2017年3月30日 星期四
王世强
王世强
教授(Professor Shi-Qiang Wang)

北京大学生命科学学院教授,博士生导师,膜生物学国家重点实验室主任,中国生理学会副理事长。1998年获北京大学博士学位,2004年获国家杰出青年基金,2006年获聘教育部“长江学者”,2009年入选百千万人才工程国家级人选,2014年入选国家科技创新推进计划中青年科技创新领军人才。长期从事钙通道信号转导研究,在我国率先使用共聚焦成像技术研究钙信号动态,在国际上首先探测并命名单个钙通道Cav1.2产生的钙信号单位“钙小星” ;提出并证明肌质网钙释放通道RyR2热力学不可逆变构学说;定量分析心衰早期Cav1.2-RyR2信号耦联的病理变化;阐明β肾上腺素受体调控RyR2的关键机制,解决了该领域十几年的学术争论;阐明JP2和miR-24对细胞膜-肌质网钙信号耦联的决定性调控作用;参与发现并命名纳米钙火花。系列成果在Nature、PNAS等刊发表论文80多篇,被引2000多篇次。曾获中国生理学会张锡钧一等奖、美国心脏学会Katz基础科学研究奖、国际心脏研究会Richard Bing奖、北京市优秀教师、教育部高校青年教师奖、卫生部心血管中心有突出影响论文奖、国务院政府津贴、全国优秀科技工作者等学术奖励。 

主要研究领域:细胞钙信号转导的微观过程和分子机理 

 钙离子是细胞最古老、作用最广泛的胞内信使。本实验室在激光共聚焦显微成像技术和膜片钳电生理技术的基础上,建立了单通道光学探测和通道间钙信号转导的研究技术,在国际上居领先优势。将该技术与分子生物学、功能蛋白组学、电子显微镜技术相配合,可以从分子间相互作用的微观水平阐述细胞钙信号是如何产生、放大和精细调控的。分子间钙信号转导的异常与心力衰竭、心律失常等重要疾病密切相关。我们通过揭示细胞钙信号动态及其精细调控过程的异常,揭示有关心脏疾病的分子机理,为其早期诊断和治疗探索新思路。 

Research Interests : Microscopic process and molecular mechanism of calcium signal transduction in cells

The molecular basis of intracellular Ca2+ signaling. He combines state-of-the-art confocal imaging, single-channel patch clamping, single-molecule tracing with molecular cell biology techniques to dissect the molecular mechanisms underlying the generation, amplification and termination of intracellular Ca2+ dynamics, aiming to answer important questions about the function, development and dysfunction of the heart and brain. 

代表性论文(*通讯作者)

1.Shang W, Lu F, Sun T, Xu J, Li LL, Wang Y, Wang G, Chen L, Wang X, Cannell MB, Wang SQ*, Cheng H*. Imaging Ca2+ Nanosparks in Heart with a New Targeted Biosensor. Circulation Research, 2014, 114(3): 412-420.【述评: Zhao YT & Valdivia. Ca2+ nanosparks: shining light on the dyadic cleft. Circulation Research】
 
2.Li RC, Tao J, Guo YB, Wu HD, Liu RF, Bai Y, Lv ZZ, Luo GZ, Li LL, Wang M, Yang HQ, Gao W, Han QD, Zhang YY, Wang XJ, Xu M, Wang SQ*. In Vivo Suppression of MicroRNA-24 Prevents the Transition Toward Decompensated Hypertrophy in Aortic-Constricted Mice. Circulation Research. 2013, 112: 601-605.
 
3.Han J, Wang QW, Wang SQ*. Fluorescent tag is not a reliable marker for small RNA transfection in the presence of serum. J. Biosci. 2013, 38: 471-478.
 
4.Han J, Wu HD, Wang QW, Wang SQ*. Morphogenesis of T-tubules in heart cells: the role of junctophilin-2. Sci. China Life Sci. 2013, 56(7): 647-652.
 
5.Zhang HB, Li RC, Xu M, Xu SM, Lai YS, Wu HD, Xie XJ, Gao W, Ye H, Zhang YY, Meng X, Wang SQ*. Ultrastructural Uncoupling between T-tubules and Sarcoplasmic Reticulum in Human Heart Failure. Cardiovasc. Res. 2013, 98(2): 269-276.
 
6.Xu M, Wu HD, Li RC, Zhang HB, Wang M, Tao J, Feng XH, Guo YB, Li SF, Lai ST, Zhou P, Li LL, Yang HQ, Luo GZ, Bai Y, Xi JZ J., Gao W, Han QD, Zhang YY, Wang XJ*, Meng X, and Wang SQ*. MiR-24 regulates junctophilin-2 expression in cardiomyocytes. Circulation Research. 2012, 111(7): 837-841.【述评: Song LS, et al. MicroRNA: a toolkit fine-tuning the dyadic "fuzzy space"? Circulation Research 111:816-818】
 
7.Wu HD, Xu M, Li RC, Guo L, Lai YS, Xu SM, Li ll, Lü QL, Zhang HB, Zhang YY, Zhang CM and Wang SQ* , Ultrastructural Remodeling of Ca2+ Signaling Apparatus in Failing Heart Cells. Cardiovascular Research. 2012, 95(4): 430-438.【述评: Swift F, Christensen G. Calcium release units in heart failure: that's about the size of it. Cardiovascular Research 95: 397-398】
 
8.Xu XF, Xin Y, Wang JS, Zhao L, Du LP, Ge GL, Li N, Zhang Y, Wang SQ, Huang YM, Luo Y. Expression of GFP and Luc reporter genes driven by human myocardial myosin light chain gene promoter in human cardiomyocytes. Chin. J. Pathophysiol. 2012, 28: 1722-1728.
 
