高大明研究员

文章出处: 作者: 发布时间: 2015-02-13 访问次数: 618

高大明,Ph.D

    研究员、博士生导师。

办公地点:中科院上海生命科学院生化细胞所,细胞楼709。

电话:021-54921281

Email: dgao@sibcb.ac.cn

教育背景

1997-2001山东大学生命科学学院生物科学专业理学学士

2001-2006中科院上海生命科学研究院生物化学与细胞生物学研究所生物化学与分子生物学专业博士

 

工作经历

2006-2010美国哈佛大学医学院(HMS/贝丝女执事医学中心(BIDMC)博士后

2010-2012美国哈佛大学医学院(HMS/贝丝女执事医学中心(BIDMC)讲师(Instructor

2012-至今中科院上海生命科学研究院生物化学与细胞生物学研究所研究员,研究组长

 

学术奖项与活动

2014 国家自然基金委优秀青年基金

2012 NIH/NCI K99 Pathway to Indenpendence Award (Awarded with perfect score, withdrawed before started as return to China)

2010 Lady Tata Memorial Trust Internatioanl Award for Leukemia Research

 

研究方向

1).肿瘤细胞信号转导机制:研究磷酸化、泛素化等蛋白翻译后修饰,及相关信号通路(如PI3K-mTOR激酶通路)对肿瘤细胞增殖迁移的调控分子机制。

2).细胞代谢调控机制:研究细胞内代谢通路(如糖酵解过程)对细胞增殖、生长和转化等生理过程的功能及相关分子调控机制。

 

主持的课题

1)国家自然科学基金委优秀青年基金, 肿瘤细胞增殖相关的蛋白泛素化降解(1/1/2015-12/31/2017)课题负责人

2) 国家重大科学研究计划资助(973项目), 小分子药物调控细胞命运及机理研究(1/1/2015-12/31/2019)课题负责人

3)国家自然科学基金委面上项目, 代谢酶PGK1 在肝癌细胞增殖中的功能与调控机制研究(1/1/2014-12/31/2017)课题负责人

 

代表性论文及论著

Original research articles

1.Lau AW, Liu P, Inuzuka H, Gao D. SIRT1 phosphorylation by AMP-activated protein kinase regulates p53 acetylation. Am J Cancer Res. 4(3):245-55, 2014

2.Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, Tsou P, Gan W, Papa A, Kim BM, Wan L, Singh A, Zhai B, Yuan M, Wang Z, Gygi SP, Lee TH, Lu KP, Toker A, Pandolfi PP, Asara JM, Kirschner MW, Sicinski P, Cantley L, Wei W.Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature. 508(7497):541-5, 2014

3.Liu P, Gan W, Inuzuka H, Lazorchak AS, Gao D, Arojo O, Liu D, Wan L, Zhai B, Yu Y, Yuan M, Kim BM, Shaik S, Menon S, Gygi SP, Lee TH, Asara JM, Manning BD, Blenis J, Su B, Wei W.Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis. Nat Cell Biol. 15(11):1340-50, 2013

4.Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D, Liu P, Lau AW, Wu T, Kirschner MW, Inuzuka H, Wei W.SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep. 4(4):803-16, 2013

5.Lau AW, Inuzuka H, Fukushima H, Wan L, Liu P, Gao D, Sun Y, Wei W.Regulation of APC(Cdh1) E3 ligase activity by the Fbw7/cyclin E signaling axis contributes to the tumor suppressor function of Fbw7. Cell Res. 23(7):947-61, 2013

6.Inuzuka H*, Gao D*, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, Wei W. Acetylation-dependent regulation of Skp2 function. Cell. 150(1):179-93, 2012 (* Co-first author),

7.Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, Harris L, Wan L, Fukushima H, Husain A, Nose V, Fadda G, Sadow PM, Goessling W, North T, Lawler J, Wei W. SCF(β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med. 2;209(7):1289-307, 2012

8.Fukushima H, Matsumoto A, Inuzuka H, Zhai B, Lau AW, Wan L, Gao D, Shaik S, Yuan M, Gygi SP, Jimi E, Asara JM, Nakayama K, Nakayama KI, Wei W. SCF(Fbw7) Modulates the NFκB Signaling Pathway by Targeting NFκB2 for Ubiquitination and Destruction. Cell Rep. 1(5):434-443, 2012

9.Wan L, Zou W, Gao D, Inuzuka H, Fukushima H, Berg AH, Drapp R, Shaik S, Hu Dorothy, Lester C, Eguren M, Malumbres M, Glimcher LH and Wei W. Cdh1 Regulates Osteoblast Function Through an APC/C-Independent Modulation of Smurf1. Mol Cell, 9;44(5):721-33, 2011

