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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
      DepartmentMolecular, Cell and Cancer 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, and in 2015 he received the Research Scholar Award from the Leukemia and Lymphoma Society.

         

        Research

         

        Please vist our website at http://www.umassmed.edu/guertinlab/ for more information.

         

        Abnormal metabolism is a hallmark of obesity, diabetes, and cancer, which encompass some of today’s major medical challenges.   Lifestyle choices (e.g. dietary habits, exercise) and genetics strongly influence metabolic health, but how these factors integrate at the cellular and molecular level is not well understood.  The goal of our research is to understand mechanistically how cells sense and respond to nutritional cues, and how modifiable and non-modifiable risk factors such as over-nutrition and mutations cause metabolic diseases.   

        Type 2 diabetes in particular has become an alarming worldwide epidemic.  The greatest risk factor for type 2 diabetes is being overweight or obese, which is also linked to cardiovascular disease and certain cancers.   Global shifts to more sedentary lifestyles, excessive consumption of cheap calories from sugars and fat, and widespread urbanization have caused obesity rates to soar both in developed and developing countries.  This has brought adipose tissue, and its cellular unit—the adipocyte—to the research forefront in understanding and fighting this serious global challenge.  We are currently exploring mechanisms that regulate adipocyte development and function and how adipocytes communicate with other organs to control systemic metabolic health.

        We are also interested in understanding how signal transduction pathways and metabolism intersect both in normal cells and in cancer cells.   In particular, we have a long-standing interest in the insulin and mTOR signaling pathways.  The mTOR protein kinase is the common core subunit of two biochemically distinct multi-subunit complexes called mTOR complex 1 (mTORC1) and mTORC2.  mTOR signaling is tightly intertwined with insulin signaling and aberrant mTOR signaling is a hallmark of many diseases including diabetes, cardiovascular disease, and cancer.   The mTOR complexes have unique upstream inputs and downstream functions and we are currently investigating the unique functions of each complex in different types of adipocytes and cancer cells. 

           

         

         

         



        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. Tang Y, Wallace M, Sanchez-Gurmaches J, Hsiao WY, Li H, Lee PL, Vernia S, Metallo CM, Guertin DA. Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism. Nat Commun. 2016; 7:11365.
          View in: PubMed
        2. Lee PL, Tang Y, Li H, Guertin DA. Raptor/mTORC1 loss in adipocytes causes progressive lipodystrophy and fatty liver disease. Mol Metab. 2016 Jun; 5(6):422-32.
          View in: PubMed
        3. Sanchez-Gurmaches J, Hung CM, Guertin DA. Emerging Complexities in Adipocyte Origins and Identity. Trends Cell Biol. 2016 May; 26(5):313-26.
          View in: PubMed
        4. Hu YJ, Belaghzal H, Hsiao WY, Qi J, Bradner JE, Guertin DA, Sif S, Imbalzano AN. Transcriptional and post-transcriptional control of adipocyte differentiation by Jumonji domain-containing protein 6. Nucleic Acids Res. 2015 Sep 18; 43(16):7790-804.
          View in: PubMed
        5. Sanchez-Gurmaches J, Hsiao WY, Guertin DA. Highly selective in vivo labeling of subcutaneous white adipocyte precursors with Prx1-Cre. Stem Cell Reports. 2015 Apr 14; 4(4):541-50.
          View in: PubMed
        6. Sanchez-Gurmaches J, Guertin DA. mTORC1 gRABs the Golgi. Cancer Cell. 2014 Nov 10; 26(5):601-3.
          View in: PubMed
        7. 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
        8. Sanchez-Gurmaches J, Guertin DA. Adipocytes arise from multiple lineages that are heterogeneously and dynamically distributed. Nat Commun. 2014; 5:4099.
          View in: PubMed
        9. 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
        10. 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
        11. 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
        12. 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
        13. 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
        14. 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
        15. 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
        16. 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
        17. 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
        18. 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
        19. 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
        20. Sparks CA, Guertin DA. Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy. Oncogene. 2010 Jul 1; 29(26):3733-44.
          View in: PubMed
        21. Guertin DA, Sabatini DM. The pharmacology of mTOR inhibition. Sci Signal. 2009; 2(67):pe24.
          View in: PubMed
        22. 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
        23. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007 Jul; 12(1):9-22.
          View in: PubMed
        24. 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
        25. 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
        26. 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
        27. Guertin DA, Sabatini DM. An expanding role for mTOR in cancer. Trends Mol Med. 2005 Aug; 11(8):353-61.
          View in: PubMed
        28. 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
        29. 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
        30. 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
        31. 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
        32. 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
        33. Guertin DA, Trautmann S, McCollum D. Cytokinesis in eukaryotes. Microbiol Mol Biol Rev. 2002 Jun; 66(2):155-78.
          View in: PubMed
        34. Guertin DA, McCollum D. Interaction between the noncatalytic region of Sid1p kinase and Cdc14p is required for full catalytic activity and localization of Sid1p. J Biol Chem. 2001 Jul 27; 276(30):28185-9.
          View in: PubMed
        35. Guertin DA, Chang L, Irshad F, Gould KL, McCollum D. The role of the sid1p kinase and cdc14p in regulating the onset of cytokinesis in fission yeast. EMBO J. 2000 Apr 17; 19(8):1803-15.
          View in: PubMed
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