演讲嘉宾

王晗


苏州大学 教授

王晗,博士,博士生导师,苏州大学生物钟研究中心主任。获美国韦恩州立大学博士学位;曾在美国佐治亚医学院和俄勒冈大学从事博士后研究;曾任美国俄克拉荷马大学助理教授(Assistant Professor)。目前任苏州大学特聘教授、江苏特聘教授、江苏省生物钟研究创新团队领军人才、国家重大科学研究计划生物钟研究项目首席科学家、国际时间生物学会(International Society of Chronobiology)理事、《Chronobiology International》杂志编委、中国中西医结合学会时间生物医学专业委员会主任,中国睡眠研究会理事, 中国睡眠研究会睡眠节律专业委员会副主任和中国斑马鱼研究会常务理事。

会议报告摘要:生物钟在神经疾病注意力缺陷多动症和抑郁症中的调控机制

The circadian clock as an endogenous time-keeping mechanism modulates fundamental life processes from molecular, biochemical, cellular, physiological to behavioral with a period of approximately 24 hours. Previous studies showed that circadian misalignment often lead to human psychiatric disorders such as seasonal affective disease (SAD). The underlying mechanisms, however, are far from certain. We found that zebrafish per1b mutants display hyperactive-, impulsive-, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human Attention Deficit Hyperactivity Disorder (ADHD) patients. Per1b directly regulates dopamine-related genes mao and dbh, and acts through genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. Here we show that zebrafish per2 mutant fish display lower locomotor activities, more time staying in the center region of the tank, less time for social interaction, reduced sleep time, and disrupted sleep continuity in comparison with wild types, indicating a clear depression phenotype of the per2 mutant zebrafish. Further, cortisol, and expression of pomc (proopiomelanocortin) and crh (corticotropin releasing hormone) are significantly up-regulated in the per2 mutant male fish, reminiscent of human depression patients with disruptive activities of the hypothalamic-pituitary-adrenal (HPA) axis. Quantitative RT-PCR shows that glucocorticoid receptor (gr) is significantly down-regulated in both the per2 mutant fish. Luciferase reporter assays show that Per2 can enhance Rorαa-mediated expression of gr, and ChIP assays show that Per2 binds to the three RORE elements in the gr promoter, suggesting that Per2 positively regulates gr in zebrafish. Our findings demonstrate that Per2 acts through glucocorticoid receptor signaling to impact functions of the hypothalamic-pituitary-adrenal (HPA) axis and to contribute to depression pathogenesis. Taken together, our analyses of zebrafish circadian mutants shed light on new roles of the circadian clock in psychiatric disorders.

研究方向

主要研究方向为斑马鱼生物钟和睡眠分子遗传和基因组调控机制、生物钟对生殖和发育的影响、生物钟调节演化机制等。发现了生物钟调控注意力缺陷多动症(ADHD) 的新机制、Period2 在生物钟调节环路中的双重作用机制以及Rev-erbα对自噬的直接调节机制;阐明了斑马鱼生物钟基因clock、bmal、per 和cry 等的分子演化机制;建立了斑马鱼生物钟基因全套突变体库。已在在Nature Genetics、Autophagy、 Journal of Neuroscience、Journal of Biological Chemistry、Development、Journal of Pineal Research 等杂志发表60 余篇学术论文。

生物360精选了王晗教授在2015-2016年发表的3篇文章,翻译摘要以供读者更好的了解其工作成果,详情访问

研究经历

1980-1984,安徽大学,学士。
1984-1987,中国科学院,硕士。
1991-1996,美国密执安州韦恩州立大学,博士。
1996-1998,美国佐治亚医学院分子医学遗传研究所斑马鱼分子遗传学实验室,博士后。
1998-2003,美国俄勒冈大学神经科学研究所斑马鱼遗传学实验室,博士后。
2003-2009,美国俄克拉荷马大学助理教授,斑马鱼遗传学和基因组学实验室主任。
2009-至今,苏州大学医学部基础医学与生物科学学院特聘教授。
2011-至今,苏州大学生物钟研究中心主任。
2011-至今,江苏省特聘教授。
2012-至今,国家重大科学研究计划(973)项目首席科学家。


