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    Rachel M Gerstein PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMicrobiology and Physiological Systems
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-5564
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentCancer Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentImmunology and Virology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMolecular Genetics and Microbiology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentTranslational Science

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentCenter for AIDS Research

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentUmass Memorial Cancer Center of Excellence

        Overview 
        Narrative

        Academic Background

        PhD, Brandeis University, 1991

        Developmental regulation of V(D)J recombination and B cell development.

        Rachel Gerstein, PhDMammals start generating B lymphocytes during fetal development and continue to do so throughout life. My lab is interested in what controls the initiation of antibody gene rearrangement during B cell development. In order to pin-point when progenitors have acquired the ability to rearrange antibody genes, we are using a novel retroviral substrate assay for V(D)J recombination, utilizing very bright mutants of Green fluorescent protein (GFP). In addition, the generation of two GFP mutants with distinct excitation optima allows for detection of two distinct GFP genes within single cells.1 V(D)J recombination and the activity of genes of interest (using GFP as a reporter of gene expression) can be detected as intracellular fluorescence and are measured simultaneously in the same cell population, at the single cell level. We are using this dual reporter system to ask what are the molecules and mechanisms controlling the developmental activation of V(D)J recombination. In addition, my lab studies the process of developmental committment to the B cell lineages, using 7-color flow cytometry on a state-of-the-art 3 laser FACS.

