Vuk Stambolic
PhD, University of Toronto
Research Synopsis
Signal Transduction and Cancer:Regulation of Cellular Proliferation, Survivaland Apoptosis
Cancer is a genetic disease. The ongoing discovery of genetic mutations in key components of signaling pathways in tumors underscores the importance of these molecular circuits to human cancer. As our ability to detect and assign genetic changes in patient material increases, so does the realization that the effective treatments based on these observations require highly specific therapeutic agents directed against the critical molecular drivers of tumor phenotypes. Genetic profiling of tumors is driving classification of cancers based on the genetic alterations they carry rather than their site of origin, aiming to define the criteria for the application of molecularly targeted treatments, a concept often called precision medicine.
Focusing on a signaling network named the PI3K signaling pathway, which is implicated in the majority of human malignancies, my laboratory aims to discover, characterize, and target the critical molecular nodes involved in cancer. Our particular interest is the biology of PTEN, a major tumor suppressor and one of the most frequently altered genes in human cancer. Utilizing biochemical, molecular biology and genetic approaches, as well as partnering with the experts in the areas of structural biology and protein turnover, our aim is a comprehensive mechanistic understanding of events governing tumorigenesis. Moreover, through collaborations with clinical oncologists and direct involvement in the correlative science components of several clinical trials, we are seeking to extend our mechanistic understanding of cancer pathways towards improving precision therapeutics approaches to cancer treatment.
Recent Publications
- C Bassi, J Ho, T Srikumar, R Dowling, C Gorrini, SJ Miller, TW Mak, BG Neel, B Raught, V Stambolic . Nuclear PTEN controls homologous recombination-mediated DNA repair and sensitivity to DNA damage Science 2013 Jul 26; 341(6144):395-9.
- Niraula S, Dowling RJO, Ennis M, Chang MC, Done SJ, Hood N, Escallon J, Leong WL, McCready D, Reedijk M, Stambolic V and Goodwin PJ. Metformin in Early Breast Cancer: A Prospective Window of Opportunity Neoadjuvant Study. Breast Cancer Research and Treatment, 2012 Oct; 135(3):821-30.
- Moniz L and Stambolic V. Nek10 mediates the G2/M cell cycle arrest and MEK auto-activation in response to UV irradiation – Mol Cell Biol. 2011 Jan;31(1):30-42.
- Maiuri T and Stambolic V. Regulation of Adipocyte Differentiation by Distinct Subcellular Pools of PKB/Akt J Biol Chem. 2010 May 14; 285(20):15038-47.
- Marshall CB, Ho J, Buerger C, Plevin MJ, Li GY, Li Z, Ikura M, Stambolic V. Characterization of intrinsic and TSC2 GAP-regulated GTPase activity of Rheb by real-time NMR Science Signaling . 2009 Jan 27; 2(55):ra3.
- Buerger C, Devries B, Stambolic V . Localization of Rheb to the endomembrane is critical for its signaling function.Biochem Biophys Res Commun. 2006 Jun 9;344(3):869-80.
Graduate Students
Ruhma Masud
Lauren Podmore