Faculty
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Prabal Banerjee, Ph.D.
Research Scientist, Microbiology and Immunology
2216 Weiskotten Hall
Upstate Medical University
750 East Adams Street
Syracuse, NY 13210
(315) 464-7671
| Education and Clinical Training
MS: 2001, Devi Ahilya University, India, Microbiology
Ph.D.: 2007, SUNY Upstate Medical Center at Syracuse, NY
Research Abstract
Humanized SCID mouse models of hematopoiesis and cancer
Human T-lymphotropic virus type-1 (HTLV-1) is the etiologic agent of Adult T-cell leukemia, an aggressive mature CD4+/CD25+ T cell malignancy. We have previously demonstrated that HTLV-1 is capable of infecting human hematopoietic progenitor and stem cells (CD34+ HPCs) and that infection of CD34+ HPCs has dramatically different biological effects in comparison to infection of mature T lymphocytes. To determine if HTLV-1 infection of CD34+ HPC and HSCs recapitulates leukemogenesis in vivo, hematopoiesis in NOD/SCID mice was reconstituted by injection of HTLV-1-infected human CD34+ HPCs. Humanized NOD/SCID (NOD/SCID-hu) mice infected with HTLV-1 demonstrate persistent viral infection and viral gene expression was detected in mature human CD4+ (mature T cells), CD14+ (monocyte/macrophages), CD19+ (B cells) and CD34+ (hematopoietic progenitor/stem) cells in vivo. HTLV-1-infected SCID-hu mice developed T lymphoproliferative disease at ~8 weeks post-reconstitution and significantly elevated levels of HTLV-1 infected human CD4+ T cells in the thymus, mesenteric lymph node, spleen and peripheral blood was detected in these mice. Hyperproliferation of HTLV-1- infected CD34+ HPCs in the bone marrow suggests that hematopoietic stem cells represent viral reservoir target cells, which maintain HTLV-1 infection for, extended periods of time in vivo. Interestingly, we detected HTLV-1 proviral sequences in CD34+ HPC isolated from the peripheral blood of HTLV-1 seropositive patients. Thus, we speculate that HTLV-1 infection of hematopoietic stem cells may establish a virally-infected cancer stem cell, which gives rise to the monoclonal T cell malignancy in human ATL patients. HTLV infection of humanized NOD/SCID mice represents a novel in vivo model, which recapitulates viral leukemogenesis and provides a compelling model to investigate and characterize molecular events in human stem cells, which ultimately manifest in the development of ATL.
Selected references
Banerjee P, Sieburg M, Samuelson E, Feuer G
HTLV-1 Infection of CD34+ Hematopoietic Progenitor Cells Induces Cell Cycle Arrest by Modulation of p21cip1/waf1 and Survivin. Stem Cells. 2008 Sep 25
Banerjee P, Feuer G, Barker E.
Human T-cell leukemia virus type 1 (HTLV-1) p12I down-modulates ICAM-1 and -2 and reduces adherence of natural killer cells, thereby protecting HTLV-1-infected primary CD4+ T cells from autologous natural killer cell-mediated cytotoxicity despite the reduction of major histocompatibility complex class I molecules on infected cells. Journal of Virology. 2007 Sep;81(18):9707-17
Banerjee P, Rochford R, Antel J, Canute G, Wrzesinski S, Sieburg M, Feuer G.
Proinflammatory cytokine gene induction by human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2 Tax in primary human glial cells.Journal of Virology. 2007 Feb;81(4):1690-700
Tripp A, Banerjee P, Sieburg M, Planelles V, Li F, Feuer G.
Induction of cell cycle arrest by human T-cell lymphotropic virus type 1 Tax in hematopoietic progenitor (CD34+) cells: modulation of p21cip1/waf1 and p27kip1 expression. Journal of Virology. 2005 Nov;79(22):14069-78
Wu W, Vieira J, Fiore N, Banerjee P, Sieburg M, Rochford R, Harrington W Jr, Feuer G.
KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo. Blood. 2006 Jul 1;108(1):141-51
Publications - link to PubMed
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This profile was last updated on 04/03/2009
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