徐華強

徐華強

徐華強,男,美國國籍,畢業於清華大學,在1985與1988年分別獲得學士與碩士學位,隨後於1994年獲得美國德州西南醫學中心博士學位,而後兩年在美國麻省理工學院從事博士後研究。1996年到2002年,先後在葛蘭素威康研究所和美國葛蘭素史克任研究員。2002年任美國Van Andel研究所結構科學實驗室主任,2007年提升為傑出教授和藥物研發中心主任。2010年7月以國家“千人計畫”特聘教授身份回到中國科學院上海藥物研究所並創建藥物靶結構與功能中心。 現任中國科學院受體結構與功能重點實驗室主任,中國科學院上海藥物研究所藥物靶標結構與功能中心主任、教授,中國科學院上海藥物研究所VARI/SIMM研究中心主任、傑出PI。

基本信息

簡介

1980-1985 清華大學核子物理工程專業,學士學位

1985-1988 清華大學生物物理專業,碩士學位

1989-1990 美國杜克大學植物遺傳系

1991-1994 美國德州大學西南醫學中心,生物化學與分子生物學專業,博士

1994-1996 美國麻省理工學院(MIT)生物系, 哈佛休斯醫學研究所,研究助理

1996-1999 美國格蘭素威康研究所結構化學系,一級研究院

1999-2001 美國格蘭素威康研究所結構化學系,二級研究員

2001-2002 美國GSK研究所結構科學部,高級研究人員

2002-2007.3 美國Van Andel研究所結構科學部實驗室負責人,資深PI/教授

2007.3-2009.12 美國Van Andel研究所結構科學部實驗室負責人,傑出PI/教授

2010.1-至今 美國Van Andel研究所結構科學與藥物發現中心主任,實驗室負責人,傑出PI/教授

2010.7-至今 擔任中國科學院上海藥物研究所研究員

研究方向

主要研究領域集中在核激素受體、肝臟生長因子(HGF)受體、G蛋白偶聯受體(GPCR)、離子通道和植物激素受體等結構與功能領域的研究,開展基於晶體結構的腫瘤與糖尿病的藥物研發。

職稱

研究員

主要研究成果

專利:1. Activators of PPAR delta. US Patent Number 6,710,063. Issued 03/23/2004.

2. Activator of PPAR delta. US Patent Number 6,723,740. Issued 04/20/2004.

3. Activator of PPAR delta. US Patent Application Serial Number 10/383,011. Filed 03/06/2003.

4. Crystallized PPARα Ligand Binding Domain Polypeptide and Screening Methods Employing Same. US Patent Application Serial Number 10/467,048. Filed 08/01/2003.

5. Crystallized Glucocorticoid Receptor Ligand Binding Domain Polypeptide and Screening Methods Employing Same. US Patent Application Serial Number 10/484,061. Filed 01/16/2004.

6. Ligands for Orphan Nuclear Hormone Receptor Steroidogenic Factor-1 (SF-1). US Patent Application Serial Number 11/348,207. Filed 02/06/2006.

7. Ligands for Mineralocorticoid Receptor (MR) and Methods for Screening for or Designing MR Ligands. PCT Patent Application Serial Number PCT/US2006/044620. Filed 11/15/2006.

文章:2009年發表ABA受體研究新成果文章“脫落酸受體晶體結構與分子機制” 發表在《自然》封面文章,被《科學》雜誌評為2009年十大突破之一。

已在《 Nature》、《 Science》、《 Cell》、《 Proc. Natl. Acad. Sci. USA》等雜誌發表論文110餘篇,並獲得專利十餘項。

承擔研究項目

1.973, 離子通道和膜轉運蛋白的結構與功能研究,2013.1-2017.8

2.重大專項, 基於GPCR結構與功能的藥物發現關鍵技術發展與平台建設, 2012.1-2015.12
3.基金委項目, 與神經系統疾病相關的離子通道的結構與功能研究, 2012.1-2015.12
4.基金委項目, 獨腳金內酯的信號傳導機制研究, 2013.1-2015.12

所獲榮譽

1993年獲美國德州大學西南醫學中心the Twenty-Fifth Sigma Xi研究生研究獎

1999年獲格蘭素威康傑出研究獎

2001年9月獲GSK傑出研究獎

2016年3月獲國際蛋白質學會Hans Neurath獎

2016年12月獲藥明康德生命化學研究獎傑出成就獎

代表學術論文

2009-2011年發表論文

2009-2011年發表論文

1.He Y, Xu Y, Zhang C, Gao X, Dykema, KJ, Martin KR, Ke J, Hudson EA, Khoo SK, Resau JH, Alberts AS, MacKeigan JP, Furge KA, and Xu HE (2011). Identification of a lysosomal pathway that potently modulates glucocorticoid signaling and inflammation response. Science Signaling (2011) (in press).

2.Serkan K, Beddow SA, Samuel VT, Miller P, Previs, SF, Suino-Powell K, Schulman G, Xu HE, Kliewer SA, and Mangelsdorf D (2011) FGF19 is a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science (in press)

3.Huh JR, Leung MWL, Huang P, Ryan DA, Krout MR, Malapaka R, Chow J, Manel N, Ciofani M, Kim SV, Cuesta A, Santori FR, Lafaille JJ, Xu HE, Gin DY, Rastinejad F, and Littman DR. (2011). Digoxin and its derivatives suppress Th17 cell differentiation by antagonizing RORγt activity.Nature (in press).

