李雷上岗副研究员
地址：西汉姆联江北校区汇川楼B座202室
教育和工作经历：
2025-12 至今, 西汉姆联, bw必威西汉姆联, 上岗副研究员
2024-09 至 2025-11, City University of Hong Kong/香港城市大学，Department of Neuroscience, 博士后
2015-07 至 2024-07, The University of Queensland/昆士兰大学 ,Queensland Brain Institute, 博士后
2009-09 至 2015-03, 华中科技大学, 生物物理, 博士
2005-09 至 2009-06, 华中科技大学, 生物信息学, 学士
研究方向与目标 (Research Interests)：
本课题组致力于阐明神经突触传递的分子机制，旨在揭示神经信号在神经元间高效、精确传递的底层规律，及其在神经系统疾病中的致病机理。课题组以秀丽隐杆线虫（C. elegans）为主要模式生物，综合运用分子遗传学、电生理记录及高分辨成像等技术，系统解析突触前囊泡释放、Ca²⁺通道调控、突触后受体定位及膜循环机制。
课题组前期围绕 UNC-13、突触结合蛋白（Synaptotagmin）及 CASK/FARP 等关键分子取得了一系列创新成果，深化了对突触可塑性和膜转运调控的认识。相关研究成果以第一或共同第一作者发表于 eLife (2025, 2019)、Structure (2023)、PLOS Genet (2022)、J Cell Biol (2021)、Cell Rep (2021, 2019, 2018)、J Neurosci (2018) 及 PNAS (2014) 等国际权威学术期刊共 13 篇。
未来，课题组将继续深耕突触功能与神经疾病发病机制，重点开展以下四个方向的研究：
1. 突触前囊泡释放与动力学调控：解析突触核心蛋白及钙离子感受蛋白对自发与诱发神经递质释放的精准调控机制。
2. 突触后受体定位与膜转运机制：揭示支架蛋白在调节受体跨膜转运、动态分布网络及突触可塑性中的核心功能。
3. 神经系统兴奋性与抑制性平衡 (E/I Balance)：探究突触蛋白在兴奋性与抑制性突触中的差异化调控机制，阐明 E/I 失衡的分子根源。
4. 疾病发病机制与药物筛选：结合自闭症、神经退行性疾病等动物模型，解析致病基因的突触损伤机制；并开展药物筛选，挖掘可改善突触功能、延缓神经元衰老的潜在临床治疗化合物。
代表性论文：
1. H. Liu*, L. Li*, J. Wang, J. Hu, J. Xia, X. Yu, J. Tang, H. Liu, X. Yang, C. Ma, L. Kang, Z. Hu, Mechanisms that regulate the C1-C2B mutual inhibition control functional switch of UNC-13. eLife14, RP105199 (2025).
2. L. Zhang*, L. Li*, Z. Wei, H*. Zhou, H. Liu, S. Wang, Y. Ren, T. Dai, J. Wang, Z. Hu, C. Ma, The C2 and PH domains of CAPS constitute an effective PI(4,5)P2-binding unit essential for Ca2+-regulated exocytosis. Structure31, 424-434.e6 (2023).
3. W.-X. Zeng, H. Liu, Y. Hao, K.-Y. Qian, F.-M. Tian, L. Li, B. Yu, X.-T. Zeng, S. Gao, Z. Hu, X.-J. Tong, CaMKII mediates sexually dimorphic synaptic transmission at neuromuscular junctions in C. elegans. J. Cell Biol.222, e202301117 (2023).
4. Y. Hao, H. Liu, X.-T. Zeng, Y. Wang, W.-X. Zeng, K.-Y. Qian, L. Li, M.-X. Chi, S. Gao, Z. Hu, X.-J. Tong, UNC-43/CaMKII-triggered anterograde signals recruit GABAARs to mediate inhibitory synaptic transmission and plasticity at C. elegans NMJs. Nat. Commun.14, 1436 (2023).
5. L. Li*, H. Liu*, K.-Y. Qian*, S. Nurrish*, X.-T. Zeng, W.-X. Zeng, J. Wang, J. M. Kaplan, X.-J. Tong, Z. Hu, CASK and FARP localize two classes of post-synaptic ACh receptors thereby promoting cholinergic transmission. PLoS Genet.18, e1010211 (2022).
6. K.-Y. Qian, W.-X. Zeng, Y. Hao, X.-T. Zeng, H. Liu, L. Li, L. Chen, F.-M. Tian, C. Chang, Q. Hall, C.-X. Song, S. Gao, Z. Hu, J. M. Kaplan, Q. Li, X.-J. Tong, Male pheromones modulate synaptic transmission at the C. elegans neuromuscular junction in a sexually dimorphic manner. eLife10, e67170 (2021).
