PI, IDG/McGovern Institute, Tsinghua University
Office: D204, Medical Sciences Building
One of the major questions for neuroscience field is to understand the disease mechanisms underlying neurological and neurodegenerative disorders. Those diseases afflict millions of people worldwide, but so far almost no effective cure has been developed for these devastating disorders, partially due to our poor understanding of disease mechanisms. To tackle the disease mechanisms often relates to another key question in the field, the mechanisms underlying learning and memory, because impairment of learning and memory is often seen in many these diseases, including autism, schizophrenia, and Alzheimer’s disease. Since mouse shares over 90% gene similarity with human, to study chemical-induced mutant mice carrying learning and memory deficits or/and neurodegenerative phenotypes will great enhance our knowledge on the disease mechanisms and accelerate the speed in identification of novel therapeutic interventions. In addition, our disease-orientated research on these mutant genes also significantly deepens our understanding on these gene physiological functions. Our long-term goal is to combine molecular biology and mouse genetics to better understand the neurological and neurodegenerative disease mechanisms and bridge our basic research with therapeutic target discoveries. Current our research focuses include:
(1) The disease mechanisms underlying neurodegenerative disorders caused by RNA metabolism abnormalities.
Recently, increasing evidence, including ours, suggested that dysfunction of RNA metabolism may play a key role in etiology of a range of neurodegenerative disorders, especially motor neuron disease. However, the basis of RNA metabolism in specific neuron types and their subcellular compartments during both physiological and pathological conditions is largely unknown. Currently, we focus on three RNA-binding proteins, IGHMBP2, TDP43, and FUS, and study how dysfunction of these genes results in motor neuron degeneration. In addition, we are interested to learn RNA species and their metabolism in specific cell type in the brain, including motor neurons, in different experimental paradigm and pathological conditions. To gain our understanding on these aspects, we combine neurobiology, molecular and cell biology, RNA biochemistry, high through-put sequencing, and mouse forward genetics.
(2) ER homeostasis regulation and ER-stress mediated neurodegeneration.
We are also very interested in the disease mechanisms underlying neurodegeneration caused by dysfunction of cellular organelles, especially endoplasmic reticulum (ER). ER has its essential roles in protein folding and in response to misfolded protein accumulation. Disruption of ER functions has been implicated in the etiology of many human diseases, including neurodegenerative diseases. Mouse forward genetics alone with other approaches described above are employed to identify key molecules in regulation of ER homeostasis at the entire animal level.
(3) Generation of new cell and animal models for neurodegenerative and neurological diseases.
We currently adopt CRISPR/CAS9 technique to do genome manipulation in human embryonic stem cells (hESCs) and entire animals. The hESCs carrying mutations found in neurological or neurodegenerative diseases are differentiated into different neuron types we are interested in. These cells serve as in vitro models for the diseases. Meanwhile, the mutations have been also introduced into animals, majorly mouse, to generate mammalian disease models. The combination of these approaches generating cell and animal models for human diseases will provide medium to transform our basic research into promising therapeutic interventions.
[Education & Experience]
- Jiaofeng Chen, Xue Zhang, Jie Li, Chenmeng Song, Yichang Jia*, WeiXiong, Identification of a Novel ENU-Induced Mutation in Mouse Tbx1 Linked to Human DiGeorge Syndrome, Neural Plasticity Volume, 2016, 1(5836143).
- Jia, Yichang*, Jucius Thomas J, Cook Susan A, Ackerman Susan L , Loss of Clcc1 Results in ER Stress, Misfolded Protein Accumulation, and Neurodegeneration. Journal of Neuroscience, 2015.2.18, 35(7): 3001~3009.
- Yichang Jia*, John Mu, Susan Ackerman. Mutation of a U2 snRNA Gene Causes Global Disruption of Alternative Splicing and Neurodegeneration.Cell. (2012)148, 296-308.
- Jian Zhou, Wanlu Du, Kechun Zhou, Yilin Tai, Hanlan Yao, Yichang Jia, Yuqiang Ding, Yizheng Wang. Critical role of TRPC6 channels in the formation of excitatory synapses. Nature Neuroscience.(2008) 11, 741-3.
- YiqunYao, Xia Ding, Yichang Jia, Chuanxin Huang, Yizheng Wang, and Yunhui Xu. Anti-tumor effect of b-elemene in glioblastoma cells 3 depends on p38 MAPK activation. Cancer Lett. (2008)264, 127-134.
- Zenghua Wang, Bin Shen, Haolan Yao, Yichang Jia, Jing Ren, Youji Feng and Yizheng Wang. Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer. Oncogene. (2007)26, 5107-5114.
- Chuanxin Huang, Yichang Jia, Shenglian Yang, Biao Chen, Hongwei Sun, Feng Shen and Yizheng Wang. Characterization of ZNF23, a KRAB-containing protein that is downregulated in human cancers and inhibits cell cycle progression. Exp. Cell Res. (2007)313, 254-263.
- Yichang Jia*, Jian Zhou*, Yilin Tai and Yizheng Wang. TRPC channels promote cerebellar granule neuron survival. Nature Neuroscience. (2007)10, 559-567.
- Yan Li*, Yichang Jia*, Kai Cui*, Ning Li, Zai-Yu Zheng, Yi-Zheng Wang and Xiao-Bing Yuan.Essential role of TRPC channels in the guidance of nerve growth cones by brain-derived neurotrophic factor. (2005) Nature. 434, 894-898.