Qinghua Liu, Ph.D.

Investigator, NIBS, Beijing, China

Phone: 86-10-80726688

Fax: 86-10-80726689

E-mail: liuqinghua@nibs.ac.cn

Education

2000 Ph. D. Department of Biochemistry, Baylor College of Medicine, USA

1992 B. S. Department of Biochemistry, Wuhan University, Wuhan, China

Professional Experience

2018-

Investigator,National Institute of Biological Sciences,Beijing, China

201304-202103

Professor，International Institute of Integrative Sleep Medicine (IIIS) University of Tsukuba, Japan

201009-201712

Tenured Associate Professor， University of Texas Southwestern Medical Center, USA

200406-201008

Assistant ProfessorUniversity of Texas Southwestern Medical Center, USA

200101-200405

Postdoctoral Fellow  University of Texas Southwestern Medical Center, USA

Research Description

Sleep exists ubiquitously from invertebrates to mammals. However, the precise functions and mechanisms of sleep remain one of the biggest “black boxes” in biology. We collaborated with Dr. Masashi Yanagisawa, who has conducted a EEG/EMG-based forward-genetics “sleep” screen to identify mutant mice with strong sleep abnormalities, such as Sleepy (SIK3, an AMPK-related protein kinase) and Dreamless (NALCN, a cation channel). We performed quantitative proteomic and phosphoproteomic comparison of Sleepy and sleep-deprived wild-type mouse brains, and identified 80 sleep need index phosphoproteins (SNIPPs), whose phosphorylation states change in relation to sleep need. Preferential association between SLEEPY and SNIPPs suggest that they are potentially substrates of SLEEPY/SIK3 kinase and downstream effectors of homeostatic sleep regulation. The majority (~86%) of SNIPPs are annotated synaptic proteins, suggesting a mechanistic link between synaptic phosphoproteome and sleep need regulation. On the other hand, emotions define the essence of being human and are powerful drivers of animal behaviors; For example, “mouse is afraid of cat” is a form of innate fear that is genetically encoded. In collaboration with Nobel laureate Dr. Bruce Beutler, we conducted the first forward-genetics “fear” screen to isolate “fearful” and “fearless” mutant mice. Among these, we discovered TRPA1 as a novel chemosensor for predator odor-evoked innate fear (e.g., freezing) behaviors and identified a novel brain region that mediates innate fear-associated hypothermia. Finally, we have recently developed a novel adult brain chimeric (ABC)-expression/knockout system for somatic genetics analysis in adult mice, which facilitates high-throughput screening of sleep/fear regulatory genes and elucidation of the molecular mechanisms of sleep and innate fear.

Publications

1. Shanshan Liu, Song Fu, Guodong Wang, Yu Cao, Lanlan Li, Xuemei Li, Jun Yang, Ning Li, Yabing Shan, Yang Cao, Yan Ma, Mengqiu Dong, Qinghua Liu, Hui Jiang*. Glycerol-3-Phosphate Biosynthesis Regenerates Cytosolic NAD+ to Alleviate Mitochondrial Disease, Cell Metabolism (2021)
2. Tomohiko Matsuo, Tomoko Isosaka, Yuichiro Hayashi, Lijun Tang, Akihiro Doi, Aiko Yasuda, Mikio Hayashi, Chia-Ying Lee, Liqin Cao, Natsumaro Kutsuna, Sachihiro Matsunaga, Takeshi Matsuda, Ikuko Yao, Mitsuyoshi Setou, Dai Kanagawa, Koichiro Higasa, Masahito Ikawa, Qinghua Liu*, Reiko Kobayakawa*, & Ko Kobayakawa*. Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation, Nature communications, 12, 1-17 (2021)
3. Can Liu, Chia-Ying Lee, Greg Asher, Liqin Cao, Yuka Terakoshi, Peng Cao, Reiko Kobayakawa, Ko Kobayakawa, Katsuyasu Sakurai*, Qinghua Liu*. Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia, Nature Communications，12,1-15 (2021)
4. Tingting Lou, Jing Ma, Zhiqiang Wang, Yuka Terakoshi, Chia-Ying Lee, Greg Asher, Liqin Cao, Zhiyu Chen, Katsuyasu Sakurai*, Qinghua Liu*. Hyper-Activation of mPFC Underlies Specific Traumatic Stress-Induced Sleep–Wake EEG Disturbances, Frontiers in Neuroscience, 14, 883 (2020)
5. 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, S. 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）
6. 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, 1-15 (2018）
7. 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)
8. H. Funato, et al., Q. Liu, K. Kume, S. Wakana, J.S. Takahashi, M.Yanagiaswa. Forward- genetics analysis of sleep in randomly mutagenized mice, Nature, 539, 378-383 (2016)
9. 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, Journal of Biological Chemistry, 289, 31950-31959 (2014)
10. 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-transcriptional microRNA processing. Molecular Cell, 63, 420-432, (2016)
11. C. Liang, Y. Wang, Y. Murota, X. Liu, D. Smith, MC. Siomi, Q. Liu. TAF11assembles RISC loading complex to enhance RNAi efficiency. Molecular Cell ，59，807-818 (2015)
12. Q. Liu and Z. Paroo, Biochemical and regulatory mechanisms of small RNA pathways. Annul Rev Biochem, 79, 295-320 (2010)
13. 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)
14. 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)
15. 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)
16. 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. Science，301，1921-1925 (2003)