McLean Hospital 115 Mill Street Belmont, MA 02478
Sangmi Chung, PhD, received her BSc in microbiology from Seoul National University. She then moved to Cornell University Graduate School of Medical Sciences to pursue a graduate career in neuroscience where she earned her PhD.
Dr. Chung joined McLean Hospital in 1999 as a post-doctoral fellow in the Molecular Neurobiology Laboratory. After many years as associate neurobiologist in the Molecular Neurobiology Laboratory, she is now director of the Translational Stem Cell Neurobiology Laboratory.
With the aim of developing novel treatments, Dr. Chung’s Translational Stem Cell Neurobiology Laboratory, founded in 2015, studies brain disorders—such as schizophrenia, epilepsy, and autism—in which inhibitory interneurons—a type of neuron that functions to inhibit other neurons—are abnormal.
To find a better way to treat schizophrenia, Dr. Chung seeks to understand what goes wrong in diseased neurons. Using inhibitory interneurons from stem cells that are made from schizophrenia patients’ skin cells, she is studying these patient neurons to find out the cause of the 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 a pressing need for the development of new and more effective treatments. Dr. Chung and her staff have shown that transplantation of stem cell-derived interneurons effectively reduces seizures and other brain abnormalities. They are further developing this novel treatment using animal models of epilepsy.
Pluripotent stem cell differentiation well recapitulates normal development and thus provides a powerful tool to study the pathogenetic mechanism of developmental brain disorders. Additionally, it provides cell sources to treat the brain disorders locally and restoratively without side effects caused by systemic drug treatment. Previously, Dr. Chung has developed an efficient method for generating homogeneous populations of cortical interneurons from human pluripotent stem cells by temporal and combinatorial regulation of developmentally relevant signaling pathways. Using this platform, the lab is studying the pathogenetic mechanism of interneuron-associated brain disorders as well as developing cell therapy to restore disrupted excitation/inhibition balance caused by interneuron dysfunction.
In a study of the development of cell replacement therapy to treat brain disorders caused by interneuron dysfunction, the lab has shown that human pluripotent stem cell-derived interneurons migrate extensively, even in adult brains, integrating into the host circuitry and regulating host inhibitory balance which results in amelioration of behavioral abnormalities in animal models of epilepsy. This novel therapeutic strategy will have broader implications for other brain disorders with interneuron dysfunction, such as schizophrenia and autism. Dr. Chung and her group are developing human interneuron transplantation therapy as well as identifying the mechanistic basis of its functional efficacy.
Dr. Chung is currently examining the pathogenetic mechanism of schizophrenia in patient-derived inhibitory interneurons. Although schizophrenia emerges in late adolescence, disease progression begins early in life, before the onset of overt symptoms. To study abnormalities in the schizophrenic brain during early development, the lab will generate patient interneurons using induced pluripotent stem cell technology and will study their developmental abnormality and their interaction with the environment.
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.
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.
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.
Belmont campus - North Belknap, Room G24A