David A Guertin PhD
Title Assistant Professor
Institution University of Massachusetts Medical School
Department Program in Molecular Medicine
Address University of Massachusetts Medical School
373 Plantation Street
Worcester MA 01605
Telephone 508/856-8064
Email
Other Positions
Institution UMMS - School of Medicine
Department Cancer Biology

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

Institution UMMS - Graduate School of Biomedical Sciences
Department MD/PhD Program

Institution UMMS - Programs, Centers & Institutes
Department Diabetes and Endocrinology Research Center
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.

     

Signal Transduction in Development and Disease

We are interested in how signaling networks integrate information about
nutrient and energy availability with growth factors to control tissue
growth and how altered signaling circuitry contributes to human diseases
such as cancer, degenerative disorders, and diabetes. Currently, we focus
on a nutrient and growth factor sensing kinase called mTOR.

For more information about our research, please visit our website at
http://www.guertinlab.com/Site/Home.html

  

  

Figures

FIGURE 1

Figure 1

Figure 1.  The mTOR kinase forms at least two distinct complexes called mTORC1 and mTORC2.

Biochemical studies into the mechanism of how mTOR controls cell growth revealed that mTOR exists in at least two distinct complexes called mTORC1 and mTORC2.   In cells, the mTOR complexes serve as signal integration centers because their activity is influence by inputs from diverse sources.  Each complex contains numerous subunits, some common to both complexes, and others that are unique to either mTORC1 or mTORC2.  The unique subunits direct mTOR kinase activity towards specific substrates, including the 4E-BP1 protein, a regulator of protein synthesis, and the AGC-family kinases S6K, AKT, and SGK, which control many cellular processes including cell growth, proliferation, apoptosis, and ion transport.

 

FIGURE 2

Figure 2

Figure 2.  mTORC2 is required for prostate cancer induced by loss of the PTEN tumor suppressor. 

(A-C)  H&E stains of the prostate epithelium.  (A) Section of prostate epithelium from a wild-type mouse.  (B) Deletion of the PTEN tumor suppressor in the prostate epithelium leads to prostate cancer with short latency.  (C) Inactivation of mTORC2 blocks prostate cancer formation induced by PTEN loss.  (D-F) Sections are labeled with a phospho-specific antibody to the mTORC2 substrate Akt.  (D) Akt phosphorylation is low in a normal prostate epithelium.  (E) Akt phosphoryaltion is dramatically elevated in prostate epithelial cells when PTEN is deleted.  (F) Inactivation of mTORC2 blocks the hyperphosphorylation of Akt induced by PTEN loss.     

 

Publications
1. 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
 
2. 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
 
3. 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
 
4. 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
 
5. 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
 
6. 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
 
7. Guertin DA, Sabatini DM. The pharmacology of mTOR inhibition. Sci Signal. 2009; 2(67):pe24.
  View in: PubMed
 
8. 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
 
9. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007 Jul; 12(1):9-22.
  View in: PubMed
 
10. 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
 
11. 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
 
12. 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
 
13. Guertin DA, Sabatini DM. An expanding role for mTOR in cancer. Trends Mol Med. 2005 Aug; 11(8):353-61.
  View in: PubMed
 
14. 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
 
15. 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
 
16. 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
 
17. 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
 
18. 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
 
19. Guertin DA, Trautmann S, McCollum D. Cytokinesis in eukaryotes. Microbiol Mol Biol Rev. 2002 Jun; 66(2):155-78.
  View in: PubMed
 
20. 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
 
21. 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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Keyword
Last Name
Institution
    
 
 
 
Keywords   
Protein Kinases
Neoplasms
Cell Division
Protein-Serine-Threonine Kinases
Signal Transduction
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Co-Authors  
McCollum, Dannel
See all (1) people
Physical Neighbors  
Guilherme, Adilson
Pazour, Gregory
Van den Berg, Lambertus
Lifshitz, Lawrence
Furcinitti, Paul

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