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清华大学生物医学交叉研究院 TIMBR, Tsinghua University
长聘教授,资深研究员
刘清华研究员是目前国际睡眠领域的领衔专家,1992年毕业于武汉大学,2000年于美国贝勒医学院获得PhD学位,随后在美国德州大学西南医学中心王晓东院士实验室任进行博士后训练,2010年获得美国德州大学西南医学中心终身教授身份,2013年担任日本筑波大学国际综合睡眠医学研究所教授,并于2018年至今担任北京生命科学研究所资深研究员。刘清华研究员在哺乳动物睡眠调控的分子遗传机制方面颇有建树,独创小鼠体细胞遗传学睡眠筛选平台,发现转录调控睡眠时长的首个信号通路,揭示突触蛋白磷酸化与睡眠需求调节机制的联系。此外,刘清华研究员与诺奖获得者Bruce Beutler合作,在小鼠中开展了首个先天性恐惧行为的正向遗传学筛选,发现了感知捕食者气味的新型传感器TRPA1,并揭示调控恐惧诱导体温下降的新脑区和神经环路机制。刘清华研究员在Nature,Science,Cell等国际顶级期刊上多次发表文章,为人类脑科学睡眠领域做出了重大贡献。
报告题目:
揭开睡眠之谜–睡眠时长是如何调控的?
Towards the mystery of sleep–How is sleep amount regulated?
报告摘要:
不同哺乳动物睡眠时长差异很大,从长颈鹿每天只睡2-5小时,到考拉熊每天睡18-22小时,调控睡眠时长的核心分子通路仍不清楚。我们最近发现了首个调控小鼠睡眠时长的分子通路 LKB1-SIK3-HDAC4/5-CREB,并提出转录调控睡眠时长的新机制。敲除AMPK家族上游蛋白激酶LKB1,显著降低NREMS时长和深度。敲除或过表达LKB1-SIK3下游底物HDAC4/5,可双向改变NREMS时长和深度。HDAC4/5的磷酸化变化和睡眠需求在睡眠/觉醒中的消长相对应,并且HDAC4/5在下丘脑后部调控睡眠时长。遗传和转录组分析表明,HDAC4与CREB形成复合体协同调控转录和睡眠。此研究提出了信号通路靶向转录因子调控睡眠时间的概念,并展示了体细胞遗传学将会有力促进小鼠睡眠研究。
Different mammals vary widely in daily sleep quotas, ranging from 2 to 5-h in giraffes to 18 to 22-h in koalas, reflective of a specific homeostasis between sleep and wakefulness in each species. In mice and humans, sleep quantity/quality of individuals are governed by genetic factors and exhibit age-dependent variations. However, the core molecular pathways and effector mechanisms that regulate sleep need in mammals remain unclear. Here, we characterize a major signaling pathway for transcriptional regulation of sleep need in mice by adeno-associated virus-mediated somatic genetics analysis. Adult brain chimeric (ABC)-knockout of LKB1 kinase, an activator of AMPK-related protein kinase SIK3, markedly reduces non-rapid eye movement sleep (NREMS) amount and delta power–a measure of sleep quality. Downstream of LKB1-SIK3, gain/loss-of-function of histone deacetylases HDAC4/5 causes bidirectional changes of NREMS amount and delta power. Phosphorylation of HDAC4/5 is regulated in relation to sleep need, and HDAC4 specifically regulate sleep amount in hypothalamic neurons. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signaling pathways targeting transcription modulators to regulate sleep amount and demonstrate the power of somatic genetics in mouse sleep research.
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刘清华研究员是目前国际睡眠领域的领衔专家,1992年毕业于武汉大学,2000年于美国贝勒医学院获得PhD学位,随后在美国德州大学西南医学中心王晓东院士实验室任进行博士后训练,2010年获得美国德州大学西南医学中心终身教授身份,2013年担任日本筑波大学国际综合睡眠医学研究所教授,并于2018年至今担任北京生命科学研究所资深研究员。刘清华研究员在哺乳动物睡眠调控的分子遗传机制方面颇有建树,独创小鼠体细胞遗传学睡眠筛选平台,发现转录调控睡眠时长的首个信号通路,揭示突触蛋白磷酸化与睡眠需求调节机制的联系。此外,刘清华研究员与诺奖获得者Bruce Beutler合作,在小鼠中开展了首个先天性恐惧行为的正向遗传学筛选,发现了感知捕食者气味的新型传感器TRPA1,并揭示调控恐惧诱导体温下降的新脑区和神经环路机制。刘清华研究员在Nature,Science,Cell等国际顶级期刊上多次发表文章,为人类脑科学睡眠领域做出了重大贡献。
报告题目:
揭开睡眠之谜–睡眠时长是如何调控的?
Towards the mystery of sleep–How is sleep amount regulated?
报告摘要:
不同哺乳动物睡眠时长差异很大,从长颈鹿每天只睡2-5小时,到考拉熊每天睡18-22小时,调控睡眠时长的核心分子通路仍不清楚。我们最近发现了首个调控小鼠睡眠时长的分子通路 LKB1-SIK3-HDAC4/5-CREB,并提出转录调控睡眠时长的新机制。敲除AMPK家族上游蛋白激酶LKB1,显著降低NREMS时长和深度。敲除或过表达LKB1-SIK3下游底物HDAC4/5,可双向改变NREMS时长和深度。HDAC4/5的磷酸化变化和睡眠需求在睡眠/觉醒中的消长相对应,并且HDAC4/5在下丘脑后部调控睡眠时长。遗传和转录组分析表明,HDAC4与CREB形成复合体协同调控转录和睡眠。此研究提出了信号通路靶向转录因子调控睡眠时间的概念,并展示了体细胞遗传学将会有力促进小鼠睡眠研究。
Different mammals vary widely in daily sleep quotas, ranging from 2 to 5-h in giraffes to 18 to 22-h in koalas, reflective of a specific homeostasis between sleep and wakefulness in each species. In mice and humans, sleep quantity/quality of individuals are governed by genetic factors and exhibit age-dependent variations. However, the core molecular pathways and effector mechanisms that regulate sleep need in mammals remain unclear. Here, we characterize a major signaling pathway for transcriptional regulation of sleep need in mice by adeno-associated virus-mediated somatic genetics analysis. Adult brain chimeric (ABC)-knockout of LKB1 kinase, an activator of AMPK-related protein kinase SIK3, markedly reduces non-rapid eye movement sleep (NREMS) amount and delta power–a measure of sleep quality. Downstream of LKB1-SIK3, gain/loss-of-function of histone deacetylases HDAC4/5 causes bidirectional changes of NREMS amount and delta power. Phosphorylation of HDAC4/5 is regulated in relation to sleep need, and HDAC4 specifically regulate sleep amount in hypothalamic neurons. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signaling pathways targeting transcription modulators to regulate sleep amount and demonstrate the power of somatic genetics in mouse sleep research.