师资队伍
各类人才
研究生导师
课题组长（PI）
首席教师
李乾
  作者：  2021-04-02

 基本信息 >>>

undefined李乾，博士，Qian Li，Ph.D.

嗅觉系统发育及相关疾病研究组

Laboratory Of Olfactory Physiology and Pathology (LOOP)

Shanghai Jiao Tong University School of Medicine

电话（Tel）：63846590-776985

邮箱（Email）：liqian@shsmu.edu.cn

研究方向>>>

本实验室主要以小鼠嗅觉系统为模型，通过分子生物学、影像学、行为学、多组学等研究手段结合基因敲除、转基因小鼠模型，研究嗅觉系统发育过程中神经元的分化、嗅觉受体基因转录的分子机制，以及嗅觉发育障碍与情绪及学习记忆相互作用的环路基础。具体的研究方向如下：

 

1. 以嗅觉神经元中嗅觉受体基因选择为模型，研究表观遗传和三维基因组调控的分子机制

我们以嗅觉系统为模型，研究表观遗传和基因组三维构象决定特异嗅觉神经元亚型的分子机制。嗅觉神经元中表达的嗅觉受体在识别外界气味信息和神经元投射中都起了非常重要的作用，嗅觉受体的转录表达便是嗅觉神经元发育的中心事件。虽然小鼠有约1100种嗅觉受体基因，但每个嗅觉神经元只表达其中一种嗅觉受体，这种精确的表达模式提供了一个非常好的系统来研究基因转录调控机制。在前期研究中，我们发现了两个新的增强子，能特异调控一类非经典的嗅觉受体基因。在后期工作中，我们拟进一步研究增强子、抑制子和绝缘子等调控嗅觉受体基因转录的分子机制，并鉴定增强子或抑制子在特定嗅觉神经元中形成的三维结构图谱。

2. 嗅觉干细胞分化成特异嗅觉神经元亚群的分子细胞机制

嗅觉神经元由于直接接触外界环境中的气味分子而非常敏感，平均每个嗅觉神经元能存活30-90天，死去的嗅觉神经元便会被新生的嗅觉神经元所取代。新生的嗅觉神经元是嗅觉干细胞分化来的，但是嗅觉神经元根据其表达的嗅觉受体类型拥有不同的亚群，而嗅觉干细胞分化成特定嗅觉神经元亚群的具体信号通路以及分子机制依然未知。我们前期已构建了标记不同嗅觉神经元亚群的转基因小鼠，进一步将通过全基因组CRISPR-Cas9筛选，获得关键的调控元件和信号分子，并解析其作用机理。研究嗅觉干细胞的分化机制将为治疗嗅觉障碍的病人(大约5%的人群)提供新的思路和药物靶点。

3. 嗅觉发育异常与情绪及学习记忆的互作环路基础

嗅觉障碍病人除了在嗅闻气味方面存在障碍之外，还具有情绪和学习记忆方面的问题，但是其因果关系及其环路基础仍然未知。我们已构建了嗅觉特异损伤的转基因小鼠，拟解析其与情绪及学习记忆障碍的关联性，及其相互作用的环路基础。

个人简历 >>>

李乾研究员，博士生导师。2004年本科毕业于中国科学技术大学，2009年博士毕业于中国科学院生物化学与细胞生物学研究所，2010-2016年在美国哈佛大学从事博士后工作，并于2016年加入上海交通大学医学院基础医学院，担任“嗅觉系统发育及相关疾病”研究员组组长。主要工作以通讯或第一作者（包含共同）发表于Nature、Cell、Nature Communications、Molecular Biology and Evolution、Molecular Systems Biology、Current Biology、PNAS、eLife和Cell Reports等国际期刊。

论文与专著 >>>

代表性论文：（#co-first author, *corresponding/co-corresponding author）

1. Bao, Hongqiang#; Liu, Rong#; Kong, Yalei#; Liu, Penglai#; Kahiapo, Jerome#; Qian, Kangying; Li, Anan*; Tan, Longzhi*; Li, Qian*. “An epigenetic repressor TRIM66 dictates monogenic olfactory receptor expression, neural activity, and olfactory behavior”. Nature Communications, 2025, 16(1):11091.

