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    Michael H Brodsky PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB-623
    Worcester MA 01605
    Phone508-856-1640
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentBioinformatics and Integrative Biology

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Gene Function and Expression

        Overview 
        Narrative

        Academic Background

        Michael Brodsky received his B.A. in Biochemistry from the University of California, Berkeley in 1989 and received his Ph.D. from the Massachusetts Institute of Technology in 1996. From 1996 to 2001, he was a post-doctoral fellow at the University of California, Berkeley where his work was supported by the American Cancer Society and the Howard Hughes Medical Institute. In 2001, Dr. Brodsky joined the faculty of the University of Massachusetts Medical School.

        Drosophila p53 and DNA Damage-Induced Apoptosis

        Michael Brodsky, Ph.D The overall goal of the lab is to understand how animal cells coordinate cell proliferation and cell death during development. To approach this problem, we are studying the regulation of apoptosis and cell cycle arrest following DNA damage in the fruit fly Drosophila melanogaster. In normal human cells, the p53 transcription factor helps regulate DNA damage-induced apoptosis, partly explaining why p53 is the most frequently mutated gene in human cancer cells. We have shown that a knockout of Drosophila p53 completely eliminates DNA damage-induced transcription and apoptosis (see figure), demonstrating that p53 function has been conserved from insects to mammals. By studying the function of fly p53, we hope to better understand how apoptosis is regulated during normal development and during tumor development.

        We are using a combination of genetics, microarrays, and informatics to identify and characterize new regulators and targets of Drosophila p53. Using Affymetrix microarrays, we have identified multiple transcriptional targets of Drosophila p53 including regulators of apoptosis such as reaper and cell-cell signaling molecules such as the Drosophila homolog of Tumor Necrosis Factor. Using genetic analysis, we have identified several genes required for DNA damage-induced apoptosis or cell cycle arrest. Characterization of these genes should provide new insights into how animal tissues respond to DNA damage. As we come to understand how p53 regulates the response to DNA damage, we will explore the mechanisms that determine why only a subset of cells exposed to DNA damage enter the apoptotic pathway and how developmental signals influence that decision.

        Drosophila p53 Regulates Irradiation-Induced Apoptosis

        Figure

        Drosophila p53 Regulates Irradiation-Induced Apoptosis

        Drosophila wing discs were treated with X-rays and stained for apoptotic cells (green dots). Damage-induced apoptosis is observed in wild type animals (A, B), but not in p53 mutant animals (C, D).

        A. Wild type, untreated.
        B. Wild type, + X-ray.
        C. p53 mutant, untreated.
        D. p53 mutant, + X-ray.



        Rotation Projects

        Potential Rotation Projects

        We are utilizing a variety of technologies to study p53 regulation and function in Drosophila. These include genetic screens, molecular biology, fluorescence and scanning electron microscopy, tissue culture, RNAi, homologous recombination, and others. Rotation projects in this lab will be determined based on a combination of the student's and PI's interests. Possible projects are listed below:

        Project 1: A genetic screen for new regulators of Drosophila p53.

        Project 2: Using RNAi and homologous recombination to study regulators of p53.

        Project 3: Characterization of p53 activation in Drosophila tissue culture cells by flurescence microscopy, Real-Time PCR, and RNAi.

        Project 4: Genetic analysis of Drosophila p53 targets identified in microarray experiments.



        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Brodsky for additional details.