4.Zhou XE, Suino-Powell KM, Xu Y, Chan CW, Kruse SW, Reynolds R, Engel JD, Xu HE. (2010) The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor. J Biol Chem. 2010 Nov 9. [Epub ahead of print] (featured as Paper of the week)

5.Pal K, Swaminathan K, Xu HE, Pioszak AA.(2010). 2.Structural basis for hormone recognition by the human CRFR2alpha G protein-coupled receptor. J Biol Chem. 2010 Oct 21. [Epub ahead of print]

6.Melcher K, Zhou XE, and Xu HE (2010) Thirsty plants and beyond: structural mechanisms of abscisic acid perception and signaling. Current Opinion in Structural Biology (In press).

7.Tolbert WD, Daugherty-Holtrop J, Gherardi E, Vande Woude G, and Xu HE (2010) Structural basis for agonism and antagonism of hepatocyte growth factor. PNAS, 107:13264-9.

8.Melcher K, Xu Y, Ng LM, Zhou XE, Soon FF, Suino-Powell KM, Chinnusamy V, Kovach A, , Cutler SR, Li J, , Yong ELZhu JK, Xu HE (2010) Identification and Mechanism of ABA Receptor Antagonism. Nature Structural& Molecular Biology 17(9):1102-8.

9.Powell E, Huang SX, Xu Y, Rajski SR, Wang Y, Peters N, Guo S, Xu HE, Hoffmann FM, Shen B, Xu W. (2010) Identification and characterization of a novel estrogenic ligand actinopolymorphol A. Biochem Pharmacol. 80(8):1221-9. PMID: 20599778

10.Pal K, Kumar S, Sharma S, Garg SK, Alam MS, Xu HE, Agrawal P, Swaminathan K. (2010). Crystal Structure of Full-length Mycobacterium tuberculosis H37Rv Glycogen Branching Enzyme: INSIGHTS OF N-TERMINAL {BETA}-SANDWICH IN SUBSTRATE SPECIFICITY AND ENZYMATIC ACTIVITY. JBC 285(27):20897-903. EPUB 2010 MAY 5.

11.Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE. (2010) Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. JBC 285(16):12435-44. Epub 2010 Feb 19. PMID: 20172855

12.Zhou XE, Suino-Powell KM, Li J, He Y, Mackeigan JP, Melcher K, Yong EL, and Xu HE (2010) Identification of SRC3/AIB1 as A Preferred Coactivator for Hormone-Activated Androgen Receptor. JBC, January 19 Epub. (Featured as the cover article and the paper of the week by JBC). Mar 19;285(12):9161-71. PMID: 20086010

13.Schopfer FJ, Cole MP, Groeger A, Chen CS, Woodcock SR, Khoo N, Golin-Bisello F, Motanya UN, Rudolph TK, Rudolph V, Bonacci G, Baker PRS, Batthyany CI, Xu HE, Y. Chen YE, Hallis TM, and Freeman BA (2010) Covalent Peroxisome Proliferator-Activated Receptor γ Binding by Nitro-Fatty Acids: Endogenous Ligands Act as Selective Modulators. JBC, 2010 Apr 16;285(16):12321-33.

14.Epub 2010 Jan 22.Zhou XE, Suino-Powell K, Ludidi PL, McDonnell DP, Xu HE (2010) Expression, purification and primary crystallographic study of human androgen receptor in complex with DNA and coactivator motifs. Protein Expr Purif. 71(1):21-7.

15.Melcher K, Ng LM, Zhou XE, Soon FF, Xu Y, Suino-Powell KM, Park SY, Weiner JJ, Fujii H, Chinnusamy V, Kovach A, Li J, Wang Y, Li J, Peterson FC, Jensen DR, Yong EL, Volkman BF, Cutler SR, Zhu JK, Xu HE (2009) A gate-latch-lock mechanism for hormone signaling by abscisic acid receptors. Nature 2009 Dec 3;462(7273):602-8 (Cover Article, featured as one of top 10 breakthroughs of 2009 by Science). PMID: 19898420

16.Pioszak AA, and Xu HE. (2009) Molecular recognition of parathyroid hormone-related peptide (PTHrP) by the extracellular domain of its G protein-coupled receptor PTH1R. JBC, 2009 Aug 12. [Epub ahead of print] PMID: 19674967

17.Knudsen, BS., Zhao P, Resau J, Cottingham S, Gherardi E, Xu HE, Berghuis B, Daugherty J, Grabinski T, Toro J, Giambernardi T, Skinner RS, Gross M, Hudson E, Kort E, Lengyel E, Ventura A, West RA, Xie Q, Hay R, Vande Woude G, and Cao B. 2009. A novel multipurpose monoclonal antibody for evaluating human c-Met expression in preclinical and clinical settings. Applied Immunohistochemistry and Molecular Morphology 17(1): 56–67.

18.Wang Z, Zhou XE, et al, Xu HE, Mangelsdorf DJ. (2009) Control of Nematode Parasitism by Conserved Nuclear Receptor Signaling. PNAS 106, 9138-43.

19.Miao J, Kanamaluru D, Min G, Yau PM, Ellis E, Storm S, Suino-Powell K, Xu HE, Kemper JK (2009). Stability of Small Heterodimer Partner (SHP) is increased by bile acids and fibroblast growth factor 19. Genes and Development, 23:986-96.

20.Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RV, Xu HE, Turk J, and Semenkovich CF (2009) Identification of the Physiologically Relevant Endogenous Ligand for PPARα in Liver. Cell, 138(3):476-88. PMID: 19646743

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