Research

Through many years of research on embryonic and adult neural stem cells (NSC), mesenchymal stem cells (MSC), and pathological conditions including Rett Syndrome, a neural developmental disorder, also an autism spectrum disorder (ASD), neurodegenerative disorders including ALS, PD, and AD, as well as traumatic CNS injury such as spinal cord injury (SCI), we realized that neural inflammation plays a pivotal role in pathogenesis of all of the aforementioned pathological conditions. We postulate that the fundamental underlying logic for Neural Repair could be through establishment of non-inflammatory and neural trophic CNS microenvironment via small/macro molecules, biomaterials, exosomes, or stem cells, and etc., to enable residual neurons to exert plasticity to compensate functions of damaged neural circuits, or to allow NSC, endogenous or exogenous, to produce new neurons, forming nascent relay network to integrate into broken circuits to resume neural function via neural plasticity. To make neural repair feasible, we initiated large-scale single cell RNA-sequencing to capture the “souls/features” of each cell including NSC/MSC or cell types to establish a “Tool Cell Atlas/Dictionary”. Subsequently, through our “Cell Convertor” program, we aim to achieve reprogramming of available human autologous cells into desired therapeutic cells to improve the microenvironment for CNS repair or to replace damaged neurons. Lastly, we take system biology-based approaches to study cross interactions amongst “gut-circulation immunity-CNS immunity-Neuronal function”. We initiated single cell transcriptome-based immune typing of individuals with different age, gender, and pathological conditions, aiming at targeting CNS diseases via the periphery, including reprograming monocytes into therapeutic cells.

Biography

2022-present, Principal Investigator, The Brain Cognition and Brain Disease Institute of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

2022-present, Chair Professor, School of Life and Health Sciences at the University of Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

2009-2022, Chair, Department of Stem Cell and Regenerative Medicine, School of Medicine at Tongji University

2012-2020, Professor (with tenure), Department of Psychiatry and Biobehavioral Sciences/Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA

2007-2012, Associate Professor (with tenure), Department of Psychiatry and Biobehavioral Sciences/Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA

2001-2007, Assistant Professor (tenure track), Department of Psychiatry and Biobehavioral Sciences/Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA

1996-2001, Postdoctoral Fellow, Department of Neurobiology, Harvard Medical School

1990-1996, Ph.D. Department of Neuroscience, School of Medicine at Case Western Reserve University

1983-1987, B.S. Biochemistry, Fudan University

Selected publications

1. Zhang Y^#, Li S, Jin P, Shang T, Sun R, Lu L, Guo K, Liu J, Tong Y, Wang J, Liu S, Wang C, Kang Y, Zhu W, Wang Q, Zhang X, Yin F, Sun Y E*, and Cui L*. Dual functions of microRNA-17 in maintaining cartilage homeostasis and protection against osteoarthritis[J]. Nature Communications, 2022, 13(1): 2447.
2. Li C^#, Wu Z^#, Zhou L^#, Shao J, Hu X, Xu W, Ren Y, Zhu X, Ge W, Zhang K, Liu J, Huang R, Yu J, Luo D, Yang X, Zhu W, Zhu R, Zheng C, Sun Y E*, and Cheng L*. Temporal and spatial cellular and molecular pathological alterations with single-cell resolution in the adult spinal cord after injury[J]. Signal Transduction and Targeted Therapy, 2022, 7(1): 65.
3. Liu J^#, Wang J^#, Xu J^#, Xia H^#, Wang Y^#, Zhang C, Chen W, Zhang H, Liu Q, Zhu R, Shi Y, Shen Z, Xing Z, Gao W, Zhou L, Shao J, Shi J, Yang X, Deng Y, Wu L, Lin Q, Zheng C, Zhu W, Wang C*, Sun Y E*, and Liu Z*. Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines[J]. Cell Discovery, 2021, 7(1): 99.
4. Chen Y^#*, Yu J^#, Niu Y^#, Qin D^#, Liu H^#, Li G, Hu Y, Wang J, Lu Y, Kang Y, Jiang Y, Wu K, Li S, Wei J, He J, Wang J, Liu X, Luo Y, Si C, Bai R, Zhang K, Liu J, Huang S, Chen Z, Wang S, Chen X, Bao X, Zhang Q, Li F, Geng R, Liang A, Shen D, Jiang T, Hu X, Ma Y, Ji W*, and Sun Y E*. Modeling Rett syndrome using TALEN-edited MECP2 mutant cynomolgus monkeys[J]. Cell, 2017, 169(5): 945-955
5. Luo Y^#, Coskun V^#, Liang A^#, Yu J^#, Cheng L^#, Ge W, Shi Z, Zhang K, Li C, Cui Y, Lin H, Luo D, Wang J, Lin C, Dai Z, Zhu H, Zhang J, Liu J, Liu H, Vellis J D, Horvath S, Sun Y E*, and Li S*. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells[J]. Cell, 2015, 161(5): 1175-1186.
6. Wu H^#*, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K, Li E, Zhang Y, and Sun Y E*. Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes[J]. Science, 2010, 329(5990): 444-448.
7. Liu H^#, Chen Y, Niu Y, Zhang K, Kang Y, Ge W, Liu X, Zhao E, Wang C, Lin S, Jing B, Si C, Lin Q, Chen X, Lin H, Pu X, Wang Y, Qin B, Wang F, Wang H, Si W, Zhou J, Tan T, Li T, Ji S, Xue Z, Luo Y, Cheng L, Zhou Q, Li S, Sun Y E*, and Ji W*. TALEN-mediated gene mutagenesis in rhesus and cynomolgus monkeys[J]. Cell Stem Sell, 2014, 14(3): 323-328.
8. Coskun V^#, Wu H, Blanchi B, Tsao S, Kim K, Zhao J, Biancotti J C, Hutnick L, Krueger Jr R C, Fan G, Vellis J D, and Sun Y E*. CD133+ neural stem cells in the ependyma of mammalian postnatal forebrain[J]. PNAS, 2008, 105(3): 1026-1031.
9. He F^#, Ge W, Martinowich K, Becker-Catania S, Coskun V, Zhu W, Wu H, Castro D, Guillemot F, Fan G, Vellis J D, and Sun Y E*. A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis[J]. Nature Neuroscience, 2005, 8(5): 616-625.
10. Martinowich K^#, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G*, and Sun Y E*. DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation[J].Science, 2003, 302(5646): 890-893.
11. Sun Y E^#, Nadal-Vicens M, Misono S, Lin M Z, Zubiaga A, Hua X, Fan G, and Greenberg M E*. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms[J]. Cell, 2001, 104(3): 365-376.