Research Topics
Genomes and Genes | REUBEN JAMES SHAWSummaryAffiliation: The Salk Institute Country: USA Publications
Research Grants
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Publications
DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATMNorvin Fernandes
Department of Radiation Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
J Biol Chem 280:15158-64. 2005..Furthermore, this domain of ATM is required for ATM to form nuclear foci following exposure to ionizing radiation...
Raptor swoops in on metabolismReuben J Shaw
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Cell Metab 8:343-4. 2008..In this issue, two reports utilizing tissue-specific knockout mice detail key roles for mTORC1 in skeletal muscle and adipose tissue function...
LKB1: cancer, polarity, metabolism, and now fertilityReuben J Shaw
Dulbecco Center for Cancer Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Biochem J 416:e1-3. 2008..Male mice lacking the LKB1(s) isoform have dramatic defects in spermatozoa, resulting in sterility...- LKB1 and AMP-activated protein kinase control of mTOR signalling and growthR J Shaw
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Acta Physiol (Oxf) 196:65-80. 2009..These findings have broad implications for the control of cell growth by nutrients in a number of cellular and organismal contexts... - Glucose metabolism and cancerReuben J Shaw
Dulbecco Center for Cancer Research, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Curr Opin Cell Biol 18:598-608. 2006..Several promising therapeutic strategies based on modulation of AMPK, HIF and other metabolic targets have been proposed to exploit the addiction of tumor cells to increased glucose uptake and glycolysis... - Ras, PI(3)K and mTOR signalling controls tumour cell growthReuben J Shaw
Dulbecco Laboratory for Cancer Research, The Salk Institute, 10010 N Torrey Pines Road, La Jolla, California 9203, USA
Nature 441:424-30. 2006..The preponderance of mutations in these interconnected pathways suggests that the loss of growth-control checkpoints and promotion of cell survival in nutrient-limited conditions may be an obligate event in tumorigenesis... - The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metforminReuben J Shaw
Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
Science 310:1642-6. 2005..Finally, we show that metformin, one of the most widely prescribed type 2 diabetes therapeutics, requires LKB1 in the liver to lower blood glucose levels... - Tumor suppression by LKB1: SIK-ness prevents metastasisReuben J Shaw
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Sci Signal 2:pe55. 2009..Reduced SIK1 expression is correlated with poor prognosis in two large human breast cancer data sets. These findings suggest that SIK1 is a key upstream regulator of p53-dependent anoikis that may be targeted in tumorigenesis... - Metabolism and cancer mix in MadridReuben J Shaw
Dulbecco Center for Cancer Research, Howard Hughes Medical Institute and Salk Institute for Biological Studies, La Jolla, California, USA
EMBO Rep 11:249-51. 2010..It confirmed that the outlines of the main pathways involved in coordinating nutrient uptake and metabolism with cell growth have begun to emerge... - mTOR signaling: RAG GTPases transmit the amino acid signalReuben J Shaw
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Trends Biochem Sci 33:565-8. 2008..Two recent complimentary studies provide compelling evidence that the Rag family of small GTPases is both necessary and sufficient to transmit a positive signal from amino acids to mTOR... - The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stressReuben J Shaw
Department of Systems Biology, Harvard Medical School, and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
Proc Natl Acad Sci U S A 101:3329-35. 2004..The role of LKB1/AMPK in the survival of a subset of genetically defined tumor cells may provide opportunities for cancer therapeutics... - Cardiac-specific deletion of LKB1 leads to hypertrophy and dysfunctionYasumasa Ikeda
Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 284:35839-49. 2009..Cardiac hypertrophy and dysfunction in LKB1-deficient hearts are associated with alterations in AMPK and mTOR/p70S6 kinase/eEF2 signaling and with a reduction in vascular endothelial growth factor expression and vessel rarefaction... - mTOR and HIF-1alpha-mediated tumor metabolism in an LKB1 mouse model of Peutz-Jeghers syndromeDavid B Shackelford
Dulbecco Center for Cancer Research, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 106:11137-42. 2009..These findings suggest a number of therapeutic modalities for the treatment and detection of hamartomas in PJS patients, and potential for the screening and treatment of the 30% of sporadic human lung cancers bearing LKB1 mutations... - The LKB1 tumor suppressor negatively regulates mTOR signalingReuben J Shaw
Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
Cancer Cell 6:91-9. 2004..These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome... - The LKB1-AMPK pathway: metabolism and growth control in tumour suppressionDavid B Shackelford
Dulbecco Center for Cancer Research, Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
Nat Rev Cancer 9:563-75. 2009..The connection of AMPK with several tumour suppressors suggests that therapeutic manipulation of this pathway using established diabetes drugs warrants further investigation in patients with cancer... - AMPK phosphorylation of raptor mediates a metabolic checkpointDana M Gwinn
Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Mol Cell 30:214-26. 2008..These findings uncover a conserved effector of AMPK that mediates its role as a metabolic checkpoint coordinating cell growth with energy status... - AMPK regulates the circadian clock by cryptochrome phosphorylation and degradationKatja A Lamia
Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037, USA
Science 326:437-40. 2009..Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs... - AMPK and PPARdelta agonists are exercise mimeticsVihang A Narkar
Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA
Cell 134:405-15. 2008..These results demonstrate that AMPK-PPARdelta pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise... - Raptor is phosphorylated by cdc2 during mitosisDana M Gwinn
Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, La Jolla, California, United States of America
PLoS ONE 5:e9197. 2010..As mTOR has been previously tied to mitotic control, we examined further how raptor may contribute to this process... - Resveratrol improves health and survival of mice on a high-calorie dietJoseph A Baur
Department of Pathology, Paul F Glenn Laboratories for the Biological Mechanisms of Aging, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
Nature 444:337-42. 2006..These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing... - LKB1 deficiency in Tie2-Cre-expressing cells impairs ischemia-induced angiogenesisKoji Ohashi
Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
J Biol Chem 285:22291-8. 2010..These observations suggest that the LKB1-AMPK signaling axis in endothelial cells is a positive regulator of the revascularization response to tissue ischemia... - Optimizing dietary restriction for genetic epistasis analysis and gene discovery in C. elegansWilliam Mair
Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, United States of America
PLoS ONE 4:e4535. 2009..1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity...
Research Grants
- Role of LKB1 and AMPK in Metformin and TZD Control of Glucose Metabolism in LiverREUBEN SHAW; Fiscal Year: 2007..These studies will better illuminate the mechanism of action of these two widely used type 2 diabetes modalities, as well as identifying many new targets for the development of future therapeutics. ..
- Role of LKB1 and AMPK in Metformin and TZD Control of Glucose Metabolism in LiverREUBEN JAMES SHAW; Fiscal Year: 2010..These studies will better illuminate the mechanism of action of these two widely used type 2 diabetes modalities, as well as identifying many new targets for the development of future therapeutics. ..