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Department
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Laboratory Medicine
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Hospital Title
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Senior Associate in Medicine
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Academic Title
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Professor of Pathology
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Phone
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617-919-2588
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Fax
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617-730-0765
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Email
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Leslie Silberstein
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Location
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Karp Family Research Building
10th Floor, Room 10217
1 Blackfan Circle
Boston MA 02115
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The overall theme of Dr. Silberstein's laboratory is to understand the mechanisms by which niche-specific signals in the bone marrow microenvironment influence hematopoiesis.
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Both the localization and migration between bone marrow niches of hematopoietic progenitor cells depend on cell-cell and cell matrix interactions, which result from the cooperation of cytokine receptors, chemokine receptors, and adhesion molecules. Using B lineage differentiating bone marrow cells as a model, the laboratory wishes to define the molecular signaling pathways of the CXCL12/CXCR4 chemokine axis. Although this axis appears to play a major role in hematopoietic progenitor homing/engraftment in the bone marrow as well as retention in the bone marrow for normal hematopoietic development, the mechanisms by which these processes occur remain largely unknown.
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By better understanding the molecular signaling pathways of the CXCL12/CXCR4 axis, the laboratory hopes to devise strategies to improve stem/progenitor cell engraftment following transplant. Laboratory methods include both molecular and cellular approaches of human and murine cells and use of gene targeted animal models. A major focus of the laboratory is the use of laser scanning cytometry to spatially analyze hematopoietic stem and progenitor cells in the bone marrow.
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Dr. Silberstein received his Baccalaureate and M.D. Degrees from the University of Leiden, the Netherlands, and completed his post-doctoral training in Hematology/Oncology and Transfusion Medicine at Tufts-New England Medical Center in Boston, MA. He is currently a Professor of Pathology at Harvard Medical School and the Director of the Joint Program in Transfusion Medicine at Children's Hospital Boston, Brigham and Women's Hospital, and the Dana-Farber Cancer Institute. He is also a Senior Investigator and Director of the Center for Human Cell Therapy at the CBR Institute for Biomedical Research.
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- Glodek AM, Honczarenko M, Le Y, Campbell JJ, Silberstein LE. Sustained activation of cell adhesion is a differentially regulated process in B lymphopoiesis. Journal of Experimental Medicine, 197:4, 1-14. 2003
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- 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. 1;174(5):2582-90. 2005.
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- 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, 22(2):259-270. 2005
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- 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.
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