Sang H. Lee, PhD

Professor

Locations

Pharmacology and Toxicology

Contact Information

General Interests

Neuropharmacology

Education

PhD, Biochemistry, Gyeongsang National University, South Korea, 1998

Research Interests

Synapses are fundamental functional units of neurons. Dynamic remodeling of synapses by the addition of new synapses or the elimination of existing synapses is crucial for neural circuit function and information storage. Aberrant synapse loss is directly associated with multiple neuropsychological diseases including major depressive disorder and Alzheimer’s disease. However, molecular mechanisms involved in synapse loss are yet poorly understood. The long-term goal of my research program is to understand molecular and cellular mechanisms of synaptic plasticity, especially the ones relevant to synapse weakening and loss. Our current research projects focus on recently identified two novel secreted factors that have profound effect on excitatory and GABAergic synapses, respectively. We use a multidisciplinary approach that include biochemistry, molecular biology, cell biology, a variety of imaging techniques (confocal, two-photon, super-resolution, and real time-imaging), electrophysiology, behavioral tests, and mouse genetics.

Activity-dependent Remodeling of Excitatory Synapses

We recently identified a neuronal protein, Proline-rich 7 (PRR7), as a novel Wnt inhibitor that promotes excitatory synapse loss in local neurons. Remarkably, PRR7 is secreted via extracellular vesicles called exosomes in an activity-dependent manner. Exosomes containing elevated levels of PRR7 are absorbed by neurons and promotes the loss of excitatory synapses in recipient neurons. We are investigating the molecular mechanisms by which PRR7 induces the loss of excitatory synapses. In addition, we study the potential role of PRR7 in the synapse loss associated with neurodegenerative diseases including Alzheimer’s disease.

Activity-dependent Modulation of Inhibitory Synapses

Inhibitory synaptic transmission via GABAergic synapses is critical for shaping network activity and maintaining neural circuit functionality. Defective and aberrant GABAergic synapses are associated with multiple neuropsychological conditions including mood disorders. However, molecular mechanisms involved in the regulated elimination of inhibitory synapses are poorly understood. TAFA2 is a brain-specific, novel chemokine-like protein expressed by neurons. Our recent studies using TAFA2 gene knockout animals indicate that TAFA2 is involved in anxiety and fear responses. We are investigating the mechanism and signaling pathways by which TAFA2 induces the loss of GABAergic synapses.

(Nieves Torres D, Lee SH.) Front Mol Neurosci. 2023;16:1187300 PMID: 37181650 PMCID: PMC10172472 05/14/2023
(Kearney G, Grau D, Nieves Torres D, Shin SM, Lee SH.) Sci Rep. 2022 Mar 08;12(1):4090 PMID: 35260764 PMCID: PMC8904762 SCOPUS ID: 2-s2.0-85126076405 03/10/2022
(Mammoto T, Hunyenyiwa T, Kyi P, Hendee K, Matus K, Rao S, Lee SH, Tabima DM, Chesler NC, Mammoto A.) Front Bioeng Biotechnol. 2022;10:823642 PMID: 35252132 PMCID: PMC8896883 SCOPUS ID: 2-s2.0-85125874454 03/08/2022
(Shin SM, Skaar S, Danielson E, Lee SH.) Sci Rep. 2020 Jan 09;10(1):83 PMID: 31919468 PMCID: PMC6952429 SCOPUS ID: 2-s2.0-85077694386 01/11/2020
(Lee SH, Shin SM, Zhong P, Kim HT, Kim DI, Kim JM, Heo WD, Kim DW, Yeo CY, Kim CH, Liu QS.) Nat Commun. 2018 Aug 24;9(1):3434 PMID: 30143647 PMCID: PMC6109165 SCOPUS ID: 2-s2.0-85052238097 08/26/2018
(Choi JH, Jeong YM, Kim S, Lee B, Ariyasiri K, Kim HT, Jung SH, Hwang KS, Choi TI, Park CO, Huh WK, Carl M, Rosenfeld JA, Raskin S, Ma A, Gecz J, Kim HG, Kim JS, Shin HC, Park DS, Gerlai R, Jamieson BB, Kim JS, Iremonger KJ, Lee SH, Shin HS, Kim CH.) Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E1041-E1050 PMID: 29339520 PMCID: PMC5798319 SCOPUS ID: 2-s2.0-85041206288 01/18/2018
(Kim HT, Lee MS, Jeong YM, Ro H, Kim DI, Shin YH, Kim JE, Hwang KS, Choi JH, Bahn M, Lee JJ, Lee SH, Bae YK, Lee JS, Choi JK, Kim NS, Yeo CY, Kim CH.) Sci Rep. 2017 Oct 16;7(1):13278 PMID: 29038508 PMCID: PMC5643531 SCOPUS ID: 2-s2.0-85031779920 10/19/2017
(Zhang N, Zhong P, Shin SM, Metallo J, Danielson E, Olsen CM, Liu QS, Lee SH.) J Neurosci. 2015 Feb 04;35(5):1892-904 PMID: 25653350 PMCID: PMC4315826 SCOPUS ID: 2-s2.0-84922355999 02/06/2015
(Danielson E, Lee SH.) PLoS One. 2014;9(12):e115298 PMID: 25531531 PMCID: PMC4274056 SCOPUS ID: 2-s2.0-84919798286 12/23/2014
(Shin SM, Zhang N, Hansen J, Gerges NZ, Pak DT, Sheng M, Lee SH.) Nat Neurosci. 2012 Dec;15(12):1655-66 PMID: 23143515 PMCID: PMC3804128 SCOPUS ID: 2-s2.0-84870494059 11/13/2012
(Danielson E, Zhang N, Metallo J, Kaleka K, Shin SM, Gerges N, Lee SH.) J Neurosci. 2012 May 16;32(20):6967-80 PMID: 22593065 PMCID: PMC3365591 SCOPUS ID: 2-s2.0-84861121293 05/18/2012
(Danielson E, Metallo J, Lee SH.) Channels (Austin). 2012;6(5):393-7 PMID: 22878254 PMCID: PMC3508780 SCOPUS ID: 2-s2.0-84878175337 08/11/2012

果冻影院