Department of Cell Biology & Anatomy
Basic Sciences Building, Room 221
Valhalla, NY 10595
The Translational Stem Cell Neurobiology Laboratory studies brain disorders in which inhibitory interneuron function is compromised, such as schizophrenia, epilepsy and autism, with the aim of developing novel therapeutics for these debilitating disorders.
Inhibitory interneurons are abnormal in schizophrenic brains. To find a better way to treat schizophrenia, we need to understand what goes wrong in diseased neurons. Now we can make schizophrenia inhibitory interneurons from stem cells that are made from patient skin cells. We are studying these patient neurons to find out what is causing their abnormalities. This study could lead to novel and more effective therapies for schizophrenia.
One in 25 people experience a seizure at some point in their life and 30% of them have seizures that cannot be treated with anti-seizure medication, presenting desperate need for the development of novel and more effective treatments. We have shown that transplantation of stem cell-derived human interneurons effectively reduce seizures and other brain abnormalities in animal models of epilepsy. We are further developing this novel therapeutics for the purpose of clinical translation.
Post Graduate Studies: McLean Hospital/Harvard Medical School
Graduate Degree: Ph.D. in Neuroscience
Graduate Degree Institution: Weill Cornell Graduate School of Medical Sciences
Undergraduate Institution: Seoul National University
Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development. Liu D, Zinski A, Mishra A, Noh H, Park GH, Qin Y, Olorife O, Park JM, Abani CP, Park JS, Fung J, Sawaqed F, Coyle JT, Stahl E, Bendl J, Fullard JF, Roussos P, Zhang X, Stanton PK, Yin C, Huang W, Kim HY, Won H, Cho JH, Chung S. Mol Psychiatry. 2022 Jun 14. doi: 10.1038/s41380-022-01654-z. Online ahead of print. PMID: 35701597
Park, G., Noh, H., Shao, Z. et al. Activated microglia cause metabolic disruptions in developmental cortical interneurons that persist in interneurons from individuals with schizophrenia. Nat Neurosci 23, 1352–1364 (2020). https://doi.org/10.1038/s41593-020-00724-1
Shao Z, Noh H, Bin Kim W, Ni P, Nguyen C, Cote SE, Noyes E, Zhao J, Parsons T, Park JM, Zheng K, Park JJ, Coyle JT, Weinberger DR, Straub RE, Berman KF, Apud J, Ongur D, Cohen BM, McPhie DL, Rapoport JL, Perlis RH, Lanz TA, Xi HS, Yin C, Huang W, Hirayama T, Fukuda E, Yagi T, Ghosh S, Eggan KC, Kim HY, Eisenberg LM, Moghadam AA, Stanton PK, Cho JH, Chung S*. Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell-derived cortical interneurons from subjects with schizophrenia. Nature neuroscience. 2019; 22(2):229-242. PMCID: PMC6373728
Ni P, Noh H, Park GH, Shao Z, Guan Y, Park JM, Yu S, Park JS, Coyle JT, Weinberger DR, Straub RE, Cohen BM, McPhie DL, Yin C, Huang W, Kim HY, Chung S*. iPSC-derived homogeneous populations of developing schizophrenia cortical interneurons have compromised mitochondrial function. Molecular psychiatry. 2019; doi: 10.1038/s41380-019-0423-3. [Epub ahead of print]
Ni P, Noh H, Shao Z, Zhu Q, Guan Y, Park JJ, Arif F, Park JM, Abani C, Beaudreault C, Park JS, Berry E, Moghadam A, Stanton P, Hutchinson JN, Andrews B, Faux C, Parnevelas J, Eisenberg LM, Park K, Bolshakov VY and Chung S*. Large-Scale Generation and Characterization of Homogeneous Populations of Migratory Cortical Interneurons from Human Pluripotent Stem Cells. Molecular Therapy - Methods & Clinical Development 2019; 13: 414-430.
Leung A, Ahn S, Savvidis G, Kim Y, Iskandar D, Luna M, Kim K-S, Cunningham M, Chung S. Optimization of pilocarpine-mediated seizure induction in immunodeficient Nod-Scid mice. Epilepsy Research. 2015;109:114-118.
Cunningham,M, Cho J-H, Leung A, Savvidis G. Ahn S, Moon M, Lee K-J, Han J, Azimi N, Kim K-S, Bolshakov V, Chung S. Human PSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell. 2014;15:559-573.
Kim T-G, Yao R, Cho J-H, Vasudevan A, Koh A, Moon M, Datta D, Bolshakov V, Kim K-S, Chung S. Efficient specification of interneurons from human Pluripotent stem cells by dorsoventral and rostrocaudal modulation. Stem Cells. 2014;32(7):1789-180.
Chung, S., Moon, J., Leung, A. Aldrich, D., Lukianov, S., Kitayama, Y., Park, S., Li, Y., Bolshakov, V., Lamonerie, T. and Kim, K.-S. Embryonic stem cell-derived renewable and functional midbrain dopaminergic progenitors. PNAS. 2011. 108:9703.
Chung, S., Leung, A., Han, B., Chang, M., Moon, J., Kim, C., Hong, S., Pruszak, J., Isacson, O. and Kim, K.-S. Wnt1-lmx1a forms a novel autoregulatory loop and controls midbrain dopaminergic differentiation synergistically with the SHH-FoxA2 pathway. Cell Stem Cell. 2009. 5:646-58.
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 Signoretti1, 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 Velišek, Jana Veliškova, Saqlain Javed, Christopher S. Leonard and Sangmi Chung*. Human cortical interneurons optimized for grafting specifically integrate, abort seizures and display prolonged efficacy without over-inhibition. Neuron 2023; in press. DOI: https://doi.org/10/1016/j.neuron.2022.12.014 (*Senior and corresponsing author for this paper)
Search PubMed for all available publications of Sangmi Chung, Ph.D.