[Research Focus]

Neurological diseases, including neurodegenerative and neurodevelopmental diseases, affect the lives and health of millions of patients worldwide. However, there is still a lack of effective treatments for these diseases, in part because of our limited understanding of the pathogenic mechanisms of them. Dr. Yichang Jia laboratory in School of Basic Medical Sciences, Tsinghua University focuses on: 1) The development of rational animal and cell models for neurodegenerative diseases, especially Amyotrophic Lateral Sclerosis (ALS); 2) The molecular mechanisms underlying the disease pathogenesis and progression by using these animal models, such as disease mutation knock-in models; 3) The exploration of novel treatments for the diseases with gene therapy, such as Adeno-Associated Virus (AAV)-based gene expression and Anti-Sense Oligonucleotide (ASO)-mediated gene expression regulation.

[Education & Experience]

[Selected Publications]

• 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. DOI: 10.1038/s41467-023-43483-w. PMID: 38001106. Yichang Jia: Co-corresponding author. We develop a Multi-Animal Mesh Model Alignment (MAMMAL) system, an algorithm to enable surface motion captures of multiple freely moving animals and quantitative behavior measurement in a non-invasive manner.
• 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 Jul;33(7):497-515. doi: 10.1038/s41422-023-00798-z. PMID: 37142673. Yichang Jia: Co-corresponding author. We characterize an ER-localized chloride channel that maintains ER ion homeostasis and link its dysfunction to ALS. 
• 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. Yichang Jia: Corresponding author. We demonstrate that spliceosome pausing at detained intron is a new disease mechanism underlying neurodegeneration.
• TCF7L2 a molecular switch in midbrain controls mammal vocalization through a transcriptional repression mechanism. Huihui Qi, Li Luo, Caijing Lu, Runze Chen, Xiaohui Zhang, and Yichang Jia. Molecular Psychiatry. 2023 Apr;28(4):1703-1717. doi: 10.1038/s41380-023-01993-5. PMID: 36782064. Yichang Jia: Corresponding author. We identify TCF7L2 as a key transcriptional factor in midbrain that regulates mammal vocalization from mouse to human.
• Expression of TCF7L2 in midbrain Vglut2-positive neurons. Huihui Qi, Li Luo, Caijing Lu, Runze Chen, Xiaohui Zhang, Yichang Jia. Molecular Psychiatry. 2023 Apr;28(4):1397. doi: 10.1038/s41380-023-02116-w. PMID: 37225871. Yichang Jia: Corresponding author.
•  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. Yichang Jia: Corresponding author. Provide in vivo evidence that a less off-target approach corrects one of disease pathologies shown in a C9ORF72 repeat expansion ALS mouse model.  
• 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;143(5):1350-1367. doi: 10.1093/brain/awaa076. PMID: 32358598. Yichang Jia: Corresponding author. Provide in vivo evidence that stress granule misprocessing is pathogenic in a national FUS knockin ALS mouse model.  
• 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: 0.1038/s41598-020-59455-9. PMID: 32051525. Yichang Jia: Corresponding author. Establish ENU-induced mutagenesis screening for desired phenotypes in mouse.
• 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. Yichang Jia: First author. Identification of a mutation of a U2 snRNA gene that causes global disruption of alternative splicing and neurodegeneration by mouse forward genetics approach. Provide in vivo evidence that pre-mRNA splicing abnormalities is detrimental to neuron survival. 
• 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. Yichang Jia: First author.
• 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. Epub 2005 Mar 9. PMID: 15758952. Yichang Jia: Co-first author. We demonstrated TRPC channels contribute to the BDNF-induced elevation of Ca2+ at the growth cone and are required for BDNF-induced chemo-attractive turning.
• TRPC channels promote cerebellar granule neuron survival. Jia Y, Zhou J, Tai Y, Wang Y. Nat Neurosci. 2007 May;10(5):559-67. Epub 2007 Apr 1. PMID: 17396124. Yichang Jia: First author. We demonstrated TRPC3/6 contribute to the BDNF/TrkB-mediated neuronal survival. 
• 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. Epub 2008 May 30. PMID:18516035. Yichang Jia: author.