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Seunghyi Kook, PhD

Post-Doctoral Fellow, Pharmacology


EDUCATION

August 2000 – Doctor of Science: Gwangju Institute of Science and Technology, Korea

Department of Life Science

Thesis Topic: “Caspase-mediated cleavage of focal adhesion proteins, p130cas, in apoptotic Rat-1 cells”

February 1997 – Master of Science: Gwangju Institute of Science and Technology, Korea

Department of Life Science

Thesis Topic: “Nocodazole induced apoptosis in Rat-2 Cells”

February 1995 – Bachelor of Science: Chonnam National University, Korea

Department of Microbiology

 

WORK EXPERIENCE

Postdoctoral Research Fellow                                                             May, 16 2004 to present

– Department of Pharmacology, Vanderbilt University School of Medicine

Postdoctoral Research Associate                                                     July 2001 to May 15, 2004

– Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics,

Vanderbilt University School of Medicine

– Identify PKC interaction sites on phopholipase D1.

Postdoctoral Research Fellow                                                    September 2000 to June 2001

– Department of Life Science, Gwangju Institute of Science and Technology

– Investigate caspase-dependent cleavage of tensin and the effect of tensin cleavage on actin

cytoskeleton in apoptotic cells.

 

HONORS AND FELLOWSHIPS

SCHOLARSHIPS

Best GPA Record Scholarship                                                                                        1991-1994

Chonnam National University, Korea

 

National Scholarship for Master and Ph.D degree                                                       1995-2000      Sponsored by Korea Government

 

AWARDS

KSCB young scientist Award                                                                                                   1998

The 6th Korean Society for Cell Biology (KSCB) Conference

Best Poster Award                                                                                                                   1998

The 10th Annual Meeting of the Korean Society for Molecular Biology

ASBMB 2010 Travel Award                                                                                                    2010

The American Society for Biochemistry and Molecular Biology

 

FELLOWSHIP

Overseas Post doctoral Research Fellowship                                 August 2001 to August 2002 Korea Science and Engineering Foundation (KOSEF)

Research Description

Seunghyi was a post-doc in the lab until 2014. She worked on several projects, all of which are collaborative with the lab of Eugenia Gurevich. Seunghyi focused on the role of arrestins in the activation of JNK family kinases, that often stop cell proliferation and induce cell death, as well as on direct functions of non-visual arrestins in apoptotic cell death. She recently discovered that caspase-cleaved arrestin-2 translocates to mitochondria and facilitates cytochrome C release induced by another product of caspase activity, tBid, but not other Bcl family members. This was the first demonstration that arrestins play direct role in the core of cell death machinery.

In collaboration with Eugenia we have recently discovered that arrestins bind ubiquitin ligase parkin, mutations in which are implicated in familial Parkinson’s disease. We discovered that parkin binding promotes arrestin interaction with another E3 ubiquitin ligase, Mdm2. Seunghyi is elucidating the mechanism of arrestin interactions with these two ubiquitin ligases and its role in the regulation of parkin activity in cells.

 

Seunghyi published fifteen papers and chapters from the lab:

Samaranayake, S., Vishnivetskiy, S.A., Shores, C.R., Thibeault, K.C., Kook, S.,Chen, J., Burns, M.E., Gurevich, E.V., Gurevich, V.V. Biological role of arrestin-1 oligomerization. J Neurosci, in press (2020).

Kook, S., Zhan, X., Thibeault, K., Ahmed, M.R., Gurevich, V.V., Gurevich, E.V. Mdm2 enhances ligase activity of parkin and facilitates mitophagy. Sci Rep 10 (1) 5028; doi: 10.1038/s41598-020-61796-4 (2020).

Kook, S., Vishnivetskiy, S.A., Gurevich, V.V., Gurevich, E.V. Cleavage of arrestin-3 by caspases attenuates cell death by precluding arrestin-dependent JNK activation. Cell Signal, in press (2019).

Cleghorn, W.M., Bulus, N., Kook, S., Gurevich, V.V., Zent, R., Gurevich, E. V. Non-visual arrestins regulate the focal adhesion formation via small GTPases RhoA and Rac1 independently of GPCRs. Cell Signal 42, 259-269 (2018).

Cleghorn, W.M., Branch, K.M., Kook, S., Arnette, C., Bulus, N., Zent, R., Kaverina, I., Gurevich, E.V., Weaver, A.M. Gurevich, V.V. Arrestins regulate cell spreading and motility via focal adhesion dynamics. Mol Biol Cell, 26 (4), 622-635 (2015).

Zhan, X., Kook, S., Kaoud, T.S., Dalby, K.N., Gurevich, E.V., and Gurevich, V.V. 2015. Arrestin-3-Dependent Activation of c-Jun N-Terminal Kinases (JNKs). Curr Protoc Pharmacol 68:2.12.1-2.12.26. doi: 10.1002/0471141755.ph0212s68 (2015).

Ahmed MR, Bychkov E, Kook S, Zurkovsky L, Dalby KN, Gurevich EV. Overexpression of GRK6 rescues L-DOPA-induced signaling abnormalities in the dopamine-depleted striatum of hemiparkinsonian rats. Exp Neurol 2015 Apr;266:42-54

Kook S, Gurevich VV, Gurevich EV. Arrestins in apoptosis. Handb Exp Pharmacol. 2014;219:309-339.

