本实验室主要兴趣在于：
1 细胞钙信号转导的微观过程和分子机理；
2 心脏疾病的分子病理机制和生物医学工程；
3 感觉传入诱导的大脑神经网络发育。
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。
分子间钙信号转导是心肌细胞兴奋收缩耦联的核心环节，其异常与心力衰竭、心律失常等重要疾病密切相关。我们最近在心衰分子病理机制方面取得突破，发现钙信号分子过程的病理改变远早于细胞和心肌组织的功能变化，其中关键分子事件是联系细胞膜与肌质网的蛋白junctophilin表达下降。我们正进一步寻找相关的分子调控机制，并在此基础上探索心衰早期诊断新技术和逆转心衰的生物医学工程方案。
脑和心脏一样是人体最重要的器官，均通过离子通道产生和传递兴奋。本实验室在研究生自由探索兴趣的驱使下，利用我们强有力的电生理优势和数据处理能力，以“同步发放链”理论框架为基础，通过分析不同感觉输入条件下神经细胞电活动的时序规律，研究后天经验如何影响大脑皮层神经网络的发育性构建，已取得重要阶段性发现。
Research Description:
We have three major lines of research: the microscopic aspects and underlying molecular mechanisms of intracellular Ca2+ signaling, the molecular basis and biomedical engineering of heart diseases, and the sensory input-directed development of cortical neural network.
Ca2+ is the most ancient and versatile intracellular messenger. Based on confocal microscopy and patch-clamp electrophysiology, we have developed state-of-the-art technologies for optical single-channel recording and intermolecular Ca2+ signaling. By combine these powerful tools with molecular biology, functional protomics and electron microscopy, we are probing the microscopic basis of the initiation, amplification, termination and regulation of intracellular Ca2+ signals.
Ca2+ signaling plays a central role in the excitation-contraction coupling of the heart. Miss-handling of intracellular Ca2+ results in fatal heart diseases, including heart failure and arrhythmia. As a breakthrough, we recently found that intermolecular failure of Ca2+ signaling well precedes cellular and global modification of heart function. A key related molecular event is the decreased expression of junctophilin, a protein anchoring sarcoplasmic reticulum to the cell membrane system. We are now going on to dissect the molecular mechanisms underlying the modifications, and develop new technologies for early diagnosis and treatment of heart failure.
Brain and heart are both the most important organs of vertebrates, fulfilling their functions by generating and transmitting excitation. Driven by their interests in the “synfire chains” neural circuitry theory, a group of students in our lab are probing how the construction of cortical neural network is guided by sensory experience. Utilizing the electrophysiology facility and data processing capacity in our lab, they are making encouraging progress in relating the neuronal firing patterns to the nature of sensory inputs.
代表性论文
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 , doi: 10.1161/?CIRCRESAHA.114.302938
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. 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: 837-841
4. 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: 430-438
5. Zhou P, Zhao YT, Guo YB, Xu SM, Bai SH, Lakatta EG, Cheng H, Hao XM, Wang SQ* , Beta-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: 18028-18033
6. 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
7. 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.
8. Wang SQ, Stern MD, Ríos E, Cheng H , The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array , Proc. Natl. Acad. Sci. U. S. A. , 2004 , 101: 3979-3984
9. Wang SQ, Wei CL, Zhao GL, Brochet DXP, et al , Imaging microdomain Ca2+ in muscle cells , Circ. Res. , 2004 , 94: 1011-1022
10. Wang SQ ,Song LS, Lakatta EG, Cheng H , Ca2+ signaling between single L-type Ca2+ channels and ryanodine receptors in heart cells , Nature , 2001 , 410: 592-596. |