2. Li, Qian*; Pan, Yufeng*; Tong, Xia-Jing*. “Sexual dimorphism in pheromone perception across worms, flies, and rodents”. Trends in Neurosciences, 2025, 48(12):1009-1022.

3. Hao, Yue; Wang, Zheng*; Li, Qian*. “Modulation of olfactory bulb activity by serotoninergic inputs in odor-associative learning”. Acta Physiologica, 2024, 27:e14222.

4. Hao, Yue#; Qian, Kang-Ying#; Li, Qian*. “A noncoding role of coding mRNA in monogenic olfactory receptor choice”. Trends in Neurosciences, 2024, 47(3):167-169.

5. Shang, Pan#; Rong, Naikang#; Jiang, Jing-Jing#; Cheng, Jie#; Zhang, Ming-Hui#; Kang, Dongwei#; Qi, Lei#; Guo, Lulu; Yang, Gong-Ming; Liu, Qun; Zhou, Zhenzhen; Li, Xiao-Bing; Zhu, Kong-Kai; Meng, Qing-Biao; Han, Xiang; Yan, Wenqi; Kong, Yalei; Yang, Lejin; Wang, Xiaohui; Lei, Dapeng; Feng, Xin; Liu, Xinyong; Yu, Xiao; Wang, Yue*; Li, Qian*; Shao, Zhen-Hua*; Yang, Fan*; Sun, Jin-Peng*. “Structural and signaling mechanisms of TAAR1 enabled preferential agonist design”. Cell, 2023, 186(24):5347-5362.e24.

6. Guo, Lulu#; Cheng, Jie#; Lian, Shuo#; Liu, Qun#; Lu, Yan#; Zheng, Yuan#; Zhu, Kongkai#; Zhang, Minghui;Kong, Yalei; Zhang, Chao; Rong, Naikang; Zhuang, Yuming; Fang, Guoxing; Jiang, Jingjing; Zhang, Tianyao;Han, Xiang; Liu, Zili; Xia, Ming; Liu, Shangming; Zhang, Lei; Liberles, Stephen D; Yu, Xiao; Xu, Yunfei*; Yang, Fan*; Li, Qian*; Sun, Jin-Peng*. “Structural basis of amine odorant perception by a mammal olfactory receptor”. Nature, 2023, 618(7963):193.

7. Guo, Lingna#; Dai, Wenxuan#; Xu, Zhengrong#; Liang, Qiaoyi; Miller, Eliot T; Li, Shengju; Gao, Xia; Baldwin, Maude W; Chai, Renjie*; Li, Qian*. “Evolution of brain-expressed biogenic amine receptors into olfactory trace amine-associated receptors”. Molecular Biology and Evolution, 2022, 39(3):msac006.

8. Zhou, Haiqian#; Zhuang, Liujing#; Bao, Hongqiang#; Li, Shengju; Dai, Fengyan; Wang, Ping; Li, Qian*; Yin, Dongmin*. “Olfactory regulation by dopamine and DRD2 receptor in the nose”. PNAS, 2022, 119(11):e2118570119.

9. Song, Chunxue; Zeng, Xianting; Zeng, Wanxin; Liu, Rong; Tong, Xiajing*; Li, Qian*. “A WDR47 homolog facilitates ciliogenesis by modulating intraflagellar transport”. Journal of Cell Science, 2022, 135(24):jcs260303.

10. Zhang, Qianwen#; Ding, Yu#; Feng, Biyun; Tang, Yijun; Chen, Yao; Wang, Yirou; Chang, Guoying; Liu, Shijian; Wang, Jian; Li, Qian*; Fu, Lijun*; Wang, Xiumin*. “Molecular and phenotypic expansion of Alström syndrome in Chinese patients”. Frontiers in Genetics, 2022, 13:808919.

11. Xu, ZhengRong#; Guo, LingNa#; Qian, XiaoYun#; Yu, ChenJie#; Li, ShengJu; Zhu, ChengWen; Ma, XiaoFeng; Li, Hui; Zhu, GuangJie; Zhou, Han; Dai, WenXuan*; Li, Qian*; Gao, Xia*. “Two entry tunnels in mouse TAAR9 suggest the possibility of multi-entry tunnels in olfactory receptors”. Scientific Reports, 2022, 12(1):2691.

