基本信息
教育经历
工作经历
研究概述
发表文章

张二荃 博士

北京生命科学研究所研究员

E. Erquan Zhang, Ph.D. Assistant Investigator, NIBS, Beijing，China

Phone：-8605

Fax：

E-mail：zhangerquan@nibs.ac.cn


教育经历
Education
2000 – 2004
美国加州大学圣地亚哥分校分子病理专业博士


Ph.D. in Molecular Pathology, University of California – San Diego,La Jolla, California, USA

1994 – 1997
复旦大学生物化学专业硕士


M.S. in Biochemistry,FudanUniversity,Shanghai,China

1990 – 1994
华东师范大学环境科学专业学士


B.S. in Environmental Science,EastChinaNormalUniversity,Shanghai,China


工作经历
Professional Experience
2011 –
北京生命科学研究所研究员

Assistant Investigator, National Institute of Biological Sciences, Beijing, China

2006 – 2010
美国诺华制药加州圣地亚哥研究院高级博士后研究员；兼美国加州大学圣地亚哥分校生物科学学院访问****

Institute Fellow, Genomics Institute of the Novartis Research Foundation, San Diego, California, USA; Visiting Scholar, Division of Biological Sciences, University of California – San Diego, La Jolla, California, USA

2004 – 2006
美国加州斯科瑞普斯研究所博士后

Postdoctoral Associate, The Scripps Research Institute, La Jolla, California, USA


研究概述
生物钟对人类行为与生理有广泛的调节作用。我们对生物钟研究领域各个方面都感兴趣，主要想回答三大问题：什么是生物钟？生物钟如何进行调控？研究生物钟有何重要意义？目前我们对以下几个子课题特别感兴趣：
1.
对于哺乳动物的生物钟而言，一个简单的模型就是转录因子形成的延迟负反馈系统：转录正因子CLOCK和BMAL1结合，激活转录负因子PERIOD（包括PER1, PER2, PER3；简称PER）和CRYPTOCHROME（CRY1, CRY2；简称CRY）。PER与CRY表达积累到一定程度会反过来抑制CLOCK-BMAL1的活性，从而导致PER-CRY表达降低，形成每循环约24小时的负反馈环路。早期的小鼠行为筛选以及最近的全基因siRNA筛选都显示有更多的生物钟基因存在。我们准备运用系统生物学结合小鼠遗传学方法研究新的生物钟基因及其调控转录的分子机理，更深入理解生物钟振荡器的相位，振幅，及周期。

2.
视交叉上核（SCN）是负责生物钟调控的主要器官，位于下丘脑前端。前期研究表明，SCN中存在一种特异性的分子机制暂时不明的耦合机理，促使其内的生物钟异常强劲。我们准备运用合成生物学方法改造成纤维细胞，外加某种假设的耦合机理，使其变成SCN神经细胞。如获得成功，我们就不仅解释了耦合的分子机理，也会提供足够的材料作生化分析，用以更深层次的解释何以SCN区别于其它组织而作为生物钟调控的中心。

3.
生物钟失调会导致代谢紊乱。为了充分发挥本研究员以前做高通量筛选（HTS）的特长已及应用NIBS拥有的最先进的HTS设备，我们会用此技术开创几个探索性课题，用以了解生物钟对酒精代谢和脂肪肝形成的影响。从这些细胞筛选方法得到的假说，我们会进一步运用小鼠遗传学等体内方法来加以验证。


Research Description
Circadian clock regulates human behavior and physiology. We are interested in understanding all aspects of circadian rhythms: What is the clock? How does the clock run? Why is the clock relevant? In particular, we focus on several projects in dissecting the clock mechanism and highlighting its biological/biomedical significance:
1.
In a simplified model, transcriptional activators CLOCK and BMAL1 stimulate PERIOD (PER1, PER2 and PER3) and CRYPTOCHROME (CRY1, CRY2) repressors that feed back on CLOCK-BMAL1 activity. Both mouse behavioral and genome-wide RNAi screens suggest that there are more clock genes to be identified. Using systems biology and mouse genetics approaches, we aim to understand the detailed molecular basis of transcriptional regulations on clock phase, amplitude, and period-length.

