General

​Yuejun Chen

male

Principal Investigator, 

Laboratory of Neural Differentiation and Regeneration

Institute of Neuroscience,

Shanghai Chinese Academy of Sciences. China

Email:yuejunchen@ion.ac.cn 

Research Areas

Current Interests
1. The mechanisms of cell therapy in the adult brain
For cell therapy to succeed in neurological disorders, the grafted neuronal progenitor cells should survive and differentiate into specific types of neurons, which then send out axons and navigated in the mature CNS environment to find their target brain region. Finally, these neurons should make functional synaptic connections with their designated neurons and receive proper innervations, thus functionally replacing the lost or degenerated host neurons. The specific neuronal projection and connections in the adult brain are formed during development by complex mechanisms including multiple chemotropic guidance cues, extracellular matrix-cell interaction, cell-cell interaction, guidance of radial glial cells. However, most of these axonal guidance mechanisms diminished in the adult brain, and only a portion of guidance cues could be detected in a few defined regions at reduced level. The specificity and mechanisms of neuronal connection of grafted cells in adult host brain are largely unknown. Through the use of a synthesis of directed differentiation of stem cells, CRISPR/Cas9-mediated genome editing, cell transplantation, histology analysis, virus mediated retrograde and anterograde transsynaptic tracing and functional magnetic resonance image (fMRI), we attempt to understand the fundamental principles of axonal projection and neuronal connection of grafted neurons in the adult brain.

2. Developing novel strategies for cell therapy in PD
In PD cell therapy, the differentiation efficiency of human midbrain dopamine (mDA) neuron in the animal brain is generally low (rang from 5% to 60%). The resulting grafted cells are often mixed population of neuronal cells including mDA neurons, GABA neurons, serotonin neurons, astrocytes and other uncharacterized cells. At least two subtypes of mDA neurons, substantianigra compact (SNc) DA neurons and ventral tegmental area (VTA) DA neurons, are present in the human grafts. It has been reported that serotonin neurons in the human graft derived from human fetal mesencephalic tissues will cause graft-induced dyskinesia (GID), the most severe side effect in PD cell therapy. It is also still debated whether VTA-DA neurons in the graft contribute to the motor functional recovery of PD model animals or cause side effects as VTA neurons can widely regulate the natural reward circuitry of the brain. In most studies, the therapeutic effect of cell therapy is evaluated from xenograft of human cells in PD animals with normal brain environment. It is unknown whether similar therapeutic effects could be obtained in aged and/or diseased brain environment under homograft condition. By using CRISPR/Cas9-meditaed genome editing, multiple factors-confined reporter system, virus expression system, eletrophysiology, and directed neural differentiation, we attempt to develop novel mDA subtype specific differentiation method and determine the therapeutic effect of grafted cells in rodent brain under xenograft condition and aged non-human primate brain under homograft condition. We are also interested in developing novel PD non-human primate model to mimic the diseased host brain environment for cell therapy.

The long-term goal of our group is to develop safe and effective strategies for clinical application of cell therapy in neurodegenerative disorders.

Education

1998-2003: Bachelor. Medicine, Shanghai Medical College, 

          Fudan University, Shanghai, China.

2003-2008: Ph.D. Pharmacology, Shanghai Medical College, 

          Fudan University, Shanghai, China.

    Advisor: Dr. Lan Ma


Experience

   
Work Experience

2008.09 - 2012.12 Lecturer, Pharmacology Research Center, 

Shanghai Medical College, Fudan University. China

2012.12 - 2013.02 Associate Professor, Pharmacology Research Center,

Shanghai Medical College, Fudan University. China

2013.02 - 2015.02 Postdoctoral Fellow, Waisman Center,

University of Wisconsin-Madison. USA

Advisor: Dr. Su-Chun Zhang

2015.02 - 2016.08 Assistant Scientist, Waisman Center,

University of Wisconsin-Madison. USA

Advisor: Dr. Su-Chun Zhang

2016.08 - Present           Principal Investigator, 

       Laboratory of Neural Differentiation and Regeneration

       Institute of Neuroscience,

       Shanghai Chinese Academy of Sciences. China


Teaching Experience
   

Publications

   
Papers

(1First Author; *Corresponding author)

1. Yuejun Chen1*, Man Xiong1, Yi Dong1, Alexander Haberman,Jingyuan Cao, Huisheng Liu, and Su-Chun Zhang*. Chemical Control of Grafted Human PSC-Derived Neurons in a Mouse Model of Parkinson’s Disease. Cell Stem Cell. 2016, 18: 817-826. (6)

2. Yuejun Chen1, and Man Xiong. 2016. Reprogrammed Progenitors. Cell Stem Cell. 2016, 18:693. (Invited Preview)

3. Yuejun Chen1*, Jingyuan Cao1, Man Xiong1, Andrew J. Petersen, Yi Dong, Yunlong Tao, Cindy Tzu-Ling Huang, Zhongwei Du, and Su-Chun Zhang*. Engineering Human Stem Cell Lines with Inducible Gene Knockout using CRISPR/Cas9. Cell Stem Cell. 2015, 17: 233-244. (23)

4. Yuejun Chen1, Man Xiong, and Su-Chun Zhang*. Illuminating Parkinson's therapy with optogenetics. Nature Biotechnology. 2015, 33: 149-150. (Invited Preview) (3)

5. Hui Long, Xinru Zhu, Ping Yang, Qinqin Gao, Yuejun Chen*, and Ma L*. Myo9b and RICS modulate dendritic morphology of cortical neurons. Cerebral Cortex. 2013, 23: 71-79. (12)

6. Yuejun Chen1, Feifei Wang1, Hui Long1, Yin chen1, Ziyan Wu, and Lan Ma*. GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis. J Cell Biol. 2011, 194: 905-920. (18)

7. Yuejun Chen1, Hui Long, Ziyan Wu, Xi Jiang, and Lan Ma*. EGF transregulates opioid receptors through EGFR-mediated GRK2 phosphorylation and activation. Mol Biol Cell. 2008, 19: 2973-83. (31)

8. Ziyan Wu, Yuejun Chen*, Tong Yang, Qinqin Gao, Man Yuan, and Lan Ma. Targeted ubiquitination and degradation of G-protein-coupled receptor kinase 5 by the DDB1-CUL4 ubiquitin ligase complex. PLoS One. 2012, 7, e43997. (8)

9. Yuejun Chen1, Yan Jiang1, Wen Yue1, Yuqing Zhou, Lin Lu, and Lan Ma*. Chronic, but not acute morphine treatment, up-regulates alpha-Ca2+/calmodulin dependent protein kinase II gene expression in rat brain. Neurochem Res. 2008, 33, 2092-2098. (18)

Patents
   

Research Interests

   

Conferences

1. Invited oral presentation, Annual Meeting of Institute of Neuroscience, Chinese Academy of Science, Shanghai, China. 2010.

2. Invited oral presentation, "HOT TOPICS" IN STEM CELL BIOLOGY Satellite Synposium at the 2014 Annual Meeting of the Society For Neurosciences, Washington, USA. 2014.

3. Invited oral presentation, "HOT TOPICS" IN STEM CELL BIOLOGY Satellite Synposium at the 2015 Annual Meeting of the Society For Neurosciences, Chicago, USA. 2015.

4. Invited oral presentation, Campus Stem Cell Lab meetings, University of Wisconsin-Madison, Madison, USA. 2015


Collaboration

   

Students

Students:

Wei Yan       Graduate student  071006-Neurobiology

Peibo Xu      Graduate student  071006-Neurobiology

Hui He         Graduate student  071006-Neurobiology

Honors & Distinctions