9.Zhang HB, Meng X, Han J, Li Y, Jia YX, Lai YS, Wang SQ. Ultra-structure compare of normal left ventricle with chronic heart failure. J. Cardiov. Pulmonary Diseases. 2011, 30: 136-139.
 
10.Wu HD, Wang SQ, Meng X, Zhang HB. Structural and functional coupling and pathological remodeling of cell membrane and sarcoplasmic reticulum in cardiomyocytes. Life Sci. (Shanghai). 2011, 23: 1-7.
 
11.Wang SQ*, Zhu MX, Carafoli E. Ca2+: a versatile master key for intracellular signaling cascades. Sci. China Life Sci. 2011, 54(8): 683-685.
 
12.Li XC, Wei L, Zhang GQ, Bai ZL, Hu YY, Zhou Z, Bai SH, Chai Z, Lakatta EG, Hao XM, Wang SQ*. Ca2+ cycling in heart cells from ground squirrels: adaptive strategies for intracellular Ca2+ homeostasis. PLoS One. 2011, 6(9): e24787.
 
13.Cheng H, Fang HQ, Chen M, Ding Y, Shang W, Zhang X, Xu JJ, Zhang WR, Li KT, Xiao Y, Gao F, Shang SJ, Li JC, Tian XL, Wang SQ, Zhou JS, Weisleder N, Ma JJ, Ouyang KF, Chen J, Wang XH, Zheng M, Wang W, Zhang XQ. Imaging superoxide flash and metabolism-coupled mitochondrial permeability transition in living animals. Cell Res. 2011, 21(9): 1295-1304.
 
14.Guo YB, Wen Y, Gao WX, Li JC, Zhou P, Bai ZL, Zhang B and Wang SQ*. The formation of Ca2+ gradients at the cleavage furrows during cytokinesis of Zebrafish embryos. Front. Biol. 2010, 5(4): 369-377.
 
15.Zhou P, Zhao YT, Guo YB, Xu SM, Bai SH, Lakatta EG, Cheng H, Hao XM, Wang SQ*. b-Adrenergic signaling accelerates and synchronizes cardiac ryanodine receptor response to a single L-type Ca2+ channel. Proc. Natl. Acad. Sci. U. S. A. 2009, 106(42): 18028-18033.
 
16.Tang AH, Wang SQ*. Transition of spiral calcium waves between multiple stable patterns can be triggered by a single calcium spark in a fire-diffuse-fire model.Chaos. 2009, 19(3): No. 037114.
 
17.Xu M, Zhou P, Xu SM, Liu Y, Feng XH, Bai SH, Bai Y, Hao XM, Han QD, Zhang YY*, Wang SQ*. Intermolecular Failure of L-type Ca2+ Channel and Ryanodine Receptor Signaling in Hypertrophy. PLoS Biol. 2007, 5: e21, 0203-0211. (Highlighted by: Harrison C. Heart disease: Unmasking molecular mechanisms. Nature Reviews Drug Discovery. 2007, 6: 271.)
 
18.Zhou C, Tai C, Ye HH, Ren X, Chen JG, Wang SQ*, Chai Z*. Interleukin-1bdownregulates the L-type Ca2+ channel activity by depressing the expression of channel protein in cortical neurons. J. Cell. Physiol. 2006, 206(3): 799-806.
 
19.Fu Y, Zhang GQ, Hao XM*, Wu CH, Chai Z, Wang SQ*. Temperature Dependence and Thermodynamic Properties of Ca2+ Sparks in Rat Cardiomyocyte. Biophys. J. 2005, 89(4): 2533-2541.
 
20.Wang SQ, Stern MD, Ríos E, Cheng H*. The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells. Proc. Natl. Acad. Sci. U. S. A. 2004, 101(11): 3979-3984.
 
21.Wang SQ, Wei CL, Zhao GL, Brochet DXP, et al. Imaging microdomain Ca2+ in muscle cells. Circ. Res. 2004, 94(8): 1011-1022.
 
22.Zhu WZ, Wang SQ, Khalid C, Yang DM, et al. Linkage of b1-adrenergic stimulation to apoptotic heart cell death through protein kinase A-independent activation of Ca2+/calmodulin kinase II. J. Clin. Invest. 2003, 111:617-625.
 
23.Wang SQ, Song LS, Xu L, Meissner G, et al. Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks. Biophys. J. 2002, 83(1): 242-251.
 
24.Wang SQ, Song LS, Lakatta EG, Cheng H. Ca2+signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells. Nature.2001, 410(6828): 592-596.