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.

For a list of Dr. Stambolic's publications, please visit PubMed, Scopus or ORCID.

Associate Professor, Department of Medical Biophysics, University of Toronto‚Äč