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团队成员

蒋洪

学历:博士研究生
职称:研究员
邮箱:HongJiang@sioc.ac.cn
电话:68582396
地址:上海市浦东新区海科路100号

简介

1994-1998 中国科学技术大学 学士
University of Science and Technology of China B.S.
1998-2003 中国科学技术大学 博士
University of Science and Technology of China Ph.D
2003-2006 美国华盛顿大学 博士后
Washington University in St. Louis Postdoc
2006-2009 美国康奈尔大学 访问科学家
Cornell University Visiting Scientist
2009-2015 美国康奈尔大学 副研究员
Cornell University Research Associate
2015.9-至今 中国科学院生物与化学交叉研究中心 研究员、课题组长

研究方向

二核苷酸(环二核苷酸CDN和烟酰胺腺嘌呤二核苷酸NAD)是细胞内重要的代谢小分子。细菌衍生的CDN能激活哺乳动物宿主细胞的先天性免疫反应,被认为是治疗耐药菌感染的极具潜力的免疫治疗剂。哺乳动物中内源性CDN,同样在天然免疫信号通路中发挥着重要的第二信使作用,这一全新发现为癌症免疫治疗奠定了理论基础。另一方面,NAD作为生物体中一个至关重要的有机分子,不仅在能量传递中起着关键性作用,还广泛参与多条信号传导途径,进而调控包括基因转录、DNA修复、细胞周期进程、细胞凋亡和代谢在内的多个重要生命过程。与NAD紧密相关的NAD代谢酶被认为是肿瘤和神经退化性疾病治疗中极具开发前景的靶点蛋白。

本实验室将结合生物化学、细胞与分子生物学和有机合成,对二核苷酸(CDN和NAD)及其代谢酶的调控机制和生物功能开展全方位的化学生物学研究工作,从一个全新的视角进一步认识蛋白翻译后修饰、细胞代谢调控、免疫反应和神经组织退化的分子机制,为治疗感染性疾病、自身免疫性疾病和神经退化性疾病提供新的思路,并积极地推动新型治疗药物的开发。

代表论文

1. Revealing CD38 cellular localization using a cell permeable, mechanism-based fluorescent small-molecule probe.
Shrimp, J.H.; Hu, J.; Dong, M.; Wang, B.S.; MacDonald, R.;Jiang, H.;Hao, Q.; Yen, A.; Lin, H.
J. Am. Chem. Soc., 2014, 136, 5656-5663.


2. SIRT6 Regulates TNF-alpha Secretion through Hydrolysis of Long-Chain Fatty Acyl Lysine.
Jiang, H. ¶; Khan, S. ¶; Wang, Y. ¶; Charron, G.; He, B.; Sebastian, C.; Du, J.; Kim, R.; Ge, E.;Mostoslavsky, R.; Hang, H. C.; Hao, Q.; Lin, H.
Nature, 2013, 496, 110-113. (¶ Authors contributed equally.)


3. Identification of ADP-ribosylation Sites of CD38 Mutants by Precursor Ion Scanning Mass Spectrometry.
Jiang, H.; Sherwood, R.; Zhang, S.; Zhu, X.; Liu, Q.; Graeff, R.; Kriksunov, I. A.; Lee, H. C.; Hao, Q.; Lin, H.
Anal.Biochem., 2013, 433, 218-226.


4. Chemogenomic Approach Identified Yeast YLR143W as DiphthamideSynthetase.
Su, X.; Lin, Z.; Chen, W.; Jiang, H.; Zhang, S.; Lin, H.
Proc. Natl. Acad. Sci. U S A., 2012, 109, 19983-19987.


5. Labeling Substrate Proteins of Poly(ADP-ribose) Polymerases with Clickable NAD Analogue
Jiang, H.; Lin, H.
Current Protocols in Chemical Biology, 2012, 4, 19-34.


6. YBR246W is Required for the Third Step of Diphthamide Biosynthesis.
Su, X.; Chen, W.; Lee, W.; Jiang, H.; Zhang, S.; Lin, H.
J. Am. Chem. Soc., 2012, 134, 773-776.


7. Sirt5 is an NAD-dependent Protein Lysine Demalonylase and Desuccinylase.
Du, J.; Zhou, Y.; Su, X.; Yu, J. J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Kim, J.-H.; Choi, B. H.; He, B.; Zhang, S.; Cerione, R. A.; Auwerx, J.; Hao, Q.; Lin, H.
Science, 2011, 334, 806-809.


