基本信息
教育经历
工作经历
研究概述
发表文章

刘清华博士
北京生命科学研究所资深研究员
Qinghua Liu, Ph.D. Investigator, NIBS, Beijing, China
Phone: 86-

Fax: 86-

E-mail: liuqinghua@nibs.ac.cn



教育经历Education

2000 年理学博士美国贝勒医学院
2000 Ph.D. Department of Biochemistry, Baylor College of Medicine, USA

1992 年理学学士武汉大学生物化学系
1992 B.S. Department of Biochemistry, Wuhan University, Wuhan, China

工作经历Professional Experience

2018- 北京生命科学研究所资深研究员
2018- Investigator,National Institute of Biological Sciences,Beijing, China

2013- 教授日本筑波大学国际综合睡眠医学研究所
2013- Professor (World Premium Initiative), International Institute forIntegrative Sleep Medicine (IIIS), University of Tsukuba, Japan

2010 年- 终身副教授美国西南医学中心
2010- Associate Professor (tenured), W.A. “Tex” Moncrief Jr. Scholarin Medical Research, UT Southwestern Medical Center, USA

2004-2010 年助理教授美国西南医学中心
2004-2010 Assistant Professor, W.A. “Tex” Moncrief Jr. Scholar in MedicalResearch UT Southwestern Medical Center, USA

2004-2007 年研究员美国达蒙?鲁尼恩癌症研究基金会
2004-2007 Damon Runyon Scholar, Damon Runyon Cancer ResearchFoundation

2001-2004 年博士后美国西南医学中心/ 美国达蒙?鲁尼恩癌症研究会
2001-2004 Damon Runyon Postdoctoral Research Fellow, UT SouthwesternMedical Center, USA

研究概述

睡眠现象在动物中是普遍存在的，但睡眠的功能及其分子机理在生物学界中仍是一个巨大的未解之谜。 我们的合作者Masashi Yanagisawa博士利用基于脑电图-肌电图（EEG/EMG）的遗传学手段筛选鉴定出有明显睡眠异常的突变小鼠，如“嗜睡型”突变（突变基因是AMP激活的蛋白激酶SIK3）和“无梦型”突变（突变基因为钙离子通道NALCN）。我们已经开始利用质谱技术对嗜睡型突变小鼠和睡眠不足小鼠的大脑进行蛋白质组学和磷酸化蛋白质组学的定量比较。目前我们正在鉴定SIK3的生理学作用底物及其上游调节因子，并结合经典遗传学和生化手段探寻“睡眠需求”的分子机制。同时，我们还建立了一个高效平台，我们将通过大规模筛查化学或CRISPR诱变的突变小鼠找出睡眠相关的新型突变。另一方面，情绪是人类的根本特质之一，也是驱使我们行为产生的强大动力。最近我们开发了一套针对情绪的正向遗传筛查方法，能鉴定出“恐惧型”和“无惧型”突变小鼠。我们已研究发现了一条新的由捕食者气味诱导的自身恐惧应激通路。此外，我们也将进一步展开有关将 “恐惧型”突变小鼠用作遗传动物的模型，以研究人类焦虑情绪异常，从而开发出新的治疗方案的工作。
Research Description

Sleep exists ubiquitously from invertebrates to mammals. However, the precise functions and molecular mechanisms of sleep remain one of the biggest “black boxes” in biology. We collaborated with Dr. Masashi Yanagisawa, who has conducted a “tour-de-force” EEG/EMG-based forward genetic “sleep” screen to identify mutant mice with strong sleep abnormalities, such as Sleepy (SIK3, an AMP-activated protein kinase) and Dreamless (NALCN, a cation channel). We applied cutting edgemass spectrometric technology for quantitative proteomic and phosphoproteomic comparison of Sleepy and sleep-deprived mouse brains. We are identifying the physiological substrates and regulators of SIK3 and exploring the molecular basis of “sleep need” by combining classical genetics and biochemical approaches. We are also establishing a highly efficient platform for identifying novel sleep mutants’ through large-scale screening of chemically or CRISPR-mutagenized mice. On the other hand, emotions define the essence of being human and are powerful drivers of behaviors. And yet little is understood about the molecular bases of emotions. We recently developed the first forward genetic screen on emotions to identify “fearful” and “fearless” mutant mice. Our studies have revealed a novel sensory pathway for predator odor-induced innate fear responses. Furthermore, we will examine whether “fearful” mice can be used as genetic models to study human anxiety disorders and develop therapeutic treatments.


