Yanping Hu - Research Home Page [Advanced Therapeutics : BC Cancer Research Centre]

Advanced Therapeutics

Dr. Yanping Hu

yhu@bccancer.bc.ca

Research Associate

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Department:	Advanced Therapeutics (@ the BCCRC since 1999)
Research Role:	Graduate Student/Postdoctoral Fellow Alumnus
Education:	PhD (Pharmacology), University of Bordeaux II, France MSc (Pharmacology), BSc, (Pharmacy), Henan Medical University, China
Birthplace:	Nanjing, China
Phone:	604-675-8000 ext.3133
Fax:	604-877-6011

Research Interests:

Nearly half of human cancers are resistant to a wide variety of structurally and functionally unrelated anticancer drugs. My research interest is to develop strategies to overcome multidrug resistance (MDR) and increase chemosensitivity of tumour cells typically considered responsive to anticancer drugs. The evidence suggests that many anticancer agents induce cytotoxic effects via apoptosis, which has raised a great interest in development of different approaches to chemosensitise tumor cells by altering regulation of apoptosis. The decision as to whether a cell undergoes apoptosis or continues to progress through the cells cycle is dependent on the interplay of a complex set of genes and proteins that interact to regulate a cell cycle progression. Particularly, Bcl-2 and XIAP are the most attractive targets in terms of its ability to directly inhibit caspases and to suppress apoptosis in many types of cancers. My recent studies suggest that antisense oligonucleotides (small segments of synthetic DNA) directed against bcl-2 or xiap mRNA have anti-tumour activities both in various tumour cell lines and tumour xenograft models. Also, I have shown that the combination of Bcl-2 and XIAP antisense with conventional chemotherapeutic agents like vinorelbin produced enhanced anti-tumour activity against human lung cancer xenografts. These preclinical studies have attracted medical oncologist interest to perform clinical trials. In addition to targeting specific proteins involved in inhibition of the apoptotic machinery, modulation of cell signalling pathways that control cellular proliferation may provide an alternative strategy for inducing cell death and increasing susceptibility to apoptosis. I have used a high throughput screening system to identify protein kinases and phosphatases associated with tumour cell proliferation in order to determine changes of these kinases in tumour cells under different stress conditions. Next, I tried to downregulate protein kinases such as MER/ERK, protein kinase C and AKT/PKB etc. using specific kinases inhibitors. Consequently, I have demonstrated an increased apoptosis and sensitisation of tumour cells to chemotherapy. Evaluation of these inhibitors in human xenograft tumour models is being performed to obtain in vivo efficacy. Also, an attention is given to new agents that exhibit novel mechanisms of action and/or toxicity profiles that are complementary or far superior to existing anticancer drugs. However, treatment with certain conventional anticancer drugs, small molecule compounds, and monoclonal antibodies targeting oncogenic molecules such as Her-2 and castration may increase hypoxia in solid tumors. My current work is focused on studying molecular basis of hypoxia regulation in vitro and in vivo in order to find new therapeutic targets and to come up with new initiatives in cancer treatment by exploiting the hypersensitivity of hypoxia tumor cells to inhibitors of glycolysis, which is a common metabolic pathway in hypoxic cells. The rational design of drugs that simultaneously attack biochemical targets described above in combination with conventional anticancer drugs is another area of my research interest. These studies resulted in finding effective synergistic drug combinations to treat tumor cells. However, it is a great challenge to produce drug synergistic effects and suppress the emergence of MDR in human tumor xenograft models.