12. Fei, Aimei#; Wu, Wanqing#; Tan, Longzhi#; Tang, Cheng#; Xu, Zhengrong; Huo, Xiaona; Bao, Hongqiang; Johnson, Mark; Hartmann, Griffin; Talay, Mustafa; Yang, Cheng; Riegler, Clemens; Joseph, Kristian; Engert, Florian; Xie, X Sunney; Barnea, Gilad; Liberles, Stephen D; Yang, Hui; Li, Qian*. “Coordination of two enhancers drives expression of olfactory trace amine-associated receptors”. Nature Communications, 2021, 12(1): 3798.

13. Qian, Kang-Ying; Zeng, Wan-Xin; Hao, Yue; Zeng, Xian-Ting; Liu, Haowen; Li, Lei; Chen, Lili; Tian, Fu-Min; Chang, Cindy; Hall, Qi; Song, Chun-Xue; Gao, Shangbang; Hu, Zhi-Tao; Kaplan, Josh M; Li, Qian*; Tong, Xia-Jing*. “Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner”. eLife, 2021, 10: e67170.

14. Jia, Liang#; Li, Shengju#; Dai, Wenxuan; Guo, Lingna; Xu, Zhengrong; Scott, Anne M; Zhang, Zhe; Ren, Jianfeng; Zhang, Qinghua; Dexheimer, Thomas S; Chung-Davidson, Yu-Wen; Neubig, Richard R*; Li, Qian*; Li, Weiming*. “Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site”. Journal of Biological Chemistry, 2021, 297(5): 101268.

15. Gan, Linhua#; Sun, Jingjing#; Yang, Shuo; Zhang, Xiaocui; Chen, Wu; Sun, Yiyu; Wu, Xiaohua; Cheng, Cheng; Yuan, Jing; Li, Anan; Corbett, Mark A.; Dixon, Mathew P.; Thomas, Tim; Voss, Anne K.; Gecz, Jozef; Wang, Guang-Zhong; Bonni, Azad; Li, Qian*; Huang, Ju*. “Chromatin-binding protein PHF6 regulates activity-dependent transcriptional networks to promote hunger response”. Cell Reports, 2020, 30(11): 3717-3728.e6.

16. Xu, Zhengrong; Li, Qian*. “TAAR agonists”. Cellular and Molecular Neurobiology, 2020, 40(2): 257-272.

17. Tan, Longzhi#; Li, Qian#; Xie, X Sunney*. “Olfactory sensory neurons transiently express multiple olfactory receptors during development”. Molecular Systems Biology, 2015, 11(12): 844. (Highlighted in Nature Chemical Biology)

18. Li, Qian; Tachie, Baffour Yaw; Liu, Zhikai; Baldwin, Maude W; Kruse, Andrew C; Liberles, Stephen D*. “Non-classical amine recognition evolved in a large clade of olfactory receptors”. eLife, 2015, 4: e10441.

19. Li, Qian; Liberles, Stephen D*. “Aversion and attraction through olfaction”. Current Biology, 2015, 25(3): 120-129.

20. Li, Qian; Korzan, Wayne J; Ferrero, David M; Chang, Rui B; Roy, Dheeraj S; Buchi, Melanie; Lemon, Jamie K; Kaur, Angeldeep W; Stowers, Lisa; Fendt, Markus; Liberles, Stephen D*. “Synchronous evolution of an odor biosynthesis pathway and behavioral response”. Current Biology, 2013, 23(1): 11-20. (Commented in Current Biology)

21. Li, Qian; Su, Yuan Yuan; Wang, Hao; Li, Lei; Wang, Qiong; Bao, Lan*. “Transmembrane segments prevent surface expression of sodium channel Na(v)1.8 and promote calnexin-dependent channel degradation”. Journal of Biological Chemistry, 2010, 285(43): 32977-32987.

22. Zhang, Zhen Ning#; Li, Qian#; Liu, Chao; Wang, Hai Bo; Wang, Qiong; Bao, Lan*. “The voltage-gated Na(+) channel Na(v)1.8 contains an ER-retention/retrieval signal antagonized by the beta 3 subunit”. Journal of Cell Science, 2008, 121(19): 3243-3252.