Faculty
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Shim, Jae-won, Ph.D.Associate Professor, Vice head of department
Human Pluripotent Stem Cells, Stem Cell Differentiation
Room 208, SIMS
+82-41-413-5014
shimj@sch.ac.kr
Laboratory of Stem cell Differentiation
Our research is focused on the derivation of functional neurons from various cell sources including human pluripotent stem (hPS) cells. One main application of our laboratory is the utilization of human ES or iPS cell-derived neurons for the development of cell replacement therapy to cure neurodegeneration disease, especially Parkinson’s disease (PD). Secondly, we also direct our research interests to utilize normal and disease-specific pluripotent stem cell lines for studying the function of genes involved in human brain development and in the pathology of neurodegeneration disease.
Midbrain Dopamine Neurons
Our previous study generated a novel floor plate-based strategy for the derivation of human dopamine (DA) neurons that efficiently engraft in vivo. Midbrain floor plate precursors are differentiated from hPSCs by exposure to small molecule activators of SHH and canonical WNT signaling. Engraftable midbrain DA neurons are obtained and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm the identity of hPSC-derived midbrain DA neurons. Excellent DA neuron survival, function, and lack of neural overgrowth in the animal models indicate promise for the development of cell-based therapies in PD.
Hindbrain Serotonin Neurons and Organoids
Serotonin neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. We established a novel strategy to generate hindbrain serotonin neurons from hPSCs, which involves the formation of ventral-type neural progenitor cells and stimulation of the hindbrain serotonin neural development. A caudalizing agent, retinoid acid (RA), is used to direct the cells into the hindbrain cell fate. hPSCs successfully develop into serotonin-expressing neurons using our protocol. Additionally, our monolayer differentiation system can be further modified to generate serotonin neuron-enriched hindbrain-like organoids. Our methodology may become a powerful tool for future studies related to serotonin neurotransmission.
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Principal Investigator Jae-won Shim Ph.D. Biography B.S. in Chemical Engineering, Seoul National University, Korea M.S. in Biological Engineering, Seoul National Universit,, Korea Ph.D. in Biological Engineering, Seoul National University, Korea Postdoctoral Fellow, Hanyang University, Korea Postdoctoral Fellow, Sloan Kettering Institute, New York, USA Assistant Professor, Soonchunhyang Institute of Medi-bio Science(SIMS), Soonchunhyang University, Korea Associate Professor, Soonchunhyang Institute of Medi-bio Science(SIMS), Soonchunhyang University, Korea Postdoctoral Researcher Lesly Puspita Ph.D. Research interest - Brain region specific neuronal differentiation from hPSC - Organoid formation from hPSC for disease modeling study - Application of genome editing system in stem cells Graduated Students Vincencius Vidyawan Research interest - Role of autophagy in neuronal development - Differentiation of hindbrain serotonin neurons from hPSC Virginia Juwono Research interest - Hindbrain R1 regional differentiation from hPSC - Role of RSPO2 gene in midbrain development Intern Students
Stephanie Widiriyadi Research interest - Screening of environmental pollutants based on brain organoid system |
Riessland M, Kolisnyk B, Kim TW, Cheng J, Ni J, Pearson JA, Park EJ, Dam K, Acehan D, Ramos-Espiritu LS, Wang W, Zhang J, Shim JW, Ciceri G, Brichta L, Studer L, Greengard P (2019) Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons. Cell Stem Cell 25(4):514-530.
Rhee YH, Puspita L, Sulistio YA, Kim SW, Vidyawan V, Elvira R, Chang MY, Shim JW*, Lee SH* (2019) Efficient Neural Differentiation of hPSCs by Extrinsic Signals Derived from Co-cultured Neural Stem or Precursor Cells. Molecular Therapy 27(7):1299-1312. *co-corresponding
Puspita L, Chung SY, Shim JW (2017) Oxidative stress and cellular pathologies in Parkinson’s disease. Molecular Brain 10:53.
Chung SY, Kishinevsky S, Mazzulli JR, Graziotto J, Mrejeru A, Mosharov EV, Puspita L, Valiulahi P, Sulzer D, Milner TA, Taldone T, Krainc D, Studer L, Shim JW (2016) Parkin and PINK1 patient iPSC-derived midbrain dopamine neurons exhibit mitochondrial dysfunction and α-synuclein accumulation. Stem Cell Reports 7(4):664-677.
Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim JW, Kriks S, Taldone T, Fusaki N, Tomishima MJ, Krainc D, Milner TA, Rossi DJ, Studer L. (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13(6):691-705.
Kriks S*, Shim JW*, Piao J, Ganat YM, Wakeman DR, Xie Z, Carrillo-Reid L, Auyeung G, Antonacci C, Buch A, Yang L, Beal MF, Surmeier DJ, Kordower JH, Tabar V, Studer L. (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease. Nature 480:547-551. *equally contributed
Shim JW, Park CH, Bae YC, Bae JY, Chung S, Chang MY, Koh HC, Lee HS, Hwang SJ, Lee KH, Lee YS, Choi CY, Lee SH. (2007) Generation of functional dopamine neurons from neural precursor cells isolated from the subventricular zone and white matter of the adult rat brain using Nurr1 overexpression. Stem Cells 25(5):1252-62.
Shim JW, Koh HC, Chang MY, Roh E, Choi CY, Oh YJ, Son H, Lee YS, Studer L, Lee SH. (2004) Enhanced in vitro midbrain dopamine neuron differentiation, dopaminergic function, neurite outgrowth, and 1-methyl-4-phenylpyridium resistance in mouse embryonic stem cells overexpressing Bcl-XL. Journal of Neuroscience 24(4):843-52.
