贾怡昌

贾怡昌 博士， 清华大学医学院研究员

电子邮件：yichangjia@mail.tsinghua.edu.cn

贾怡昌博士，清华大学医学院长聘教授，北大-清华生命科学联合中心，清华-IDG麦戈文脑科学联合研究院，清华大学脑与智能实验室研究员。主要从事神经元存活和神经退行性疾病发病机制的研究。2006年在中科院神经科学研究所获得博士学位，师从王以政院士。2007年，加入美国小鼠遗传圣地杰克逊研究所Dr. Susan Ackerman（美国科学院院士）实验室，利用小鼠遗传学研究神经退行性疾病的发病机制。2012年获得了美国健康研究院颁发的独立科学研究人奖（K99/R00, pathway to independent award），2013年入选中国国家人才计划。以第一作者和通讯作者身份在《Nature》、《Nature Neuroscience》、《Cell》、《Brain》、《Protein & Cell》、《Molecular Psychiatry》和《Cell Research》等国际知名学术期刊发表学术文章。贾怡昌教授的实验室重要关注：（1）RNA代谢异常和内质网稳态失调引起的神经退行性和神经发育障碍的疾病机制；（2）哺乳动物语音的分子机制及其在神经发育疾病中的作用；（3）建立新的神经系统疾病的细胞和动物模型。

神经功能研究是当今生命科学研究的重大问题之一，它对于我们理解脑高级认知功能，神经系统疾病发生发展，以及人工智能开发均具有重大意义。神经退行性疾病 是指大脑和脊髓神经细胞丧失的一大类疾病，全世界范围数以千万病人患病，但临床上却缺少可靠的治疗药物和方案。研究神经科学的基本问题，对于我们认识神经 行为发生及神经退行性疾病发病具有重要意义。本实验室感兴趣1）正常和病理条件下，特异的神经细胞的RNA代谢，以及RNA代谢紊乱所致神经退行性疾病的 发病机制；2）RNA结合蛋白的正常神经功能和其在神经退行性疾病致病过程中的作用；3）神经细胞内质网功能紊乱及其在神经退行性疾病中的作用。我们综合 运用神经生物学、分子细胞生物学、小鼠遗传学、高通量核酸测序和蛋白质组学等技术手段，在细胞和小鼠整体水平，研究以上问题。

 1. Three-dimensional surface motion capture of multiple freely moving pigs using MAMMAL. Liang An, Jilong Ren, Tao Yu, Tang Hai, Yichang Jia & Yebin Liu. Nature communications. 2023 Nov 25, 7727 (2023). VIEW>> 

2. Disruption of ER ion homeostasis maintained by an ER anion channel leads to ALS-like pathology. Liang Guo, Qionglei Mao, Ji He, Xiaoling Liu, Xuejiao Piao, Li Luo, Xiaoxu Hao, Bailong Xiao, Dongsheng Fan, Zhaobing Gao, and Yichang Jia. Cell Research. 2023 May 04. doi:10.1038/s41422-023-00798-z. PMID: 37142673.  VIEW>>

Highlight: Characterizing an ER-localized chloride channel that maintains ER ion homeostasis and linking its dysfunction to ALS (Co-corresponding author).   

3. A molecular brake that modulates spliceosome pausing at detained introns contributes to neurodegeneration. Dawei Meng, Qian Zheng, Xue Zhang, Li Luo, and Yichang Jia. Protein & Cell. 2023 May 08;14(5):318-336. PMID: 37027487. VIEW>>

Highlight: Demonstrating that spliceosome pausing in Bact status at detained intron, which is a new disease mechanism underlying neurodegeneration and neurodevelopmental disorders (Corresponding author).  

4. TCF7L2 acts as a molecular switch in midbrain to control mammal vocalization through its DNA binding domain but not transcription activation domain. Huihui Qi, Li Luo, Caijing Lu, Runze Chen, Xiaohui Zhang, and Yichang Jia. Molecular Psychiatry. 2023 Feb 13. doi: 10.1038/s41380-023-01993-5. PMID: 36782064. VIEW>>

Highlight: Identifying TCF7L2 as a key transcriptional factor in the midbrain that regulates mammal vocalization from mouse to human (Corresponding author).   

5. Dual-gRNA approach with limited off-target effect corrects C9ORF72 repeat expansion in vivo. Xuejiao Piao, Dawei Meng, Xue Zhang, Qiang Song, Hailong Lv, and Yichang Jia. Sci Rep. 2022 Apr 5;12(1):5672. doi: 10.1038/s41598-022-07746-8. PMID: 35383205. VIEW>>

Highlight: Providing, for the first time, in vivo evidence that a less off-target approach corrects one of the disease pathologies in a C9ORF72 repeat expansion ALS mouse model (Corresponding author).   

6. In vivo stress granule misprocessing evidenced in a FUS knock-in ALS mouse model. Zhang X, Wang F, Hu Y, Chen R, Meng D, Guo L, Lv H, Guan J, Jia Y. Brain. 2020 May 1. doi: 10.1093/brain/awaa076. PMID: 32358598. VIEW>>

Highlight: Providing in vivo evidence for the first time that stress granule misprocessing is pathogenic in a national FUS knock-in ALS mouse model (Corresponding author).   

7.  An ENU-induced mutation in Twist1 transactivation domain causes hindlimb polydactyly with complete penetrance and dominant-negatively impairs E2A-dependent transcription. Chen RZ, Cheng X, Tan Y, Chang TC, Lv H, Jia Y. Sci Rep. 2020 Feb 12;10(1):2501. doi: 10.1038/s41598-020-59455-9. PMID: 32051525. VIEW>>

Highlight: Establishing an ENU-induced mutagenesis screening at Tsinghua University for desired phenotypes in mice (Corresponding author).  

8. Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration. Jia Y, Jucius TJ, Cook SA, Ackerman SL. J Neurosci. 2015 Feb 18;35(7):3001-9. doi: 10.1523/JNEUROSCI.3678-14.2015. PMID: 25698737. VIEW>> 

9. Mutation of a U2 snRNA gene causes global disruption of alternative splicing and neurodegeneration. Jia Y, Mu JC, Ackerman SL. Cell. 2012 Jan 20;148(1-2):296-308. doi: 10.1016/j.cell.2011.11.057. PMID: 22265417. VIEW>>

Highlight: Identifying a mutation of a U2 snRNA gene that causes global disruption of alternative splicing and neurodegeneration by mouse forward genetics approach.   

10. TRPC channels promote cerebellar granule neuron survival. Jia Y, Zhou J, Tai Y, Wang Y. Nat Neurosci. 2007 May;10(5):559-67. PMID: 17396124. VIEW>>

Highlight: Demonstrating that TRPC3/6 contributes to BDNF/TrkB-mediated neuronal survival. 

11. Critical role of TRPC6 channels in the formation of excitatory synapses. Zhou J, Du W, Zhou K, Tai Y, Yao H, Jia Y, Ding Y, Wang Y. Nat Neurosci. 2008 Jul;11(7):741-3. doi: 10.1038/nn.2127. PMID:18516035. VIEW>> 

12. Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. Li Y, Jia YC, Cui K, Li N, Zheng ZY, Wang YZ, Yuan XB. Nature. 2005 Apr 14;434(7035):894-8. PMID: 15758952. VIEW>>

Highlight: Demonstrating that TRPC channels contribute to BDNF-induced elevation of Ca2+ at the growth cone and are required for BDNF-induced chemo-attractive turning (Co-first author).