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    David A Guertin PhD

    TitleAssociate Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    373 Plantation Street
    Worcester MA 01605
    Phone508-856-8064
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentCancer Biology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentMD/PhD Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentDiabetes and Endocrinology Research Center

        Overview 
        Narrative

        Academic Background

        David A. Guertin received his B.S. in Biology from Saint Michael’s College in Vermont in 1997, and received his Ph.D. from the University of Massachusetts Medical School in 2002.  From 2002 to 2008 he conducted post-doctoral research at the Whitehead Institute for Biomedical Research in Cambridge MA with David Sabatini and support from the Damon Runyon Cancer Research Foundation and the Leukemia and Lymphoma Society.  In 2008 he became a Senior Research Associate with David Sabatini at the Whitehead Institute with support from the NIH/NCI Pathway to Independence Award.  He has been a member of the University of Massachusetts Medical School faculty since September 2009 in the Program in Molecular Medicine. In 2010, David Guertin was named a 2010 Pew Scholar in the Biomedical Sciences by the Pew Charitable Trusts.



        Mechanisms of Tissue Growth in Development and Disease

        We are interested in the mechanisms that regulatetissue growth and metabolism and their relevance to human diseases such ascancer, obesity, and diabetes.  There are basically 4 major building blocks(protein, carbohydrates, lipids, and nucleic acids) that must be both utilizedfor fuel and assembled into biomass in different compositions and amounts togenerate the vast array of cell and tissue types in the body.  We take a multidisciplinary approach, tryingto define the developmental paths that stem/progenitor cells follow to becoming a tissue and the signalsthat program metabolism and biomass production along the way.



        Pleasevisit our website at:
        http://www.guertinlab.com/Site/Home.html


        Figures

        Figure 1

        Figure1.  The mTOR pathway


        One specific area of interest is in elucidating the biochemical signals thatcontrol growth.  One particular growth regulator that interests us ismTOR, a protein kinase that assembles into at least two complexes.  mTORsenses intracellular nutritional state as well as systemic nutrients throughgrowth factor signaling pathways and uses this information to promote growth,proliferation, and survival.  We are interested in how mTOR does this andthe unique roles of each complex.

        A second area of interest is in defining developmental pathwaysthat give rise to important metabolic tissues, such as body fat.  Forexample, we recently discovered a mesodermal lineage that gives rise to some,but not all adipocytes.  The reason for this heterogeneity isunknown.  The developmental origins of adipocytes are still quitemysterious.  As obesity (a risk factor for diabetes, cardiovasculardisease, and cancer) has become a major medical challenge of this era,understanding adipocyte origins could help us fight this disease and itsassociated complications. 






         




         



        Rotation Projects

        We have several options for rotation projects in each of our interest areas.  Projects could include (1) studying mechanisms of how cells sense nutrients and growth factors and relay these signals to control tissue growth and metabolism; (2) studying stem/progenitor cells and the paths they take to becoming a tissue; or (3) how pathological changes to normal growth pathways cause human diseases such as cancer, obesity, and diabetes.  


        Interested students please stop bye!





