B.Sc. University of British Columbia, 1988
Ph.D. University of British Columbia, 1996
Senior Research Scientist, Vancouver Prostate Centre
Assistant Professor, Department of Urologic Sciences, University of British Columbia
The primary focus of Dr. Ong's research program is to understand the molecular mechanisms that govern the progression of prostate cancer from a state of androgen sensitivity to hormone independence with the hope of developing novel therapeutic strategies to prevent or delay the progression of prostate cancer to androgen independence. His primary focus has been on the PTEN tumour suppressor gene, which is among the most frequently mutated genes in cancer. One or both copies of PTEN is mutated in over 70% of primary prostate cancer and PTEN is completely inactivated in over 50% of advanced prostate cancer which correlates with a poor prognosis. Dr. Ong’s laboratory is currently studying how mutations of that gene confer protection of prostate cancer cells from cell death and resistance to chemotherapy as well as how loss of PTEN influences progression of prostate cancer cells to androgen independence. Implications from this research may lead to new therapeutic strategies designed to prevent or delay progression to androgen independence. Based on observations to date, Dr. Ong is testing the potential utility of several classes of small molecule drugs that act to down-modulate the PI3K survival pathway in the treatment of prostate cancer. These novel compounds have tremendous promise as lead compounds for development of therapeutics that target a primary defect associated with prostate cancer and other malignancies. Dr. Ong's laboratory is also involved in the development of unique prostate tumour model systems which are used to characterize the function of a number of genes in normal and malignant prostate biology.
In collaboration with Drs. Alice Mui, Gerald Krystal and Raymond Andersen, Dr. Ong has also been involved in the discovery and development of a novel class of small molecule agonists of the SH2-containing inositol phosphatase, SHIP. From a high throughput SHIP enzyme screen of a natural product library consisting of organic extracts derived from marine invertebrates, Dr. Ong and his colleagues identified the meroterpinoid Pelorol from the Papua New Guinea sponge, Dactylospongia elegans, as a novel small molecule agonist of SHIP. Subsequently, synthetic structural analogs of the natural product possessing more potent biological activity were identified, namely AQX-016A and AQX-MN100. They have now devised an efficient, high yielding chemical synthetic protocol for production of this new family of compounds. Furthermore, they have performed extensive studies in wild-type and SHIP-deficient cells and in animal models of inflammation and cancer to demonstrate oral bioavailability, specificity, and efficacy of these compounds as a robust activator of SHIP and as a potent anti-inflammatory and anti-leukemia/lymphoma agent.