发表文章Publications

Z. Wang, J. Ma, C. Miyoshi, Y. Li, M. Sato, Y. Ogawa, T. Lou, C. Ma, X. Gao, C. Lee, T. Fujiyama, X. Yang, S. Zhou, N. Hotta-Hirashima, D. Klewe-Nebenius, A. Ikkyu, M. Kakizaki, S. Kanno, L. Cao, Satoru. Takahashi, J. Peng, Y. Yu, H. Funato, M. Yanagisawa & Q. Liu; Quantitative phosphoproteomic analysis of the molecular substrates of sleep need; Nature; 558,435–439（2018）
Y. Wang#, L. Cao#, CY. Lee, T. Matsuo, K. Wu, G. Asher, L. Tang, T. Saitoh, J. Russell, D. Klewe-Nebenius, L. Wang, S. Soya, E. Hasegawa, Y. Chérasse, J. Zhou, Y. Li, T. Wang, X. Zhan, C. Miyoshi, Y. Irukayama, J. Cao, JP. Meeks, L. Gautron, Z. Wang, K. Sakurai, H. Funato, T. Sakurai, M. Yanagisawa, H. Nagase, R. Kobayakawa, Ko Kobayakawa, B. Beutler & Q. Liu; Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors; Nature Communications; 9, 2041(2018）
K. L. Egerod, N. Petersen, P. N. Timshel, J. C. Rekling, Y. Wang, Q. Liu, T. W. Schwartz, L. Gautron. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms; MOLECULAR METABOLISM 12, 62-75(2018)
H. Funato, et al., Q. Liu, K. Kume, S. Wakana, J.S. Takahashi, M.Yanagiaswa. Forward- genetics analysis of sleep in randomlymutagenized mice Nature (Article), 539:378-383 (2017)
H. Liu, C. Liang, R.K. Kollipara, M. Matsui, X. Ke, B-C.Jeong, Z. Wang, K.S.Yoo, G.P. Yadav, L.N. Kinch, N.V. Grishin, Y. Nam, D.R. Corey, R. Kittler,Q.Liu. HP1BP3, a chromatin retention factor for co-transcriptionalmicroRNA processing. Molecular Cell 63:420-432. PMCID** (2016)
C. Liang, Y. Wang, Y. Murota, X. Liu, D. Smith, MC. Siomi, Q. Liu.TAF11assembles RISC loading complex to enhance RNAi efficiency. MolecularCell 59:807-818. PMCID**(2015)
J. Hanus, H. Zhang, DH. Chen, Q. Zhou, P. Jin, Q. Liu, S. Wang. Gossypol Acetic Acid Prevents Oxidative Stress-Induced Retinal Pigment Epithelial Necrosis by Regulating the FoxO3/Sestrin2 Pathway. Mol Cell Biol. 35:1952-63. PMCID**(2015)
Z. Wang, S. Liu, M. Kakizaki, Y. Hirose, Y. Ishikawa, H. Funato, M. Yanagisawa, Y. Yu, Q. Liu. Orexin/Hypocretin activates mTOR complex 1 (mTORC1) via an Erk/Akt-independent and calcium stimulated lysosome v-ATPase pathway. J BiolChem, 289: 31950-31959. PMCID**(2014)
MC. Llaguno, H. Xu, L. Shi, N. Huang, H. Zhang, Q. Liu, QX. Jiang. Chemically functionalized carbon films for single molecule imaging. J. Struc Biol. 185:405-417. PMCID** (2014)
Karamyshev AL, Patrick AE, Karamysheva ZN, Griesemer DS, Hudson H, Tjon-Kon-Sang S,Nilsson I, Otto H, Liu Q, Rospert S, von Heijne G, Johnson AE, Thomas PJ. Inefficient SRP interaction with a nascent chain triggers a mRNA quality control pathway. Cell 156: 146-157 (2014)
C. Liang, K. Xiong, K.E. Szulwuch, Y. Zhang, Z. Wang, J. Peng, M. Fu, P. Jing, H.I. Suzuki, Q. Liu. Sjogren Syndrome Antigen B (SSB)/La promotes global microRNA expression by binding microRNA precursors through stem-loop recognition. J BiolChem,288:723-36.1 PMCID** (2013)
Y. Li, L. Lin, Z. Li, X. Ye, K. Xiong, B. Aryal, Z. Xu, Z. Paroo, Q. Liu, C. He, P. Jin(2012) Iron Homeostasis Regulates the Activity of the MicroRNA Pathway through Poly(C)-Binding Protein 2. Cell Metabolism, 15:895-904 (2012)