        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Cheng Q, Kazemian M, Pham H, Blatti C, Celniker SE, Wolfe SA, Brodsky MH, Sinha S. Computational Identification of Diverse Mechanisms Underlying Transcription Factor-DNA Occupancy. PLoS Genet. 2013 Aug; 9(8):e1003571.
          View in: PubMed
        2. Enuameh MS, Asriyan Y, Richards A, Christensen RG, Hall VL, Kazemian M, Zhu C, Pham H, Cheng Q, Blatti C, Brasefield JA, Basciotta MD, Ou J, McNulty JC, Zhu LJ, Celniker SE, Sinha S, Stormo GD, Brodsky MH, Wolfe SA. Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. Genome Res. 2013 Jun; 23(6):928-40.
          View in: PubMed
        3. Christensen RG, Enuameh MS, Noyes MB, Brodsky MH, Wolfe SA, Stormo GD. Recognition models to predict DNA-binding specificities of homeodomain proteins. Bioinformatics. 2012 Jun 15; 28(12):i84-i89.
          View in: PubMed
        4. Andersen SL, Kuo HK, Savukoski D, Brodsky MH, Sekelsky J. Three Structure-Selective Endonucleases Are Essential in the Absence of BLM Helicase in Drosophila. PLoS Genet. 2011 Oct; 7(10):e1002315.
          View in: PubMed
        5. Kazemian M, Brodsky MH, Sinha S. Genome surveyor 2.0: cis-regulatory analysis in Drosophila. Nucleic Acids Res. 2011 Jul; 39 Suppl 2:W79-85.
          View in: PubMed
        6. Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS, Basciotta MD, Brasefield JA, Zhu C, Asriyan Y, Lapointe DS, Sinha S, Wolfe SA, Brodsky MH. FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res. 2011 Jan; 39(Database issue):D111-7.
          View in: PubMed
        7. Kazemian M, Blatti C, Richards A, McCutchan M, Wakabayashi-Ito N, Hammonds AS, Celniker SE, Kumar S, Wolfe SA, Brodsky MH, Sinha S. Quantitative analysis of the Drosophila segmentation regulatory network using pattern generating potentials. PLoS Biol. 2010; 8(8).
          View in: PubMed
        8. Guikema JE, Schrader CE, Brodsky MH, Linehan EK, Richards A, El Falaky N, Li DH, Sluss HK, Szomolanyi-Tsuda E, Stavnezer J. p53 represses class switch recombination to IgG2a through its antioxidant function. J Immunol. 2010 Jun 1; 184(11):6177-87.
          View in: PubMed
        9. McNamee LM, Brodsky MH. p53-independent apoptosis limits DNA damage-induced aneuploidy. Genetics. 2009 Jun; 182(2):423-35.
          View in: PubMed
        10. Noyes MB, Christensen RG, Wakabayashi A, Stormo GD, Brodsky MH, Wolfe SA. Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell. 2008 Jun 27; 133(7):1277-89.
          View in: PubMed
        11. Mauri F, McNamee LM, Lunardi A, Chiacchiera F, Del Sal G, Brodsky MH, Collavin L. Modification of Drosophila p53 by SUMO modulates its transactivation and pro-apoptotic functions. J Biol Chem. 2008 Jul 25; 283(30):20848-56.
          View in: PubMed
        12. Noyes MB, Meng X, Wakabayashi A, Sinha S, Brodsky MH, Wolfe SA. A systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Res. 2008 May; 36(8):2547-60.
          View in: PubMed
        13. Acharya JK, Dasgupta U, Rawat SS, Yuan C, Sanxaridis PD, Yonamine I, Karim P, Nagashima K, Brodsky MH, Tsunoda S, Acharya U. Cell-nonautonomous function of ceramidase in photoreceptor homeostasis. Neuron. 2008 Jan 10; 57(1):69-79.
          View in: PubMed
        14. Su VF, Jones KA, Brodsky M, The I. Quantitative analysis of Hedgehog gradient formation using an inducible expression system. BMC Dev Biol. 2007; 7:43.
          View in: PubMed
        15. Agin JR, Ziemer WA, Newman MC, Guilfoyle DE, Vought K, Ledenbach L, Brodsky MH, Hill W, Rice D, Ferreira JL, Werner BG, Martin BM, Shively R, Marrow T, Phillips RW, Wehling P, Labudde RA. Committee on microbiology and extraneous materials. J AOAC Int. 2006 Nov-Dec; 89(6):1700-1.
          View in: PubMed
        16. Oikemus SR, Queiroz-Machado J, Lai K, McGinnis N, Sunkel C, Brodsky MH. Epigenetic telomere protection by Drosophila DNA damage response pathways. PLoS Genet. 2006 May; 2(5):e71.
          View in: PubMed
        17. Meng X, Brodsky MH, Wolfe SA. A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat Biotechnol. 2005 Aug; 23(8):988-94.
          View in: PubMed
        18. Oikemus SR, McGinnis N, Queiroz-Machado J, Tukachinsky H, Takada S, Sunkel CE, Brodsky MH. Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 2004 Aug 1; 18(15):1850-61.
          View in: PubMed
        19. Brodsky MH, Weinert BT, Tsang G, Rong YS, McGinnis NM, Golic KG, Rio DC, Rubin GM. Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol Cell Biol. 2004 Feb; 24(3):1219-31.
          View in: PubMed
        20. Agin JR, Abbott DO, Ziemer WA, McClure FD, Ferreira JL, Ledenbach L, Hitchins AD, Hill W, Brodsky MH, Sciacchitano CJ, Guilfoyle DE, Loveys DA. Committee on Microbiology and Extraneous Materials. J AOAC Int. 2004 Jan-Feb; 87(1):321-9.
          View in: PubMed
        21. Abdu U, Brodsky M, Sch├╝pbach T. Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr Biol. 2002 Oct 1; 12(19):1645-51.
          View in: PubMed
        22. Rong YS, Titen SW, Xie HB, Golic MM, Bastiani M, Bandyopadhyay P, Olivera BM, Brodsky M, Rubin GM, Golic KG. Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 2002 Jun 15; 16(12):1568-81.
          View in: PubMed
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