个人简介:
刘东鑫2009年博士毕业后留校任教,长期从事血脑屏障稳态研究,着重阐明了细菌侵袭穿过血脑屏障致新生儿细菌性脑膜炎发病的作用机制。我们发现:组成血脑屏障的脑微血管内皮细胞血管腔面表达Caspr1质膜蛋白,可以作为新生儿脑膜炎致病菌大肠杆菌分泌的侵袭蛋白IbeA的受体,通过IbeA(配体)- Caspr1(受体)的相互作用,引起宿主细胞骨架蛋白重排,帮助细菌侵袭进入脑血管内皮细胞并进一步穿过血脑屏障引起脑膜炎发生。同时鉴定出Caspr1蛋白与IbeA相互作用的最小结构域(短肽),昆虫细胞表达和纯化的短肽也能够显著阻断细菌侵袭穿过血脑屏障引起的脑膜炎发生。Caspr1作为首次鉴定的细菌性脑膜炎大肠杆菌的受体,可以为新生儿细菌性脑膜炎的防治提供新的靶标。上述研究成果发表在Nature子刊Nature Communication。2019-2022年先后在纽约医学院Dr. Chung lab和哈佛附属精神病医院McLean Hospital Dr. Kim Lab进行博士后训练,主要从事iPSC诱导分化的神经元在精神分裂中的作用机制研究,研究成果发表在Nature,Molecular Psychiatry,Nature neuroscience,Neuron等国际著名期刊。于2022年12月全职回国,并作为青年拔尖人才引进至中国医科大学生命科学学院工作,先后获得国家自然科学基金青年基金和面上资金的资助。
联系方式:dxliu@cmu.edu.cn
研究成果:
1.Dongxin Liu*, Amy Zinski, Akanksha Mishra, Haneul Noh, Gun-Hoo Park, Yiren Qin, Oshoname Olorife, James M Park, Chiderah P Abani, Joy S Park, Janice Fung, Farah Sawaqed, Joseph T Coyle, Eli Stahl, Jaroslav Bendl, John F Fullard, Panos Roussos, Xiaolei Zhang, Patric K Stanton, Changhong Yin, Weihua Huang, Hae-Young Kim, Hyejung Won, Jun-Hyeong Cho, Sangmi Chung*. Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development.Molecular Psychiatry2022,27: 4218-4233.(*共同通讯作者,中科院1区,影响因子11)
2.Weidong Zhao#,Dongxin Liu#, Jiayi Wei, Ziwei Miao, Ke Zhang, Zhengkang Su, Xuewei Zhang, Qiang Li, Wengang Fang, Xiaoxue Qin, Deshu Shang, Bo Li, Qingchang Li, Liu Cao, Kwang Sik Kim, Yuhua Chen. Caspr1 is a host receptor for meningitis-causing Escherichia coli.Nature Communications. 2018;9:2296(#共同第一作者,中科院1区,影响因子11.878)
3. Tae-Yoon Park, Jeha Jeon, Nayeon Lee, Jisun Kim 1, Bin Song, Jung-Ho Kim, Sang-Kyou Lee,Dongxin Liu, Young Cha, Minseon Kim, Pierre Leblanc, Todd M Herrington, Bob S Carter, Jeffrey S Schweitzer, Kwang-Soo Kim. Co-transplantation of autologous Treg cells in a cell therapy for Parkinson's disease.Nature.2023 Jul;619(7970):606-615 (参与作者,中科院1区,影响因子64.8)
4. Qian Zhu, Akanksha Mishra, Joy S Park,Dongxin Liu, Derek T Le, Sasha Z Gonzalez, Morgan Anderson-Crannage, James M Park, Gun-Hoo Park, Laura Tarbay, Kamron Daneshvar, Matthew Brandenburg, Christina Signoretti, Amy Zinski, Edward-James Gardner, Kelvin L Zheng, Chiderah P Abani, Carla Hu, Cameron P Beaudreault, Xiao-Lei Zhang, Patric K Stanton, Jun-Hyeong Cho, Libor Velíšek, Jana Velíšková, Saqlain Javed, Christopher S Leonard, Hae-Young Kim, Sangmi Chung. Human cortical interneurons optimized for grafting specifically integrate, abort seizures, and display prolonged efficacy without over-inhibition. Neuron. 2023;111:807-823(参与作者,中科院1区,影响因子18.688)
5. Gun-Hoo Park ,Haneul Noh, Zhicheng Shao,Peiyan Ni, Yiren Qin,Dongxin Liu, Cameron P Beaudreault, Joy S Park, Chiderah P Abani, James M Park, Derek T Le, Sasha Z Gonzalez, Youxin Guan, Bruce M Cohen, Donna L McPhie,Joseph T Coyle, Thomas A Lanz, Hualin S Xi, Changhong Yin, Weihua Huang, Hae-Young Kim,Sangmi Chung, Activated microglia cause metabolic disruptions in developmental cortical interneurons that persist in interneurons from individuals with schizophrenia. Nat Neurosci 23, 1352-1364 (2020).(参与作者,中科院1区,影响因子23.688)
6. Shuhong Zhang#,Dongxin Liu#, Li Wang, Yuhua Li, Yanhua Wang, Hu Zhang, Zhengkang Su , Wengang Fang, Xiaoxue Qin, Deshu Shang, Bo Li, Xiaoning Han, Weidong Zhao, Yuhua Chen. A CASPR1-ATP1B3 protein interaction modulates plasma membrane localization of Na+/K+-ATPase in brain microvascular endothelial cells, J Biol Chem. 2019;294:6375-6386(#共同第一作者,中科院2区,影响因子4.238)
科研项目:
1.国家自然科学基金青年项目,81201255,介导阪崎肠杆菌侵袭人脑微血管内皮细胞的cPLA2α上游信号分子的研究,2013/01-2015/12,23万元(已结题)
2.辽宁省科学技术厅支持中国医科大学高质量发展科技资金项目,2023JH2/ 20200023,通过阻断大肠杆菌IbeA与宿主Caspr1互作探讨防治脑膜炎发生的新策略,2023/12/01-2025/11/30,30万元(在研)
3.国家自然科学基金面上项目,82471750,脑膜炎大肠杆菌分泌IbeA干扰出生后海马神经元发育在神经系统后遗症中的作用机制,2025/01-2028/12,49万元(在研)