2.
Suprachiasmatic nucleus (SCN) is the clock master organ, located in the anterior hypothalamus. Previous studies indicated that the coupling mechanism distinguishes the SCN from other peripheral tissues in controlling the robustness of the clock. Using synthetic biology tools, we aim to reconstitute fibroblast cells, an exemplary model for peripheral clocks, into SCN neurons by transplanting the coupling system. A successful recapitulation of SCN properties by manipulating fibroblasts will not only offer mechanistic insights for the coupling, but also provide sufficient materials for biochemical characterization, allowing us to understand the uniqueness of clock master regulation.

3.
Metabolic disorders are linked to malfunctions of the circadian clock. To fully benefit from the PI’s expertise on high-throughput screening (HTS) and the “state-of-the-art” HTS facility at NIBS, we plan to conduct a few pilot/exploratory projects to understand the clock’s impacts on alcohol metabolism and fatty-liver development. Hypotheses generated from these cell-based screens will be further tested in vivo.



所有学术论文
https://scholar.google.com/citations?hl=en&user=x1V6G-gAAAAJ

发表文章（节选）
1.Ju, D.*, Zhang, W.*, Yan, J., Zhao, H., Li, W., Wang, J., Liao, M., Xu, Z., Wang, Z., Zhou, G., Mei, L., Hou, N., Ying, S., Cai, T., Chen, S., Xie, X., Lai, L., Tang, C., Park, N., Takahashi, J.S., Huang, N., Qi, X.?, andZhang, E.E.? Chemical Perturbations Reveal That RUVBL2 Regulates the Circadian Phase in Mammals. (2020)Science Translational Medicine12: eaba0769 {Featured by Editor in the issue: “Shifting clock gears”}
2.Han, K.*, Mei, L.*, Zhong, R., Pang, Y.,Zhang, E.E.?, and Huang Y.? A Microfluidic Approach for Experimentally Modeling the Intercellular Coupling System of a Mammalian Circadian Clock at Single-cell Level. (2020)Lab on a Chip20, 1204-1211
3.Peng, S.*, Xiao, W.*, Ju, D.*, Sun, B., Hou, N., Liu, Q., Wang, Y., Zhao, H., Gao, C., Zhang, S., Cao, R., Li, P., Huang, H., Ma, Y., Wang, Y., Lai, W., Ma, Z., Zhang, W., Huang, S., Wang, H., Zhang, Z., Zhao, L., Cai, T., Zhao, Y., Wang, F., Nie, Y., Zhi, G., Yang, Y.?,Zhang, E.E.?, and Huang, N.? Identification of Entacapone as a Chemical Inhibitor of FTO Mediating Metabolic Regulation Through FOXO1. (2019)Science Translational Medicine11: eaau7116 {Featured by Editor in the issue: “The skinny on FTO”}
4.Mei, L.*, Fan, Y., Lv, X., Welsh, D.K., Zhan, C.?, andZhang, E.E.?Long-termin vivoRecording of Circadian Rhythms in Brains of Freely Moving Mice. (2018)Proceedings of the National Academy of Sciences U.S.A.115: 4276-4281{Highlighted byFaculty of 1000(Very Good); Detailed protocol can be viewed in a video publication ofJOVE56765}
5.Wu, Y.*, Tang, D.*, Liu, N., Xiong, W., Huang, H., Li, Y., Ma, Z., Zhao, H., Chen, P., Qi, X., andZhang, E.E.? Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals. (2017)Cell Metabolism25: 73-85 {Cover story of the issue; Featured byScience Signaling, “Daily oxygen rhythms”(Editors' Choice)}
6.Zhang, E.E.* and Kay, S.A.? Clocks Not Winding Down: Unraveling Circadian Networks. (2010)Nature Reviews Molecular Cell Biology11: 764-776 {Invited Review,10-year Anniversary Series}
7.Zhang, E.E.*, Liu, Y.*, Dentin, R., Pongsawakul, P.Y., Liu, A.C., Hirota, T., Nusinow, D.A., Sun, X., Landais, S., Kodama, Y., Brenner, D., Montminy, M.? and Kay, S.A.? Cryptochrome Mediates Circadian Regulation of cAMP Signaling and Hepatic Gluconeogenesis. (2010)Nature Medicine16: 1152-1156 {Featured byNature Medicine, “High glucose, no cry” (News and Views); Highlighted byFaculty of 1000(Very Good)}
8.Zhang, E.E.*, Liu, A.C.*, Hirota, T.*, Miraglia, L.J., Welch, G., Pongsawakul, P.Y., Liu, X., Atwood, A., Huss, J.W.III., Janes, J., Su, A.I., Hogenesch, J.B.?, and Kay, S.A.? A Genome-wide siRNA Screen for Modifiers of the Circadian Clock in Human Cells. (2009)Cell139: 199-210 {Highlighted byFaculty of 1000(Exceptional)}


