CIMR-Lin Mei

Research Group

Lin Mei

linmei(at)cimrbj.ac.cn

Lab Website

Distinguished Investigator & Director

Synapse, Neuromuscular Junction, Myasthenia Gravis,

ALS, Psychiatric Disorders

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linmei(at)cimrbj.ac.cn

Lab Website

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B.S. in Clinical Medicine Science, Jiangxi Medical College, China

Ph. D. in Pharmacology and Toxicology, University of Arizona, USA

Work Experience

2023-Present

Distinguished Investigator & Director, Chinese Institutes for Medical Research, Beijing, China

2023-Present

Chair Professor, Capital Medical University, China

2017-2023

Chair Professor and Chair, Department of Neurosciences, Allen C. Holmes Professor, and Inaugural Director, Cleveland Brain Health Initiative (CBHI), Case Western Reserve University School of Medicine, USA

2004-2017

Chair Professor and Georgia Eminent Scholar, Institute of Molecular Medicine and Genetics (as Director, 2009-2014), Medical College of Georgia, Augusta University, and Inaugural Chair of Department of Neuroscience and Regenerative Medicine (2014-2017), USA

1999-2004

Assistant Professor and Associate professor, University of Alabama at Birmingham, USA

1994-1999

Assistant Professor, University of Virginia, USA

1989-1994

Postdoctoral Fellow, Johns Hopkins University School of Medicine, USA

Honors and Awards

2025

Consulting Editor, Journal of Clinical Investigation

2020

Associate Editor-in-Chief, Cell & Bioscience

2017

Fellow, American College of Neuropsychopharmacology (ACNP)

2013

Fellow, Association for the Advancement of Science (AAAS)

2010-2016

Associate Editor, Journal of Neuroscience

2008

Mathilde Solowey Lecture Award in Neurosciences and Georgia Research Alliance Eminent Scholar in Neuroscience

2008

Distinguished Investigator, National Alliance for Research on Schizophrenia and Depression (NARSAD)

Research Interests

The brain contains billions of nerve cells, or neurons, which receive and integrate signals from the environment and govern the body's responses. Neuronal activity is made possible by synapses, contact between neurons or between a neuron and its target cell such as a muscle fiber or gland cell. Neurotransmitter molecules are released from the presynaptic membrane and activate receptors on the postsynaptic membrane, thus establishing neuronal communication. As such, synapses are fundamental units of neural circuitry and enable complex behaviors. Research in Mei lab has focused on mechanisms of synapse formation and maintenance, and how their changes cause neurological disorders such as neuromuscular disorders and psychiatric disorders such as schizophrenia, autism, and depression. Hope that lab's research will contribute to the development of novel diagnostic and therapeutic strategies for diseases associated with synaptopathy.

Major Contributions

1. Discovered that LRP4 is a receptor of agrin that activates the transmembrane tyrosine kinase MuSK (Neuron, 2008; Genes & Dev., 2012)

2. Found anti-LRP4 and -agrin autoantibodies in patients with myasthenia gravis and showed in animal models that they are pathogenic, providing new leads for diagnosis and treatment of myasthenia gravis (Archive Neurol., 2012; PLoS One, 2014; J. Clin. Invest., 2013; Neuroscience, 2018; Neurology, 2021)

3. Revealed signaling mechanisms downstream of MuSK, including that rapsyn serves as an E3 ligase and undergoes liquid phase condensation, both events required for neuromuscular junction formation (Neuron, 2002, 2003, 2008, 2016; eLife, 2019; Neuron, 2021) , suggesting that rapsyn may act as a signaling protein, in addition to its classic scaffolding role.

