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.  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.  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.