10. Gao D*, Inuzuka I*, Tan M*, Fukushima H, Locasale JW, Liu P, Wan L, Zhai B, Chin YR, Shaik S, Lyssiotis CA, Gygi SP, Toker A, Cantley LC, Asara JM, Harper JW and Wei W. mTOR drives its own activation via SCFβ-TRCP-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell, 44(2):290-303, 2011. (* Co-first author)

11.Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser R, Zhai B, Wan L, Gurierrez A, Lau A, Xiao Y, Christie A, Aster J, Settleman J, Gygi S, Kung AL, Look T, Nakayama KI, DePinho RA and Wei W. SCFFbw7 regulates cellular apoptosis by targeting the Mcl-1 oncoprotein for ubiquitination and destruction. Nature, 471:104-109, 2011

12.Gao D, Wan L, Inuzuka H, Berg AH, Tseng A, Zhai B, Shaik S, Bennet E, Tron AE, Gasser JA, Lau A, Gygi S, Harper JW, DeCaprio JA, Toker A and Wei W. Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction. Mol Cell, 39: 797-808, 2010

13.Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav L, Asara J, Xiao Z, Kaelin WG, Jr Harper JW and Wei W. Phosphorylation by Caesin Kinase I promotes the turnover of the Mdm2 oncoprotein via the SCFb-TRCP ubiquitin ligase. Cancer Cell, 18: 147-159, 2010

14.Singh A, Ye M, Bucur O, Zhu S, Tanya Santos M, Rabinovitz I, Wei W, Gao D, Hahn WC and Khosravi-Far R. Protein Phosphatase 2A Reactivates FOXO3a through a Dynamic Interplay with 14-3-3 and AKT. Mol Biol Cell, 21: 1140-1152, 2010

15.Gao D, Inuzuka H, Korenjak M, Tseng A, Wu T, Wan L, Kirschner M, Dyson N and Wei W. Cdh1 regulates cell cycle through modulating the Claspin/Chk1 and the Rb/E2F1 pathways. Mol Biol Cell, 20: 3305-3316, 2009

16.Gao D, Inuzuka H, Tseng A, Chin R, Toker A and Wei W. Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APC/Cdh1-medaited Skp2 destruction. Nat Cell Biol, 11: 397-408, 2009

17.Zhai J, Gao D, Liu W, Hong R, Qin Y, Ouyang H, Kong Y, Wang Y, Xie YH and Liu J. Characterization of a novel isoform of murine interferon regulatory factor 3. Biochem Biophys Res Commun, 377: 384-388, 2008

18.Gao D, Wang LF, Liu J, Kong YY, Wang Y and Xie YH. Expression of mouse liver receptor homologue 1 in embryonic stem cells is directed by a novel promoter. FEBS Lett, 580: 1702-1708, 2006

19.Chen X, Tong X, Xie YH, Wang Y, Ma J, Gao D, Wu H and Chen H. Over-expression and purification of isotopically labeled recombinant ligand-binding domain of orphan nuclear receptor human B1-binding factor/human liver receptor homologue 1 for NMR studies. Protein Expr Purif, 45: 99-106, 2006

20.Qin J, Gao D, Jiang QF, Zhou Q, Kong YY, Wang Y and Xie YH. Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-alpha-hydroxylase gene. Mol Endocrinol, 18: 2424-2439, 2004

Books and Chapters.

1.Wang Z, Fukushima H, Gao D, Inuzuka H, Wan L, Lau A.W, Liu P and Wei W. The two faces of FBW7 in cancer drug resistance. Bioessays, 33(11):851-9, 2011

2.Wang Z, Gao D, Fuhushima H, Inuzuka H, Liu P, Wan L, Sarkar FH and Wei W. Skp2: a novel potential therapeutic target for prostate cancer. BBA-Reviews on Cancer, 1825(1):11-17, 2011

3.Gao D, Wan L and Wei W. Phosphorylation of Rictor at Thr1135 impairs the Rictor/Cullin-1 complex to ubiquitinate SGK1. Protein Cell, 1: 881-885, 2010

4.Gao D, Inuzuka H, Tseng A and Wei W. Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1. Cell Div, 4: 11, 2009

5.Tseng A, Inuzuka H, Gao D, Singh A and Wei W. Experimental approaches to investigate the proteasomal degradation pathways involved in regulation of apoptosis. Methods Enzymol, 446: 205-223, 2008