药学院学术报告
报告题目: HIF pathway: its regulation and potential as therapeutic target
报告人: 吴寿荣 博士 (Graduate School of Medicine, The University of Tokyo )
报告时间:
报告地点: 独墅湖2期云轩楼1319室
报告摘要:
The regulation of angiogenesis by hypoxia is an important mechanism that link vascular oxygen supply to cellular metabolic. Hypoxia-inducible factor (HIF) pathway has been known to be a key role in hypoxia-induced angiogenesis, and recent studies showed that the understanding of HIF pathway has provided new insight into vessel-relative diseases. Here we investigated the key role of HIF regulation in ischemia disease and cancer therapy. (1) HIF pathway and ischemia disease: Ischemia, which affects hundreds of millions of people worldwide, occurs when blood vessels in tissues are blocked. The therapeutic strategy aims to improve neovascularization in ischemic tissues by delivery of angiogenic factor proteins or DNA vectors encoding them. Hypoxia-inducible factor-1 (HIF-1) is a master factor of hypoxia-induced angiogenesis in ischemic tissue. Recent study showed that inactivation of PHD2 contributes to HIF-1 stabilization. However, the detailed mechanisms that regulate angiogenesis factors and the potential biological function of PHD2 are completely unknown. Here we showed that PHD2-silencing could induce multiple angiogenic factors via both HIF-dependent and independent manners, and investigated its therapeutic angiogenesis potential. (2) HIF pathway and anti-angiogenesis therapy: Hypoxia is a common condition found in a wide range of solid tumors, and increases tumor angiogenesis, survival responses, as well as tumor invasion and metastasis by activation of relevant genes through HIF pathways. Furthermore, activation of HIF-1a is a common feature of cancer cells, and its levels and activities are tightly correlated with poor outcomes in the majority of malignancies. However, their mechanisms still had not been completely understood. Here we found that the ablation of transcription factor Yin Yang 1 (YY1) resulted in the reduction of HIF-1a and angiogenesis-related growth factors in hypoxia condition. We investigated YY1 as a key regulator of HIF-a in tumor progression, and suggested YY1 inhibition as a potential therapeutic strategy through the downregulation of HIF-1a.
吴寿荣简介：
Education:
B.Sc Shenyang Pharmaceutical University, 1999；M.Sc Shenyang Pharmaceutical University, 2002； Ph.D. Department of Chemistry and Biotechnology, Graduate
Professional Experience:
2008-2009 Fellowship Researcher,
2009-Present JSPS (Japan Society for the Promotion of Science) researcher, Graduate School of Medicine, The University of Tokyo
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