8. ATRA-induced HL-60 Myeloid Leukemia Cell Differentiation Depends on the CD38 Cytosolic Tail Needed for Membrane Localization, but CD38 Enzymatic Activity is Unnecessary.
Congleton, J.; Jiang, H.; Malavasi, F.; Lin, H.; Yen, A.
Exp. Cell Res., 2011, 317, 910-919.


9. Clickable NAD Analogues for Labeling Substrate Proteins of Poly(ADP-ribose) Polymerases.
Jiang, H.; Kim, J. H.; Frizzell, K.; Kraus, W. L.; Lin, H.
J. Am. Chem. Soc., 2010, 132, 9363-9372.


10. Structural Basis for Enzymatic Evolution from a Dedicated ADP-ribosyl Cyclase to a Multi-functional NAD Hydrolase.
Liu, Q.; Graeff, R.; Kriksunov, I. A.; Jiang, H.; Zhang, B.; Oppenheimer, N.; Lin, H.; Potter, B. V. L.; Lee, H. C.; Hao, Q.
J. Biol. Chem., 2009, 284, 27637-27645.


11. The Partial Substrate Dethiaacetyl -Coenzyme A Mimics All Critical Carbon Acid Reactions in the Condensation Half-Reaction Catalyzed by Thermoplasmaacidophilum Citrate Synthase.
Kurz, L. C.; Constantine, C. Z.; Jiang, H.; Kappock, T. J.
Biochemistry, 2009, 48, 7878-7891.


12. Mechanism-Based Small Molecule Probes for Labeling CD38 on Live Cells.
Jiang, H.; Congleton, J.; Liu, Q.; Merchant, P.; Malavasi, F.; Lee, H. C. ; Hao, Q.; Yen, A.; Lin, H.
J. Am. Chem. Soc., 2009, 131, 1658-1659.


13. Investigating the ADP-ribosyltransferase Activity of Sirtuins with NAD Analogs and 32P-NAD.
Du, J.; Jiang, H.; Lin, H.
Biochemistry, 2009, 48, 2878–2890.


14. A Study on the Reactions of NADH Models with Electron-Deficient Alkenes. A Probe for the Extreme of Concerted Electron-Hydrogen Atom Transfer Mechanism.
Fang, X.-Q.; Xu, H.-J.; Jiang, H.; Liu, Y.-C.; Fu, Y.; Wu, Y.-D.
Tetrahedron Lett., 2009, 50, 312-315.


15. Covalent and Non-CovalentIntermediates of an NAD Utilizing Enzyme - Human CD38.
Liu, Q.; Kriksunov, I.A.; Jiang, H.; Graeff, R.; Lin, H.; Lee, H.C.; Hao, Q.
Chem. Biol., 2008, 15,1068-1078.


16. Multiple Active Site Histidine Protonation States in Acetobacteraceti N5-Carboxyaminoimidazole Ribonucleotide Mutase Detected by REDOR NMR.
Schaefer, J.; Jiang, H.; Ransome, A. E.; Kappock, T. J.
Biochemistry, 2007, 46, 9507-9512.


17. Structure of a NADH-Insensitive Hexameric Citrate Synthase that Resists Acid Inactivation.
Francois, J. A.; Starks, C. M., Sivanuntakorn, S.; Jiang, H.; Ransome, A. E.; Nam, J.-W.; Constantine, C. Z.; Kappock, T. J.
Biochemistry, 2006, 45, 13487-13499.


18. Photo-induced Coupling Reaction of 1,1-Diphenyl-2,2-dicyano-ethylene with 10-Methyl-9,10-dihydroacridine.
Jiang, H.; Liu, Y.-C.; Wang, G.-W.; Wu, Y.-D.; Wang, Q.-M.; Mak, T. C. W.
Chinese Chem. Lett., 2004, 15, 159-162.


19. Novel Photo-induced Coupling Reactions of 9-Fluorenylidenemalononitrile or 1,1-Diphenyl-2,2-dicyanoethylene with 10-Methyl-9,10-dihydroacridine. A Study on the Photophysics of the Reaction.
Jiang, H.; Liu, Y.-C.; Wang, G.-W.; Wu, L.-Z.; Tong, Z.-H.
Chinese J. Chem., 2003, 21, 1400-1402.


20. Novel Photo-induced Coupling Reaction of 9-Fluorenylidenemalononitrile with 10-Methyl-9,10-dihydroacridine.
Jiang, H.; Liu, Y.-C.; Li J.; Wang, G.-W.; Wu, Y.-D.; Wang, Q.-M.; Mak, T. C. W.
Chem. Commun., 2002, 882-883.

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