4. Explored retrograde signaling pathways for muscles to regulate motoneuron differentiation (via muscle β-catenin and yet unidentified presynaptic protein that interacts with muscle LRP4 (Nature Neuroscience, 2008; Neuron, 2012; eLife, 2015)

5. Discovered that the neuregulin 1 (NRG1)-ErbB4 pathway promotes GABAergic transmission to regulate many behaviors including working memory, fear, attention and pain (Neuron, 2000, 2007; PNAS, 2010a, 2010b; Neuron, 2013, 2014, 2018, 2022)

6. Revealed pathophysiological mechanisms of neuropsychiatric disorders such as depression, schizophrenia and autism by studying risk genes including erbin, cullin 3, Caspr3, TMEM108 and NRG3 (Nature Neurosci, 2013; PNAS, 2017, 2018; Neuron, 2020; JCI, 2021; Current Biol., 2021)

Representative Publications *：Co-first author; #：Co-corresponding author

Shen C*, Zhang B*, Lu Y*, Figueiredo D‎, Wu H, Arnab B, Xiong WC and Mei L. Antibodies against low-density lipoprotein receptor-related protein 4 induce myasthenia gravis. Journal of Clinical lnvestigation, 2013, 123: 5190-5202. DOI: 10.1172/JCI66039

Sun XD*^#, Li L*, Liu F, Huang ZH, Bean JC, Jiao HF, Barik A, Kim SM, Wu H, Shen C, Tian Y, Lin TW, Bates R, Sathyamurthy A, Chen YJ, Yin DM, Xiong L, Lin HP, Hu JX, Li BM, Gao TM, Xiong WC, Mei L^#. Lrp4 in astrocytes modulates glutamatergic transmission. Nature Neuroscience, 2016, 19: 1010-1018. DOI: 10.1038/nn.4326

Li L*, Cao Y*, Wu H, Ye X, Zhu Z, Xing G, Shen C, Barik A, Zhang B, Xie X, Zhi W, Gan L, Su H, Xiong WC, Mei L. Enzymatic activity of the scaffold protein rapsyn for synapse formation. Neuron, 2016, 92: 1007-1019. DOI: 10.1016/j.neuron.2016.10.023

Tan Z, Robinson H, Yin D, Liu Y, Liu F, Wang H, Lin TW, Xing G, Xiong WC, Mei L. Dynamic ErbB4 activity in hippocampal-prefrontal synchrony and top-down attention in rodents. Neuron, 2018, 98: 380-393. DOI: 10.1016/j.neuron.2018.03.018

Dong Z*, Chen W*, Chen C, Wang H, Cui W, Tan Z, Robinson H, Gao N, Luo B, Zhang L, Zhao K, Xiong WC and Mei L. CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation. Neuron, 2020, 105: 475-490. DOI: 10.1016/j.neuron.2019.10.035 (Cover)

Chen WB*, Luo B*, Gao NN*, Li HW, Wang HS, Li L, Cui WP, Zhang L, Sun D, Liu F, Dong ZQ, Ren X, Zhang HS, Su HB, Xiong WC, and Mei L. Neddylation stabilizes Nav1.1 to maintain interneuron excitability and prevent seizures in murine epilepsy models. Journal of Clinical lnvestigation, 2021, 15: 131. DOI: 10.1172/JCI136956

Xing G, Jing H, Yu Z, Chen P, Wang H, Xiong WC, and Mei L. Membraneless condensates by Rapsn phase separation as a platform for neuromuscular junction formation. Neuron, 2021, 109: 1963-1978. DOI: 10.1016/j.neuron.2021.04.021 (Cover)

Cui W, Gao N, Dong Z, Shen C, Zhang H, Luo B, Chen P, Comoletti D, Jing H, Wang H, Robinson H, Xiong WC, and Mei L. In-trans neuregulin3-Caspr3 interaction controls DA axonal bassoon cluster development. Current Biology, 2021, 31: 3330-3342.e7. DOI: 10.1016/j.cub.2021.05.045

Wang H, Chen W, Dong Z, Xing G, Cui W, Yao L, Zou WJ, Robinson HL, Bian Y, Liu Z, Zhao K, Luo B, Gao N, Zhang H, Ren X, Yu Z, Meixiong J, Xiong WC, and Mei L. A novel spinal neuron connection for heat sensation. Neuron, 2022, 110: 2315-2333. DOI: 10.1016/j.neuron.2022.04.021

Cao R, Chen P, Wang H, Jing H, Zhang H, Xing G, Luo B, Pan J, Yu Z, Xiong WC, Mei L. Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals. Nature Communications, 2023, 14: 744. DOI: 10.1038/s41467-023-36454-8

Full List of Publications Can Be Found Here