7. M. Padmanarayana, H. Liu, F. Michelassi, L. Li, D. Betensky, M. J. Dominguez, R. B. Sutton, Z. Hu, J. S. Dittman, A unique C2 domain at the C terminus of Munc13 promotes synaptic vesicle priming. Proc. Natl. Acad. Sci. U. S. A.118, e2016276118 (2021).
8. H. Liu*, L. Li*, S. Sheoran, Y. Yu, J. E. Richmond, J. Xia, J. Tang, J. Liu, Z. Hu, The M domain in UNC-13 regulates the probability of neurotransmitter release. Cell Rep.34, 108828 (2021).
9. H. Liu*, L. Li*, M. Krout*, S. Sheoran, Q. Zhao, J. Chen, H. Liu, J. E. Richmond, Z. Hu, Protocols for electrophysiological recordings and electron microscopy at C. elegans neuromuscular junction. STAR Protoc.2, 100749 (2021).
10. L. Li*, H. Liu*, M. Krout, J. E. Richmond, Y. Wang, J. Bai, S. Weeratunga, B. M. Collins, D. Ventimiglia, Y. Yu, J. Xia, J. Tang, J. Liu, Z. Hu, A novel dual Ca2+ sensor system regulates Ca2+-dependent neurotransmitter release. J. Cell Biol.220, e202008121 (2021).
11. G. Snieckute, O. Baltaci, H. Liu, L. Li, Z. Hu, R. Pocock, mir-234 controls neuropeptide release at the Caenorhabditis elegans neuromuscular junction. Mol. Cell. Neurosci.98, 70–81 (2019).
12. H. Liu*, L. Li*, D. Nedelcu, Q. Hall, L. Zhou, W. Wang, Y. Yu, J. M. Kaplan, Z. Hu, Heterodimerization of UNC-13/RIM regulates synaptic vesicle release probability but not priming in C. elegans. eLife8, e40585 (2019).
13. L. Li*, H. Liu*, Q. Hall, W. Wang, Y. Yu, J. M. Kaplan, Z. Hu, A Hyperactive Form of unc-13 Enhances Ca2+ Sensitivity and Synaptic Vesicle Release Probability in C. elegans. Cell Rep.28, 2979-2995.e4 (2019).
14. V. Tikiyani, L. Li, P. Sharma, H. Liu, Z. Hu, K. Babu, Wnt Secretion Is Regulated by the Tetraspan Protein HIC-1 through Its Interaction with Neurabin/NAB-1. Cell Rep.25, 1856-1871.e6 (2018).
15. P. Sharma*, L. Li*, H. Liu, V. Tikiyani, Z. Hu, K. Babu, The Claudin-like Protein HPO-30 Is Required to Maintain LAChRs at the C. elegans Neuromuscular Junction. J. Neurosci. Off. J. Soc. Neurosci.38, 7072–7087 (2018).
16. H. Liu*, L. Li*, W. Wang, J. Gong, X. Yang, Z. Hu, Spontaneous Vesicle Fusion Is Differentially Regulated at Cholinergic and GABAergic Synapses. Cell Rep.22, 2334–2345 (2018).
17. L. Li*, H. Liu*, W. Wang, M. Chandra, B. M. Collins, Z. Hu, SNT-1 Functions as the Ca2+ Sensor for Tonic and Evoked Neurotransmitter Release in Caenorhabditis Elegans. J. Neurosci. Off. J. Soc. Neurosci.38, 5313–5324 (2018).
18. X.-J. Tong, E. J. López-Soto, L. Li, H. Liu, D. Nedelcu, D. Lipscombe, Z. Hu, J. M. Kaplan, Retrograde Synaptic Inhibition Is Mediated by α-Neurexin Binding to the α2δ Subunits of N-Type Calcium Channels. Neuron95, 326-340.e5 (2017).
19. L. Li, T. Wan, M. Wan, B. Liu, R. Cheng, R. Zhang, The effect of the size of fluorescent dextran on its endocytic pathway. Cell Biol. Int.39, 531–539 (2015).
20. S. Chen*, L. Li*, J. Li*, B. Liu, X. Zhu, L. Zheng, R. Zhang, T. Xu, SEC-10 and RAB-10 coordinate basolateral recycling of clathrin-independent cargo through endosomal tubules in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U. S. A.111, 15432–15437 (2014).
* Contributed equally.