Zhan X, Kook S, Gurevich EV, Gurevich VV. Arrestin-Dependent Activation of JNK Family Kinases. Handb Exp Pharmacol 2014; 219, 259-280.

Kook S, Zhan X, Kaoud TS, Dalby KN, Gurevich VV, Gurevich EV. Arrestin-3 binds JNK1 and JNK2 and facilitates the activation of these ubiquitous JNK isoforms in cells via scaffolding. J Biol Chem 2013, 288 (52), 37332-42.

Kook S, Zhan X, Cleghorn WM, Benovic JL, Gurevich VV, Gurevich EV. Caspase-cleaved arrestin-2 and BID cooperatively facilitate cytochrome C release and cell death. Cell Death Differ 2014; 21 (1), 172-184.

Song, X., Seo, J., Baameur, F., Vishnivetskiy, S.A., Chen, Q., Kook, S., Kim, M., Brooks, E.K., Altenbach, C., Hong, Y., Hanson, S.M., Palazzo, M.C., Chen, J., Hubbell, W.L., Gurevich, E.V., Gurevich, V.V. Rapid degeneration of rod photoreceptors expressing self-association-deficient arrestin-1 mutant. Cell Signal 25, 2613-2624 (2013).

Zhan X, Kaoud TS, Kook S, Dalby KN, Gurevich VV.  JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases.  J Biol Chem 2013 ; 288 (40), 28535-28547.

Breitman M, Kook S, Gimenez LE, Lizama BN, Palazzo MC, Gurevich EV, Gurevich VV. Silent scaffolds: inhibition of JNK3 activity in the cell by a dominant-negative arrestin-3 mutant. J Biol Chem 2012; 287 (23), 19653-1966

Gimenez LE, Kook S, Vishnivetskiy SA, Ahmed MR, Gurevich EV, Gurevich VV.  Role of receptor-attached phosphates in binding of visual and non-visual arrestins to G protein-coupled receptors.  J Biol Chem 2012; 287 (12), 9028-9040

Coffa S, Breitman M, Hanson SM, Callaway K, Kook S, Dalby KN, Gurevich VV. The effect of arrestin conformation on the recruitment of c-Raf1, MEK1, and ERK1/2 activation. PLoS One. 2011; 6 (12), e28723.

Ahmed MR, Zhan X, Song X, Kook S, Gurevich VV, Gurevich EV.  Ubiquitin Ligase Parkin  Promotes Mdm2-Arrestin Interaction but Inhibits Arrestin Ubiquitination.  Biochemistry 2011;  50 (18), 3749-63

Ahmed MR, Berthet A, Bychkov E, Porras G, Li Q, Bioulac BH, Carl YT, Bloch B, Kook S,  Aubert I, Dovero S, Doudnikoff E, Gurevich VV, Gurevich EV and Bezard E.  Lentiviral  overexpression of GRK6 alleviates L-dopa-induced dyskinesia in experimental Parkinson’s disease.  Sci Transl Med  2010, 2,  28ra28

 

Papers describing previous work:

Kook S, Exton JH. Identification of Interaction Sites of Protein Kinase Ca  on Phospholipase D1. Cell Signal. 2005 Nov;17(11):1423-1432.

Kim W, Kook S, Kim DJ, Teodorof C, Song WK. The 31-kDa caspase-generated cleavage product of p130Cas functions as a transcriptional repressor of E2A in apoptotic cells. J Biol Chem. 2004 Feb 27;279(9):8333-8342.

Kook S, Kim DH, Shim SR, Kim W, Chun JS, Song WK. Caspase-dependent cleavage of tensin induces disruption of actin cytoskeleton during apoptosis. Biochem Biophys Res Commun. 2003 Mar 28;303(1):37-45.

Do Hoon Kim, Soo Jeon Choi, Seunghyi Kook, Wook Kim and Woo Keun Song. Phosphorylation-dependent cleavage of p130cas in apoptotic Rat-1 cells. Biochem. Biophys. Res. Commun. 2003, 300. 141-148.

Shim SR, Kook S, Kim JI, Song WK. Degradation of focal adhesion proteins paxillin and p130cas by caspases or calpains in apoptotic Rat-1 and L929 cells. Biochem Biophys Res Commun. 2001 Aug 24;286(3):601-608.

Kook S, Shim SR, Choi SJ, Ahnn J, Kim JI, Eom SH, Jung YK, Paik SG, Song WK. Caspase-mediated cleavage of the p130cas in etoposide- induced apoptotic rat-1 cells. Mol Biol Cell. 2000 Mar;11(3):929-939.

Kook S, Shim SR, Kim JI, Ahnn JH, Jung YK, Paik SG, Song WK. Degradation of focal adhesion proteins during nocodazole-induced apoptosis. Cell Biochem. Funct. 2000 Mar;18(1):1-7

Kyeong-Yeop Moon, Seunghyi Kook, Woo Keun Song, Hyockman Kwon, Chin Ha Chung and Man Sik Kang. Expression and functional analysis of the 66-kDa protien, a matrix assembly receptor of fibronectin during myogenesis. Mol. Cells. 1996, 6. 325-333.