近期发表论文

  1. Pengfei Niu, Zhaomin Zhong, Mingyong Wang, Guodong Huang, Shuhao Xu, Yi Hou, Yilin Yan, Han Wang: Zinc finger transcription factor Sp7/Osterix acts on bone formation and regulates col10a1a expression in zebrafish. DOI:10.1016/j.scib.2017.01.009
  2. Siran Pei, Li Liu, Zhaomin Zhong, Han Wang, Shuo Lin, Jing Shang: Risk of prenatal depression and stress treatment: Alteration on serotonin system of offspring through exposure to Fluoxetine. Scientific Reports 10/2016; 6., DOI:10.1038/srep33822
  3. Guocun Huang, Yunfeng Zhang, Yongli Shan, Shuzhang Yang, Yogarany Chelliah, Han Wang, Joseph S Takahashi: Circadian Oscillations of NADH Redox State Using a Heterologous Metabolic Sensor in Mammalian Cells. Journal of Biological Chemistry 09/2016; 291(46)., DOI:10.1074/jbc.M116.728774
  4. Ingo Braasch, Andrew R Gehrke, Jeramiah J Smith, Kazuhiko Kawasaki, Tereza Manousaki, Jeremy Pasquier, Angel Amores, Thomas Desvignes, Peter Batzel, Julian Catchen, Aaron M Berlin, Michael S Campbell, Daniel Barrell, Kyle J Martin, John F Mulley, Vydianathan Ravi, Alison P Lee, Tetsuya Nakamura, Domitille Chalopin, Shaohua Fan, Dustin Wcisel, Cristian Cañestro, Jason Sydes, Felix E G Beaudry, Yi Sun, Jana Hertel, Michael J Beam, Mario Fasold, Mikio Ishiyama, Jeremy Johnson, Steffi Kehr, Marcia Lara, John H Letaw, Gary W Litman, Ronda T Litman, Masato Mikami, Tatsuya Ota, Nil Ratan Saha, Louise Williams, Peter F Stadler, Han Wang, John S Taylor, Quenton Fontenot, Allyse Ferrara, Stephen M J Searle, Bronwen Aken, Mark Yandell, Igor Schneider, Jeffrey A Yoder, Jean-Nicolas Volff, Axel Meyer, Chris T Amemiya, Byrappa Venkatesh, Peter W H Holland, Yann Guiguen, Julien Bobe, Neil H Shubin, Federica Di Palma, Jessica Alfo¨ldi, Kerstin Lindblad-Toh, John H Postlethwait: Corrigendum: The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons. Nature Genetics 05/2016; 48(6):700-700., DOI:10.1038/ng0616-700c
  5. Guodong Huang, Fanmiao Zhang, Qiang Ye, Han Wang: The circadian clock regulates autophagy directly through the nuclear hormone receptor Nr1d1/Rev-erbα and indirectly via Cebpb/(C/ebpβ) in zebrafish. Autophagy 05/2016; 12(8)., DOI:10.1080/15548627.2016.1183843
  6. Zhaomin Zhong, Pengfei Niu, Mingyong Wang, Guodong Huang, Shuhao Xu, Yi Sun, Xiaona Xu, Yi Hou, Xiaowen Sun, Yilin Yan, Han Wang: Targeted disruption of sp7 and myostatin with CRISPR-Cas9 results in severe bone defects and more muscular cells in common carp. Scientific Reports 03/2016; 6:22953., DOI:10.1038/srep22953
  7. Da-long Ren, Ya-juan Li, Bing-bing Hu, Han Wang, Bing Hu: Melatonin regulates the rhythmic migration of neutrophils in live zebrafish. Journal of Pineal Research 03/2015; 58(4):n/a-n/a., DOI:10.1111/jpi.12230
  8. Jian Huang, Zhaomin Zhong, Mingyong Wang, Xifeng Chen, Yicheng Tan, Shuqing Zhang, Wei He, Xiong He, Guodong Huang, Haiping Lu, Ping Wu, Yi Che, Yi-Lin Yan, John H Postlethwait, Wenbiao Chen, Han Wang: Circadian Modulation of Dopamine Levels and Dopaminergic Neuron Development Contributes to Attention Deficiency and Hyperactive Behavior. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 02/2015; 35(6):2572-87., DOI:10.1523/JNEUROSCI.2551-14.2015
  9. Chao Liu, Jia Hu, Chunxiang Qu, Lin Wang, Guodong Huang, Pengfei Niu, Zhaomin Zhong, Fashui Hong, Guanghui Wang, John H. Postlethwait, Han Wang: Molecular evolution and functional divergence of zebrafish (Danio rerio) cryptochrome genes. Scientific Reports 01/2015; 5., DOI:10.1038/srep08113
  10. Mingyong Wang, Zhaomin Zhong, Yingbin Zhong, Wei Zhang, Han Wang: The Zebrafish Period2 Protein Positively Regulates the Circadian Clock through Mediation of Retinoic Acid Receptor (RAR)-related Orphan Receptor α (Rorα). Journal of Biological Chemistry 12/2014; 290(7):4367–4382., DOI:10.1074/jbc.M114.605022
  11. Shuqing Zhang, Minrui Xu, Jian Huang, Lili Tang, Yanqing Zhang, Jingyao Wu, Shuo Lin, Han Wang: Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish. Disease Models and Mechanisms 03/2014; 7(7)., DOI:10.1242/dmm.014951