Photo of Leslie E. Silberstein,  MD

Leslie E. Silberstein, MD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-2588
Fax: (617) 730-0765


leslie.silberstein@childrens.harvard.edu

Leslie E. Silberstein, MD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Professor, Pathology, Harvard Medical School
  • Director, Joint Program in Transfusion Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

In the bone marrow, hematopoietic stem and progenitor (HSPC) reside in close contact with stromal cells in distinct anatomical microenvironments, where they receive signals for retention as well as growth and maturation. A long-term objective of Dr. Silberstein’s research laboratory is to better define the role of specified bone marrow microenvironments in regulating HSPC development. To this end, the lab has developed novel quantitative imaging tools for 2D and 3D visualization of different bone marrow compartments including the distribution of both hematopoietic and non-hematopoietic cells, e.g. vascular and stromal cells. Complemented by molecular and cellular approaches, my goal is to understand how niche cells influence the dynamic nature of hematopoiesis in health and disease. On-going studies are focused on understanding how inflammatory signals modulate niche cells and concomitantly hematopoiesis. Ultimately, these studies may lead to opportunities for targeted therapeutic regeneration in various bone marrow disorders associated with cancer and acute and/or chronic inflammation.

Publications

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  • Ciuculescu MF, Park SY, Canty K, Mathieu R, Silberstein LE, Williams DA. Perivascular deletion of murine Rac reverses the ratio of marrow arterioles and sinusoids vessels and alters hematopoiesis in vivo. Blood 2015. PubMed
  • Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Sun Y, Zhu H, Chai L, Silberstein LE, Cheng T, Luo HR. Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis. Immunity 2015; 42:159-71. PubMed
  • Nombela-Arrieta C, Silberstein LE. The science behind the hypoxic niche of hematopoietic stem and progenitors. Hematology Am Soc Hematol Educ Program 2015; 2014:542-7. PubMed
  • Ueno S, Lu J, He J, Li A, Zhang X, Ritz J, Silberstein LE, Chai L. Aberrant expression of SALL4 in acute B cell lymphoblastic leukemia: Mechanism, function, and implication for a potential novel therapeutic target. Exp Hematol 2014; 42:307-316.e8. PubMed
  • Silberstein LE, Lin CP. A new image of the hematopoietic stem cell vascular niche. Cell Stem Cell 2013; 13:514-6. PubMed
  • Liang OD, Lu J, Nombela-Arrieta C, Zhong J, Zhao L, Pivarnik G, Mondal S, Chai L, Silberstein LE, Luo HR. Deficiency of lipid phosphatase SHIP enables long-term reconstitution of hematopoietic inductive bone marrow microenvironment. Dev Cell 2013; 25:333-49. PubMed
  • Nombela-Arrieta C, Pivarnik G, Winkel B, Canty KJ, Harley B, Mahoney JE, Park SY, Lu J, Protopopov A, Silberstein LE. Quantitative imaging of haematopoietic stem and progenitor cell localization and hypoxic status in the bone marrow microenvironment. Nat Cell Biol 2013; 15:533-43. PubMed
  • Staber PB, Zhang P, Ye M, Welner RS, Nombela-Arrieta C, Bach C, Kerenyi M, Bartholdy BA, Zhang H, Alberich-Jordà M, Lee S, Yang H, Ng F, Zhang J, Leddin M, Silberstein LE, Hoefler G, Orkin SH, Göttgens B, Rosenbauer F, Huang G, Tenen DG. Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell 2013; 49:934-46. PubMed
