方敏 |
科研领域描述
There are two primary lines of investigation currently in progress in my laboratory: cancer metabolism and cell death.
1. Cancer is historically well characterized as an energetically adaptive metabolic disease. Metabolic re-programming events coincide with every stage of cancer development ranging from initiation to metastasis. Unfortunately, the biochemical studies of metabolic re-programming in cancer cells have been largely overshadowed by efforts to identify the mutations that contribute to cancer initiation and progression, including oncogenes such as Myc, Ras, PI3K, Akt and tumor suppressors such as PTEN and P53. Until recently, oncogenes and tumor suppressors are believed to be the cause of metabolic re-programming events in variety of cancers. However, mutations in metabolic flux regulatory enzymes such as fumerate hydrotase; succinate dehydrogenase and isocitrate dehydrogenase, can initiate cancer, highlighting the importance of metabolic regulation. Therefore, metabolic transitions in cancer cells are considered as an “Achilles’ heel” for potential chemotherapy. Based on this notion, my lab will devote our efforts to dissecting individual dys-regulated enzymatic reactions out of the complicated metabolic networks in cancer cells, establishing in vitro functional assays which faithfully mimic the in-vivo biologic relevance, and eventually purifying components responsible for metabolic re-programming during cancer initiation, progression, and metastasis. Our ultimate goal is to identify small molecular chemicals which could correct specific dys-regulated enzymatic activities both in-vitro and in-vivo, and reverse metabolic re-programming events in cancer cells.
2. Development of eukaryotic organisms requires fine-tuned spatial and temporal regulation of cell demise, including apoptotic, necrotic and autophagic cell death. Among them, abnormal regulation of apoptosis, a major form of cell elimination, is closely related to cancer and neurodegenerative diseases. Different forms of cell death are triggered by different sets of devastating enzymes such as proteases, nucleases as well as lipases. How the intra- or extracellular signals ignite and amplify specific enzymatic cascades and subsequently converge on different intracellular constituents such as cell membrane, cytosol, Mitochondria, ER, Lysosome, Peroxisome, Nucleus, and eventually execute cell elimination, has emerged as a key question of cell death research during the last decade. By combining classic biochemical approaches with cell biology, molecular biology and genetic methodology, my laboratory will focus on identifying factors which specifically contribute to abnormal regulation of cell death in various tumors as well as neurodegenerative diseases. Integrating in-vitro functional assays with high-throughput screening technology, we seek to develop novel strategies to further improve chemotherapy and ameliorate progression of neurodegenerative diseases.
代表性论文
1. Fang M., Shen Z., Huang S., Zhao L., Chen S., Mak T.W. and Wang X. , The endoplasmic reticulum UDPase ENTPD5 promotes protein N-glycosylation, the Warburg Effect and proliferation in the PTEN pathway. , Cell , 2010 , 143: 711-724. , [Abstract] , [Full Text]
2. Hao Z., Duncan G.S., Chang C.C., Elia A., Fang M., Wakeham, A., Okada H., Calzascia T., Jang Y., You-Ten A., Yeh W.C., Ohash P., Wang X., and Mak T.W. , Specific ablation of the apoptotic function of cytochrome c in mice leads to neurological abnormalities and impaired lymphocyte homeostasis. , Cell , 2005 , 121: 579-591. , [Abstract] , [Full Text]
3. Kim HE, Du F., Fang M. and Wang X. , Formation of apoptosome is initiated by cytochrome c-induced dATP hydrolysis and subsequent nucleotide exchange on Apaf-1. , Proc Natl Acad Sci USA , 2005 , 102: 17545-550. , [Abstract] , [Full Text]
4. Nijhawan D.*, Fang M.*, Traer E., Zhong Q., Gao W., Du F., and Wang X. , Elimination of Mcl-1 is required for the initiation of apoptosis following ultraviolet irradiation. , Genes and Development , 2003 , 27: 1475-1486. (* equal contribution). , [Abstract] , [Full Text]
5. Du C., Fang M., Li Y., Li L., and Wang, X. , Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation during apoptosis. , Cell , 2000 , 102: 33-42. , [Abstract] , [Full Text]
6. Lutter M., Fang M., Luo X., Nishijima M, Xie X., and Wang X. , Cardiolipin provides specificity for targeting of tBid to mitochondrial , Nature Cell Biology , 2000 , 2: 754-756. , [Abstract] , [Full Text] |
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