专利申请
1.Zhang, E., Qi, X., Ju, D., Zhou, G., Zhao, H., Mei, L., Wang, Z., and Liang, L. Nucleoside analogue regulating mammalian circadian rhythm. WIPO Publication # WOA1
2.Zhang, E., Zhan, C., and Mei, L. A method and instrumental design for long-term and real- time recording of gene transcriptions in live animals. NIPA Application# 20**


受邀会议报告
1.Society for Research on Biological RhythmsBiennial Meeting, Virtual Conference, May 30- June 3, 2020
2.10^thAnnual Symposium ofCenter for Circadian Biology, University of California San Diego, La Jolla, California, USA, March 4-6, 2020
3.Keystone Symposiaon "Hypoxia: Molecules, Mechanisms and Disease", Keystone, Colorado, USA, January 18-24, 2020 (Session Chair)
4.XVI Congress,European Biological Rhythm Society, Lyon, France, August 25-30, 2019
5.Sapporo Symposium on Biological Rhythms,Japanese Society for Chronobiology, Sapporo, Japan, July 11-16, 2018
6.Society for Research on Biological RhythmsBiennial Meeting, Amelia Island, Florida, USA, May 12-16, 2018
7.Gordon Research Conferenceon Chronobiology, Stowe, Vermont, USA, July 16-21, 2017
8.Cold Spring Harbor AsiaMeeting on Biological Rhythms, Suzhou, China, October 26-30, 2015 (Session Chair)



会议组织
1.Organizing Committee:5^thWorld Congress of Chronobiology(WCC), Suzhou, China, April 25-28, 2019
2.Co-organizer of two (with Dr. Qinghua Liu):1^stBeijing Symposium on the Circadian Clock and Sleep Research, Beijing, China, April 23-24, 2019
3.Co-organizer of two (with Dr. Jinhu Guo): Satellite symposium on "Biological Rhythms: Health & Adaptation",Chinese Society for Cell BiologyAnnual Meeting, Nanjing, China, April 11-12, 2018
4.Organizing Committee:2^ndAsian Forum on Chronobiology(AFC), Hohhot, Inner Mongolia, China, June 25-27, 2017
5.Co-organizer of three (with Drs. Ying Xu and Yi Rao):International ChronoBiology Summer School(CBS), Beijing, China, August 1-6, 2016



其它学术活动
1.Ad HocReviewer for Scientific Journals:Science, Nature Reviews Drug Discovery,Cell Metabolism,Journal of Clinical Investigation, PLoS Biology,Cell Research,iScience, Journal of Biological Rhythms, Scientific Reports,Trends in Endocrinology and Metabolism, Frontiers in Molecular Neuroscience / Pharmacology / Physiology,Brian Science Advances,etc.
2.Ad HocReviewer for Research Funding Agencies:National Natural Science Foundation of China(NSFC),Ministry of Science and Technology(MOST) of China,Agence Nationale de la Recherche(ANR) of France
3.Associate Editor:Frontiers in Molecular Neuroscience
4.Guest Associate Editor:Frontiers in Pharmacology
5.Founding Vice President (since 2015):Chinese Society for Biological Rhythms(CSBR)