Vuk Stambolic, PhD

Signal transduction and cancer: regulation of cellular proliferation, survival and apoptosis

Signal transduction is a cascade of molecular events orchestrated within individual cells in response to various stimuli. Cellular transformation, an early step in tumourigenesis, is almost exclusively caused by malfunction of signal transduction pathways. Immediate cellular environment including metabolic, mitogenic and positional clues, activity of various modifier genes, as well as selective pressure for tumour growth, profoundly affect cellular signalling throughput and play key roles in cancer initiation, progression and metastasis.

Our laboratory is interested in studying cancer-related signal transduction and its effects on cellular growth, survival and apoptosis. Our primary interest is the PI3K signalling pathway, which has been implicated in the etiology of multiple human malignancies. For instance, PI3K (PIK3A) is a potent oncogene whose mutations are often found in colon, breast, brain and lung cancers, whereas PTEN, a gene whose protein product directly counteracts PI3K activity, is one of the most frequently mutated tumour suppressor genes in a variety of human cancers.

Our previous research in this area included characterization of the physiological function of PTEN, as well as development of several animal model systems that were highly informative in characterizing the role of 3PI signalling in tumourigenesis and regulation of cell growth and size. More recently, we have become interested in the relevance of subcellular localization of pathway components as an additional regulatory input into 3PI signalling and have described the importance of compartmentalization of certain pathway components for proper signal propagation.

Focusing on the mechanistic relationship between key signalling molecules within the PI3K pathway, our current interests include examination of modes of PTEN regulation, prioritization of PKB/Akt substrates relevant to tumourigenesis and characterization of Rheb, a small GTPase and a downstream target of this pathway. Using proteomic and genomic approaches, as well as other modern molecular and cell biology techniques, our work aims to provide a thorough understanding of molecular mechanisms of signal transduction and may lead to the development of effective therapeutic strategies for treatment of cancer.

JNCI Cancer Spectr. 2018 Apr;2(2):pky028
Lohmann AE, Dowling RJO, Ennis M, Amir E, Elser C, Brezden-Masley C, Vandenberg T, Lee E, Fazaee K, Stambolic V, Goodwin PJ, Chang MC
Biol Psychiatry. 2017 May 03;:
Goiran T, Duplan E, Chami M, Bourgeois A, El Manaa W, Rouland L, Dunys J, Lauritzen I, You H, Stambolic V, Biféri MG, Barkats M, Pimplikar SW, Sergeant N, Colin M, Morais VA, Pardossi-Piquard R, Checler F, Alves da Costa C
Breast Cancer Res Treat. 2017 Apr 26;:
Lohmann AE, Liebman MF, Brien W, Parulekar WR, Gelmon KA, Shepherd LE, Ligibel JA, Hershman DL, Rastogi P, Mayer IA, Hobday TJ, Lemieux J, Thompson AM, Pritchard KI, Whelan TJ, Mukherjee SD, Chalchal HI, Bernstein V, Stambolic V, Chen BE, Goodwin PJ,...
J Clin Oncol. 2011 May 20;29(15_suppl):TPS103
Parulekar W, Chen BE, Elliott C, Shepherd LE, Gelmon KA, Pritchard KI, Whelan TJ, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, Rastogi P, Lemieux J, Ganz PA, Stambolic V, Goodwin PJ
Cell Death Dis. 2016 Dec 22;7(12):e2560
Ren Z, Aerts JL, Vandenplas H, Wang JA, Gorbenko O, Chen JP, Giron P, Heirman C, Goyvaerts C, Zacksenhaus E, Minden MD, Stambolic V, Breckpot K, De Grève J
J Clin Oncol. 2016 Dec 10;34(35):4249-4255
Lohmann AE, Goodwin PJ, Chlebowski RT, Pan K, Stambolic V, Dowling RJ
J Biol Chem. 2016 Oct 28;291(44):23364
Ruel L, Stambolic V, Ali A, Manoukian AS, Woodgett JR
Methods Mol Biol. 2016;1388:v
Salmena L, Stambolic V
Cell Metab. 2016 Apr 12;23(4):567-8
Dowling RJ, Lam S, Bassi C, Mouaaz S, Aman A, Kiyota T, Al-Awar R, Goodwin PJ, Stambolic V
Nat Commun. 2016;7:11127
Gandin V, Masvidal L, Cargnello M, Gyenis L, McLaughlan S, Cai Y, Tenkerian C, Morita M, Balanathan P, Jean-Jean O, Stambolic V, Trost M, Furic L, Larose L, Koromilas AE, Asano K, Litchfield D, Larsson O, Topisirovic I

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Associate Professor, Department of Medical Biophysics, University of Toronto​