rm 807

Research Overview

A long-term objective of Dr. Silberstein’s research laboratory is to better define niche-induced signals and their intracellular pathways controlling HSPC development and function. In the bone marrow, hematopoietic stem and progenitor cells (HSPC) reside in close contact with stromal cells in distinct anatomical microenvironments, where they receive signals for lodgement/retention as well as growth and maturation. The approaches in the laboratory involve both human and murine (i.e. gene targeted) model systems along with imaging technology to better define the bone marrow cavity In-situ laser scanning cytometry is used to objectively quantitate the spatial distribution of hematopoietic stem and progenitor cells in bone marrow niches, while multi-photon intravital microscopy is used to define the dynamic behavior of HSPC and their adhesive interactions with specific niche cells. The research program is directly relevant to understanding the pathogenesis of normal and neoplastic hematopoietic disorders such as leukemia, myelodysplasia and immunodeficiency. Moreover, a better definition of the signaling pathways regulating HSPC cell fate could lead to new translational approaches to enhance ex vivo expansion and improve transplantation efficiency of clinically relevant HSPC populations

About Leslie Silberstein

Dr. Silberstein received his Baccalaureate and M.D. Degrees from the University of Leiden, the Netherlands, and had post-graduate training in Hematology/Oncology and Transfusion Medicine at Tufts-New England Medical Center in Boston, MA. He then joined the staff at The University of Pennsylvania, where he worked from 1983-2000. During this time Dr. Silberstein established an academic transfusion medicine division with the Department of Pathology and Laboratory Medicine. He also served as Director of the Blood Bank and Transfusion Medicine Section, and Associate Director, Bone Marrow Transplant Program.

Dr. Silberstein was then recruited to Harvard, where he is a Professor of Pathology at Harvard Medical School and Director of the Joint Program in Transfusion Medicine at Children's Hospital Boston, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute. The Joint Program has three interrelated components: research, clinical and educational. An increasingly prominent activity within the Joint Program is the development of cell-based therapies. In addition, Dr. Silberstein is the Director of the Center for Human Cell Therapy (CHCT) at the Immune Disease Institute/Programs in Cellular and Molecular Medicine at Children's Hospital Boston (PICMM). The CHCT was established to provide an infrastructure to rapidly translate novel cell therapy protocols from the laboratory to the clinic. Anchored by its Translational Cell Therapy Laboratory and its Regulatory Core, the Center is designed to provide cell therapy resources for the Harvard community and its affiliated hospitals, from the technical level to the submission of Clinical Protocols and Investigational New Drug applications. He is also a Senior Investigator at the Immune Disease Institute/PICMM and Head of the Harvard Stem Cell Institute's Translational Research Program. Through both his leadership and research activities, he brings together Transfusion Medicine-related educational, research and clinical activities of the major Harvard Medical School affiliated institutions in Boston.

Key Publications

• Nombela-Arieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nature Review Cell Biology. 2011. Feb; 12(2):126-31.

• Gao H, Le Y, Wu X, Silberstein LE, Giese RW, Zhu Z. VentX, a novel lymphoid-enhancing factor/T-cell factor-associated transcription repressor, is a putative tumor suppressor. Cancer Research. 2010. 70 (1), 202-10.

• Le Y, Xu L, Lu J, Fang J, Nardi V, Chai L, Silberstein LE. FAK silencing inhibits leukemogenesis in BCR/ABL transformed hematopoietic cells. American Journal of Hematology. 2009. May; 84(5):273-8.

• Glodek AM, Le Y, Dykxhoorn DM, Park SY, Mostoslavsky G, Mulligan R, Lieberman J, Beggs HE, Honczarenko M, Silberstein LE. Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells. Leukemia. 2007. Aug;21(8):1723-32.

• Le Y, Zhu BM, Harley B, Park SY, Kobayashi T, Manis JP, Luo HR, Yoshimura A, Hennighausen L, Silberstein LE. SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway During B Lymphopoiesis. Immunity. 2007. Nov;27(5):811-23.

• Le Y, Honczarenko M, Glodek AM, Ho D, Silberstein LE. CXC chemokine ligand 12-induced focal adhesion kinase activation and segregation into membrane domain is modulated by regulator of G grotein signaling 1 in pro-B cells. Journal of Immunology. 2005. 1;174(5):2582-90. 

• Mazo IB, Honczarenko M, Leung H, Cavanagh LL, Bonasio R, Weninger W, Engelke K, Xia L, McEver RP, Koni PA, Silberstein LE, von Andrian UH. Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity. 2005. 22(2):259-270. 

• Glodek, Aleksandra M., Honczarenko, M., Le, Y., Campbell, J.J., Silberstein, L.E.  Sustained Activation of Cell Adhesion is a Differentially Regulated Process in B Lymphopoiesis.  Journal of Experimental Medicine. 2003. 197:4, 1-14.