  • Amabile G, Welner RS, Nombela-Arrieta C, D'Alise AM, Di Ruscio A, Ebralidze AK, Kraytsberg Y, Ye M, Kocher O, Neuberg DS, Khrapko K, Silberstein LE, Tenen DG. In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood 2013; 121:1255-64. PubMed
  • Park SY, Wolfram P, Canty K, Harley B, Nombela-Arrieta C, Pivarnik G, Manis J, Beggs HE, Silberstein LE. Focal adhesion kinase regulates the localization and retention of pro-B cells in bone marrow microenvironments. J Immunol 2013; 190:1094-102. PubMed
  • Gao H, Wu X, Sun Y, Zhou S, Silberstein LE, Zhu Z. Suppression of homeobox transcription factor VentX promotes expansion of human hematopoietic stem/multipotent progenitor cells. J Biol Chem 2012; 287:29979-87. PubMed
  • Jo H, Lo PK, Li Y, Loison F, Green S, Wang J, Silberstein LE, Ye K, Chen H, Luo HR. Deactivation of Akt by a small molecule inhibitor targeting pleckstrin homology domain and facilitating Akt ubiquitination. Proc Natl Acad Sci U S A 2011. PubMed
  • Nombela-Arrieta C, Ritz J, Silberstein LE. The elusive nature and function of mesenchymal stem cells. Nat Rev Mol Cell Biol 2011; 12:126-31. PubMed
  • Yu H, Li Y, Gao C, Fabien L, Jia Y, Lu J, Silberstein LE, Pinkus GS, Ye K, Chai L, Luo HR. Relevant mouse model for human monocytic leukemia through Cre/lox-controlled myeloid-specific deletion of PTEN. Leukemia 2010; 24:1077-80. PubMed
  • Jo H, Loison F, Hattori H, Silberstein LE, Yu H, Luo HR. Natural product Celastrol destabilizes tubulin heterodimer and facilitates mitotic cell death triggered by microtubule-targeting anti-cancer drugs. PLoS ONE 2010; 5:e10318. PubMed
  • 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 Res 2010; 70:202-11. PubMed
  • Kasorn A, Alcaide P, Jia Y, Subramanian KK, Sarraj B, Li Y, Loison F, Hattori H, Silberstein LE, Luscinskas WF, Luo HR. Focal adhesion kinase regulates pathogen-killing capability and life span of neutrophils via mediating both adhesion-dependent and -independent cellular signals. J Immunol 2009; 183:1032-43. PubMed
  • Sarraj B,Massberg S,Li Y,Kasorn A,Subramanian K,Loison F,Silberstein LE,von Andrian U,Luo HR. Myeloid-specific deletion of tumor suppressor PTEN augments neutrophil transendothelial migration during inflammation. J Immunol 2009; 182:7190-200. PubMed
  • Le Y,Xu L,Lu J,Fang J,Nardi V,Chai L,Silberstein LE. FAK silencing inhibits leukemogenesis in BCR/ABL-transformed hematopoietic cells. Am J Hematol 2009; 84:273-8. PubMed
  • Lu J,Jeong H,Kong N,Yang Y,Carroll J,Luo HR,Silberstein LE,Yupoma,Chai L. Stem cell factor SALL4 represses the transcriptions of PTEN and SALL1 through an epigenetic repressor complex. PLoS ONE 2009; 4:e5577. PubMed
  • Jia Y, Loison F, Hattori H, Li Y, Erneux C, Park SY, Gao C, Chai L, Silberstein LE, Schurmans S, Luo HR. Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of myelopoiesis. Proc Natl Acad Sci U S A 2008; 105:4739-44. PubMed
  • 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; 27:811-23. PubMed
  • 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; 21:1723-32. PubMed
  • Yang J, Chai L, Liu F, Fink LM, Lin P, Silberstein LE, Amin HM, Ward DC, Ma Y. Bmi-1 is a target gene for SALL4 in hematopoietic and leukemic cells. Proc Natl Acad Sci U S A 2007; 104:10494-9. PubMed
  • Babic AM, Josefsson EC, Bergmeier W, Wagner DD, Kaufman RM, Silberstein LE, Stossel TP, Hartwig JH, Hoffmeister KM. In vitro function and phagocytosis of galactosylated platelet concentrates after long-term refrigeration. Transfusion 2007; 47:442-51. PubMed
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