        Post Docs

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



        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Hung CM, Calejman CM, Sanchez-Gurmaches J, Li H, Clish CB, Hettmer S, Wagers AJ, Guertin DA. Rictor/mTORC2 Loss in the Myf5 Lineage Reprograms Brown Fat Metabolism and Protects Mice against Obesity and Metabolic Disease. Cell Rep. 2014 Jul 10; 8(1):256-71.
          View in: PubMed
        2. Sanchez-Gurmaches J, Guertin DA. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun. 2014; 5:4099.
          View in: PubMed
        3. Yang K, Shrestha S, Zeng H, Karmaus PW, Neale G, Vogel P, Guertin DA, Lamb RF, Chi H. T Cell Exit from Quiescence and Differentiation into Th2 Cells Depend on Raptor-mTORC1-Mediated Metabolic Reprogramming. Immunity. 2013 Dec 12; 39(6):1043-56.
          View in: PubMed
        4. Sanchez-Gurmaches J, Guertin DA. Adipocyte lineages: Tracing back the origins of fat. Biochim Biophys Acta. 2014 Mar; 1842(3):340-51.
          View in: PubMed
        5. Hung CM, Garcia-Haro L, Sparks CA, Guertin DA. mTOR-dependent cell survival mechanisms. Cold Spring Harb Perspect Biol. 2012 Dec; 4(12).
          View in: PubMed
        6. Kalaitzidis D, Sykes SM, Wang Z, Punt N, Tang Y, Ragu C, Sinha AU, Lane SW, Souza AL, Clish CB, Anastasiou D, Gilliland DG, Scadden DT, Guertin DA, Armstrong SA. mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. Cell Stem Cell. 2012 Sep 7; 11(3):429-39.
          View in: PubMed
        7. Sanchez-Gurmaches J, Hung CM, Sparks CA, Tang Y, Li H, Guertin DA. PTEN loss in the Myf5 lineage redistributes body fat and reveals subsets of white adipocytes that arise from Myf5 precursors. Cell Metab. 2012 Sep 5; 16(3):348-62.
          View in: PubMed
        8. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012 Mar 30; 335(6076):1638-43.
          View in: PubMed
        9. Li H, Cotton JL, Guertin DA. Evaluating the therapeutic potential of mTOR inhibitors using mouse genetics. Methods Mol Biol. 2012; 821:329-47.
          View in: PubMed
        10. Hettmer S, Liu J, Miller CM, Lindsay MC, Sparks CA, Guertin DA, Bronson RT, Langenau DM, Wagers AJ. Sarcomas induced in discrete subsets of prospectively isolated skeletal muscle cells. Proc Natl Acad Sci U S A. 2011 Dec 13; 108(50):20002-7.
          View in: PubMed
        11. Wan M, Leavens KF, Saleh D, Easton RM, Guertin DA, Peterson TR, Kaestner KH, Sabatini DM, Birnbaum MJ. Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. Cell Metab. 2011 Oct 5; 14(4):516-27.
          View in: PubMed
        12. Peterson TR, Sengupta SS, Harris TE, Carmack AE, Kang SA, Balderas E, Guertin DA, Madden KL, Carpenter AE, Finck BN, Sabatini DM. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell. 2011 Aug 5; 146(3):408-20.
          View in: PubMed
        13. Lindquist RA, Ottina KA, Wheeler DB, Hsu PP, Thoreen CC, Guertin DA, Ali SM, Sengupta S, Shaul YD, Lamprecht MR, Madden KL, Papallo AR, Jones TR, Sabatini DM, Carpenter AE. Genome-scale RNAi on living-cell microarrays identifies novel regulators of Drosophila melanogaster TORC1-S6K pathway signaling. Genome Res. 2011 Mar; 21(3):433-46.
          View in: PubMed
        14. Guertin DA, Sabatini DM. The pharmacology of mTOR inhibition. Sci Signal. 2009; 2(67):pe24.
          View in: PubMed
        15. Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, Sheen JH, Mullholland DJ, Magnuson MA, Wu H, Sabatini DM. mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell. 2009 Feb 3; 15(2):148-59.
          View in: PubMed
        16. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007 Jul; 12(1):9-22.
          View in: PubMed
        17. Guertin DA, Stevens DM, Thoreen CC, Burds AA, Kalaany NY, Moffat J, Brown M, Fitzgerald KJ, Sabatini DM. Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1. Dev Cell. 2006 Dec; 11(6):859-71.
          View in: PubMed
        18. Carpenter AE, Jones TR, Lamprecht MR, Clarke C, Kang IH, Friman O, Guertin DA, Chang JH, Lindquist RA, Moffat J, Golland P, Sabatini DM. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome Biol. 2006; 7(10):R100.
          View in: PubMed
        19. Guertin DA, Guntur KV, Bell GW, Thoreen CC, Sabatini DM. Functional genomics identifies TOR-regulated genes that control growth and division. Curr Biol. 2006 May 23; 16(10):958-70.
          View in: PubMed
        20. Guertin DA, Sabatini DM. An expanding role for mTOR in cancer. Trends Mol Med. 2005 Aug; 11(8):353-61.
          View in: PubMed
        21. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science. 2005 Feb 18; 307(5712):1098-101.
          View in: PubMed
        22. Wheeler DB, Bailey SN, Guertin DA, Carpenter AE, Higgins CO, Sabatini DM. RNAi living-cell microarrays for loss-of-function screens in Drosophila melanogaster cells. Nat Methods. 2004 Nov; 1(2):127-32.
          View in: PubMed
        23. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004 Jul 27; 14(14):1296-302.
          View in: PubMed
        24. Hou MC, Guertin DA, McCollum D. Initiation of cytokinesis is controlled through multiple modes of regulation of the Sid2p-Mob1p kinase complex. Mol Cell Biol. 2004 Apr; 24(8):3262-76.
          View in: PubMed
        25. Guertin DA, Venkatram S, Gould KL, McCollum D. Dma1 prevents mitotic exit and cytokinesis by inhibiting the septation initiation network (SIN). Dev Cell. 2002 Dec; 3(6):779-90.
          View in: PubMed
        26. Guertin DA, Trautmann S, McCollum D. Cytokinesis in eukaryotes. Microbiol Mol Biol Rev. 2002 Jun; 66(2):155-78.
          View in: PubMed
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