        1 Anderson, M.T., etal. Proc. Natl. Acad. Sci. 93:8508-8511.


        Bibliographic 
        selected publications
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        1. Ramkumar C, Kong Y, Trabucco SE, Gerstein RM, Zhang H. Smurf2 regulates hematopoietic stem cell self-renewal and aging. Aging Cell. 2014 Jun; 13(3):478-86.
          View in: PubMed
        2. Zook EC, Zhang S, Gerstein RM, Witte PL, Le PT. Enhancing T lineage production in aged mice: a novel function of foxn1 in the bone marrow niche. J Immunol. 2013 Dec 1; 191(11):5583-93.
          View in: PubMed
        3. Dowdy CR, Frederick D, Zaidi SK, Colby JL, Lian JB, van Wijnen AJ, Gerstein RM, Stein JL, Stein GS. A germline point mutation in Runx1 uncouples its role in definitive hematopoiesis from differentiation. Exp Hematol. 2013 Nov; 41(11):980-991.e1.
          View in: PubMed
        4. Selimyan R, Gerstein RM, Ivanova I, Precht P, Subrahmanyam R, Perlot T, Alt FW, Sen R. Localized DNA demethylation at recombination intermediates during immunoglobulin heavy chain gene assembly. PLoS Biol. 2013; 11(1):e1001475.
          View in: PubMed
        5. Ramkumar C, Gerstein RM, Zhang H. Serial transplantation of bone marrow to test self-renewal capacity of hematopoietic stem cells in vivo. Methods Mol Biol. 2013; 976:17-24.
          View in: PubMed
        6. Ramkumar C, Cui H, Kong Y, Jones SN, Gerstein RM, Zhang H. Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating ubiquitination and degradation of YY1. Nat Commun. 2013; 4:2598.
          View in: PubMed
        7. Ramkumar C, Kong Y, Cui H, Hao S, Jones SN, Gerstein RM, Zhang H. Smurf2 regulates the senescence response and suppresses tumorigenesis in mice. Cancer Res. 2012 Jun 1; 72(11):2714-9.
          View in: PubMed
        8. Tatarek J, Cullion K, Ashworth T, Gerstein R, Aster JC, Kelliher MA. Notch1 inhibition targets the leukemia-initiating cells in a Tal1/Lmo2 mouse model of T-ALL. Blood. 2011 Aug 11; 118(6):1579-90.
          View in: PubMed
        9. Guikema JE, Gerstein RM, Linehan EK, Cloherty EK, Evan-Browning E, Tsuchimoto D, Nakabeppu Y, Schrader CE. Apurinic/apyrimidinic endonuclease 2 is necessary for normal B cell development and recovery of lymphoid progenitors after chemotherapeutic challenge. J Immunol. 2011 Feb 15; 186(4):1943-50.
          View in: PubMed
        10. Priyadharshini B, Welsh RM, Greiner DL, Gerstein RM, Brehm MA. Maturation-dependent licensing of naive T cells for rapid TNF production. PLoS One. 2010; 5(11):e15038.
          View in: PubMed
        11. Castro I, Wright JA, Damdinsuren B, Hoek KL, Carlesso G, Shinners NP, Gerstein RM, Woodland RT, Sen R, Khan WN. B cell receptor-mediated sustained c-Rel activation facilitates late transitional B cell survival through control of B cell activating factor receptor and NF-kappaB2. J Immunol. 2009 Jun 15; 182(12):7729-37.
          View in: PubMed
        12. Gerstein RM. Deciding the decider: Mef2c in hematopoiesis. Nat Immunol. 2009 Mar; 10(3):235-6.
          View in: PubMed
        13. Coles AH, Marfella CG, Imbalzano AN, Steinman HA, Garlick DS, Gerstein RM, Jones SN. p37Ing1b regulates B-cell proliferation and cooperates with p53 to suppress diffuse large B-cell lymphomagenesis. Cancer Res. 2008 Nov 1; 68(21):8705-14.
          View in: PubMed
        14. Li L, Dutra A, Pak E, Labrie JE, Gerstein RM, Pandolfi PP, Recht LD, Ross AH. EGFRvIII expression and PTEN loss synergistically induce chromosomal instability and glial tumors. Neuro Oncol. 2009 Feb; 11(1):9-21.
          View in: PubMed
        15. Malhotra S, Baba Y, Garrett KP, Staal FJ, Gerstein R, Kincade PW. Contrasting responses of lymphoid progenitors to canonical and noncanonical Wnt signals. J Immunol. 2008 Sep 15; 181(6):3955-64.
          View in: PubMed
        16. Pilbeam K, Basse P, Brossay L, Vujanovic N, Gerstein R, Vallejo AN, Borghesi L. The ontogeny and fate of NK cells marked by permanent DNA rearrangements. J Immunol. 2008 Feb 1; 180(3):1432-41.
          View in: PubMed
        17. Kuo YH, Gerstein RM, Castilla LH. Cbfbeta-SMMHC impairs differentiation of common lymphoid progenitors and reveals an essential role for RUNX in early B-cell development. Blood. 2008 Feb 1; 111(3):1543-51.
          View in: PubMed
        18. Hoek KL, Antony P, Lowe J, Shinners N, Sarmah B, Wente SR, Wang D, Gerstein RM, Khan WN. Transitional B cell fate is associated with developmental stage-specific regulation of diacylglycerol and calcium signaling upon B cell receptor engagement. J Immunol. 2006 Oct 15; 177(8):5405-13.
          View in: PubMed
        19. Harman BC, Miller JP, Nikbakht N, Gerstein R, Allman D. Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors. Blood. 2006 Aug 1; 108(3):878-85.
          View in: PubMed
        20. Borghesi L, Aites J, Nelson S, Lefterov P, James P, Gerstein R. E47 is required for V(D)J recombinase activity in common lymphoid progenitors. J Exp Med. 2005 Dec 19; 202(12):1669-77.
          View in: PubMed
        21. Labrie JE, Borghesi L, Gerstein RM. Bone marrow microenvironmental changes in aged mice compromise V(D)J recombinase activity and B cell generation. Semin Immunol. 2005 Oct; 17(5):347-55.
          View in: PubMed
        22. Alugupalli KR, Gerstein RM. Divide and conquer: division of labor by B-1 B cells. Immunity. 2005 Jul; 23(1):1-2.
          View in: PubMed
        23. Sambandam A, Maillard I, Zediak VP, Xu L, Gerstein RM, Aster JC, Pear WS, Bhandoola A. Notch signaling controls the generation and differentiation of early T lineage progenitors. Nat Immunol. 2005 Jul; 6(7):663-70.
          View in: PubMed
        24. Alugupalli KR, Leong JM, Woodland RT, Muramatsu M, Honjo T, Gerstein RM. B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity. 2004 Sep; 21(3):379-90.
          View in: PubMed
        25. Labrie JE, Sah AP, Allman DM, Cancro MP, Gerstein RM. Bone marrow microenvironmental changes underlie reduced RAG-mediated recombination and B cell generation in aged mice. J Exp Med. 2004 Aug 16; 200(4):411-23.
          View in: PubMed
        26. Borghesi L, Hsu LY, Miller JP, Anderson M, Herzenberg L, Herzenberg L, Schlissel MS, Allman D, Gerstein RM. B lineage-specific regulation of V(D)J recombinase activity is established in common lymphoid progenitors. J Exp Med. 2004 Feb 16; 199(4):491-502.
          View in: PubMed
        27. Borghesi L, Gerstein RM. Developmental separation of V(D)J recombinase expression and initiation of IgH recombination in B lineage progenitors in vivo. J Exp Med. 2004 Feb 16; 199(4):483-9.
          View in: PubMed
        28. Liang H, Chen Q, Coles AH, Anderson SJ, Pihan G, Bradley A, Gerstein R, Jurecic R, Jones SN. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue. Cancer Cell. 2003 Nov; 4(5):349-60.
          View in: PubMed
        29. Alugupalli KR, Gerstein RM, Chen J, Szomolanyi-Tsuda E, Woodland RT, Leong JM. The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytes. J Immunol. 2003 Apr 1; 170(7):3819-27.
          View in: PubMed
        30. Petro JB, Gerstein RM, Lowe J, Carter RS, Shinners N, Khan WN. Transitional type 1 and 2 B lymphocyte subsets are differentially responsive to antigen receptor signaling. J Biol Chem. 2002 Dec 13; 277(50):48009-19.
          View in: PubMed
        31. Miller JP, Izon D, DeMuth W, Gerstein R, Bhandoola A, Allman D. The earliest step in B lineage differentiation from common lymphoid progenitors is critically dependent upon interleukin 7. J Exp Med. 2002 Sep 2; 196(5):705-11.
          View in: PubMed
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