Rachel M Gerstein PHD
Title Associate Professor
Institution University of Massachusetts Medical School
Department Microbiology & Physiological Systems
Address University of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
Telephone 508-856-5564
Email
Other Positions
Institution UMMS - Graduate School of Biomedical Sciences
Department Immunology & Virology

Institution UMMS - Graduate School of Biomedical Sciences
Department Interdisciplinary Graduate Program

Institution UMMS - Graduate School of Biomedical Sciences
Department Molecular Genetics & Microbiology

Institution UMMS - Programs, Centers and Institutes
Department Center for AIDS Research

Institution UMMS - Programs, Centers and Institutes
Department Umass Memorial Cancer Center of Excellence
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.
Publications
1. 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 Jan; 11(1):e1001475.
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2. 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.
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3. 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.
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4. 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.
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5. 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.
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6. 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.
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7. 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.
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8. Gerstein RM. Deciding the decider: Mef2c in hematopoiesis. Nat Immunol. 2009 Mar; 10(3):235-6.
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9. 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.
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10. 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.
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11. 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.
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12. 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.
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13. 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.
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14. 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.
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15. 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.
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16. 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.
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17. 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.
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18. Alugupalli KR, Gerstein RM. Divide and conquer: division of labor by B-1 B cells. Immunity. 2005 Jul; 23(1):1-2.
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19. 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.
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20. 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.
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21. 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.
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22. 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.
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23. 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.
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24. 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.
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25. 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.
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26. 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.
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27. 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.
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28. Fischer GM, Solt LA, Hastings WD, Yang K, Gerstein RM, Nikolajczyk BS, Clarke SH, Rothstein TL. Splenic and peritoneal B-1 cells differ in terms of transcriptional and proliferative features that separate peritoneal B-1 from splenic B-2 cells. Cell Immunol. 2001 Oct 10; 213(1):62-71.
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29. Rothstein TL, Fischer GM, Tanguay DA, Pavlovic S, Colarusso TP, Gerstein RM, Clarke SH, Chiles TC. STAT3 activation, chemokine receptor expression, and cyclin-Cdk function in B-1 cells. Curr Top Microbiol Immunol. 2000; 252:121-30.
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30. Baird AM, Gerstein RM, Berg LJ. The role of cytokine receptor signaling in lymphocyte development. Curr Opin Immunol. 1999 Apr; 11(2):157-66.
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31. Anderson MT, Baumgarth N, Haugland RP, Gerstein RM, Tjioe T, Herzenberg LA, Herzenberg LA. Pairs of violet-light-excited fluorochromes for flow cytometric analysis. Cytometry. 1998 Dec 1; 33(4):435-44.
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32. Roederer M, De Rosa S, Gerstein R, Anderson M, Bigos M, Stovel R, Nozaki T, Parks D, Herzenberg L, Herzenberg L. 8 color, 10-parameter flow cytometry to elucidate complex leukocyte heterogeneity. Cytometry. 1997 Dec 1; 29(4):328-39.
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33. Khan WN, Alt FW, Gerstein RM, Malynn BA, Larsson I, Rathbun G, Davidson L, Müller S, Kantor AB, Herzenberg LA, et al. Defective B cell development and function in Btk-deficient mice. Immunity. 1995 Sep; 3(3):283-99.
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34. Lieber MR, Chang CP, Gallo M, Gauss G, Gerstein R, Islas A. The mechanism of V(D)J recombination: site-specificity, reaction fidelity and immunologic diversity. Semin Immunol. 1994 Jun; 6(3):143-53.
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35. Gerstein RM, Lieber MR. Coding end sequence can markedly affect the initiation of V(D)J recombination. Genes Dev. 1993 Jul; 7(7B):1459-69.
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36. Gerstein RM, Lieber MR. Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination. Nature. 1993 Jun 17; 363(6430):625-7.
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37. Sohn J, Gerstein RM, Hsieh CL, Lemer M, Selsing E. Somatic hypermutation of an immunoglobulin mu heavy chain transgene. J Exp Med. 1993 Feb 1; 177(2):493-504.
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38. Gerstein RM, Frankel WN, Hsieh CL, Durdik JM, Rath S, Coffin JM, Nisonoff A, Selsing E. Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes. Cell. 1990 Nov 2; 63(3):537-48.
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39. Rath S, Durdik J, Gerstein RM, Selsing E, Nisonoff A. Quantitative analysis of idiotypic mimicry and allelic exclusion in mice with a mu Ig transgene. J Immunol. 1989 Sep 15; 143(6):2074-80.
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40. Durdik J, Gerstein RM, Rath S, Robbins PF, Nisonoff A, Selsing E. Isotype switching by a microinjected mu immunoglobulin heavy chain gene in transgenic mice. Proc Natl Acad Sci U S A. 1989 Apr; 86(7):2346-50.
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41. Busto P, Gerstein R, Dupre L, Giorgetti CA, Selsing E, Press JL. Molecular analysis of heavy and light chains used by primary and secondary anti-(T,G)-A--L antibodies produced by normal and xid mice. J Immunol. 1987 Jul 15; 139(2):608-18.
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Keyword
Last Name
Institution
    
 
 
 
Keywords   
B-Lymphocytes
VDJ Recombinases
Lymphopoiesis
Hematopoietic Stem Cells
B-Lymphocyte Subsets
See all (230) keywords
Co-Authors  
Castilla, Lucio
Imbalzano, Anthony
Jones, Stephen
Ross, Alonzo
Woodland, Robert
See all (13) people
Physical Neighbors  
Akerley, Brian
Ikebe, Mitsuo
Baker, Richard
Zhuge, Ronghua
Wong, Sandy

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