Y. Liu, H. Tan, H.Tian, C. Liang, S. Chen, Q. Liu. Autoantigen La promotes RNAi, antiviral response, and transposon silencing by facilitating multiturnover RISC catalysis, Molecular Cell44:502-8 (2011)
X. Ye, N. Huang, Y. Liu, Z. Paroo, C. Huerta, P. Li, S. Chen, Q. Liu*, H. Zhang* (co-corresponding authors). Structure of C3PO and mechanism of human RISC activation. NatStructMol Biol.18:650-657 (2011)
N. Welker, T.S. Maity*, X. Ye*, P.J. Aruscavage, A.A. Krauchuk, Q. Liu, and B.L. Bass. Dicer's helicase domain discriminates dsRNA termini to promote an altered reaction mode. Molecular Cell 41: 589-599 (2011)
K. Okamura, N. Robine, Y. Liu, Q. Liu, and E.C. Lai. R2D2 organizes small regulatory RNA pathways in Drosophila. Mol Cell Biol 31:884-896. PMCID** (2011)
M. Yoda, T. Kawamata, Z. Paroo, X. Ye, S. Iwasaki, Q. Liu, and Y. Tomari. ATP-dependent human RISC assembly pathways.NatStructMolBiol 17:17-23.PMCID** (2010)
Q. Liu and Z. Paroo, Biochemical and regulatory mechanisms of small RNA pathways. Annul Rev Biochem. 79, 295-320 (2010)
Paroo, X. Ye, S. Chen, and Q. Liu. Phosphorylation of the human micro-RNA generating complex mediates MAPK/Erk signaling. Cell 139:112-122 (2009)
Y. Liu, X. Ye, F. Jiang, C. Liang, D. Chen, J. Peng, L.N. Kinch, N.V. Grishin, and Q. Liu. C3PO, an endoribonuclease that promotes RNAi by facilitating RISC activation.Science,325:750-753 (2009)
Shan G, Li Y, Zhang J, Li W, Szulwach KE, Duan R, Faghihi MA, Khalil AM, Lu L, Paroo Z, Chan AW, Shi Z, Liu Q, Wahlestedt C, He C, Jin P, A small molecule enhances RNA interference and promotes microRNA processing. Nat Biotechnol 26:933-940 (2008)
X. Ye, Z. Paroo, and Q. Liu, The functional anatomy of Drosophila microRNA-generating enzyme. J BiolChem 282: 28373-28378 (2007)
J. Park, X. Liu, T. Strauss, D. McKearin, and Q. Liu, The miRNA pathway intrinsically controls self-renewal of Drosophila germline stem cells. CurrBiol 17: 533–538(2007)
F. Jiang, X. Ye, X. Liu, L. Fincher, D. McKearin, Q. Liu, Dicer-1 and R3D1-L catalyze miRNA maturation in Drosophila. Genes Dev 19: 1674-1679 (2005)
M. L. Lam, Q. Liu, S. J. Elledge, J. M. Rosen, Haplo-insufficency for Chk1 results in a damage S phase and cell cycle mis-coordination during development. Cancer Cell 6:45-59 (2004).
Q. Liu, T. A. Rand, S. Kalidas, F. Du, H. Kim, D.P. Smith, X. Wang, R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science301:1921-1925. (2003)
Q. Liu et al., Chk1 is an essential kinase that is regulated by Atr and required for the G2/M DNA damage checkpoint. Genes Dev 14: 1448-1459 (2000)
Q. Liu, M. Z. Li, D. Liebham, D. Cortez, S. J. Elledge, The univector plasmid-fusion system, a method for rapid construction of recombinant DNA without restriction enzymes. CurrBiol 8:1300-1309 (1998)
Y. Sanchez, B. A. Desany, W. J. Jones, Q. Liu, B. Wang, S. J. Elledge, Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Science 271: 357-360 (1996)