Kyungsoo Shin, PhD

Assistant Professor

Locations

Biophysics
MFRC 2060

Contact Information

Education

Cell and Molecular Biology of Cancer Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 2017-2022
PhD, Dalhousie University, Halifax, NS, Canada, 2017
BS, Dalhousie University, Halifax, NS, Canada, 2011

Research Interests

As a member of the Marassi lab, my research interest is in determining proteins' structures (or lack thereof) in their native environment and how the structures and conformational dynamics regulate their interactions with other molecules and, thus, their known functions. My interest leads me to use a combination of structural biology and biophysical technologies, including solution- and solid-state NMR spectroscopy, x-ray crystallography, and cryo-EM. In addition, we routinely develop and carry out biochemical and cellular assays to fully decipher the protein structure-function correlations. I am currently focused on the characterization of a protein called vitronectin, a regulator of many physiological processes, specifically in relation to age-related macular degeneration and Yersinia pestis pathogenesis (see below).

Research Project
Determining the disease mechanism of dry AMD and the role of vitronectin in this disease
Dry age-related macular degeneration (AMD) is one of the leading causes of blindness in older patients. Its hallmark is the build-up of insoluble deposits that perturb the transfer of nutrients and waste between photoreceptors and the choroid capillaries, leading to their degeneration. The spherical molecules (i.e., spherules) that make up the deposit contain cholesterol-enriched lipid cores with an initial coating by hydroxyapatite (calcium phosphate biomineral) and a final top layer of proteins. Vitronectin is a serum protein that regulates many physiological processes, including immune response and lipid metabolism. It has long been associated with AMD and is commonly found within insoluble deposits. Vitronectin can either evenly or diffusely surround the spherules, suggesting that it may mediate spherule formation. However, its role in pathogenesis remains challenging to decipher. I will use multiple and complementary biophysical techniques to elucidate the role of vitronectin in AMD at the molecular level. I aim to map the molecular binding sites to gain insight into vitronectin’s ability to recruit spherule constituents and begin associating different protein regions with known functions. Lastly, I am working on assembling AMD spherules in vitro to characterize vitronectin’s role and screen molecules that can mediate pathogenesis.

Y. pestis pathogenesis mechanism and involvement of vitronectin
Y. pestis, the causative agent of plague, is an invasive blood pathogen that poses a high risk to public health, given its high pathogenicity, dissemination rate, and mortality. It is known to recruit various human host proteins to survive and thrive in serum. Notably, this bacterium also recruits vitronectin from the serum using its membrane protein, Ail (attachment invasion locus), and membrane protease Pla (plasminogen activator); the latter can also cleave vitronectin to regulate its function. The two membrane β-barrel proteins are critical for disease pathogenesis, and it is hypothesized that vitronectin recruitment may play an important role. We have the capability to produce all the players mentioned using recombinant protein technology and study them in their near-native environments, giving us a unique opportunity to characterize this system. I am interested in deciphering the molecular interplay between them under pathophysiological conditions. I aim to characterize the structural mechanism behind vitronectin recruitment by the Y. pestis membrane proteins, the Pla-mediated processing of vitronectin, and their functional consequences.

(Gopinath T, Kraft A, Shin K, Wood NA, Marassi FM.) bioRxiv. 2024 Jul 24 PMID: 39211063 PMCID: PMC11360888 08/31/2024
(Gopinath T, Shin K, Tian Y, Im W, Struppe J, Perrone B, Hassan A, Marassi FM.) J Struct Biol. 2024 Mar;216(1):108061 PMID: 38185342 PMCID: PMC10939839 SCOPUS ID: 2-s2.0-85182378487 01/08/2024
(Shin K, Kent JE, Aleshin AE, Tian Y, Fujimoto LM, Singh C, Marassi FM.) Biophys J. 2023 Feb 10;122(3S1):467a PMID: 36784398 02/15/2023
(Tian Y, Shin K, Aleshin AE, Im W, Marassi FM.) Biophys J. 2022 Oct 18;121(20):3896-3906 PMID: 36056555 PMCID: PMC9674982 SCOPUS ID: 2-s2.0-85137693880 09/04/2022
(Kent JE, Fujimoto LM, Shin K, Singh C, Yao Y, Park SH, Opella SJ, Plano GV, Marassi FM.) Biophys J. 2021 Feb 02;120(3):453-462 PMID: 33359463 PMCID: PMC7895992 SCOPUS ID: 2-s2.0-85099124668 12/29/2020
(Shin K, Kent JE, Singh C, Fujimoto LM, Yu J, Tian Y, Im W, Marassi FM.) Proc Natl Acad Sci U S A. 2020 Aug 04;117(31):18504-18510 PMID: 32699145 PMCID: PMC7414086 SCOPUS ID: 2-s2.0-85089166480 07/24/2020
(Shin K, Lechtenberg BC, Fujimoto LM, Yao Y, Bartra SS, Plano GV, Marassi FM.) Sci Adv. 2019 Sep;5(9):eaax5068 PMID: 31535027 PMCID: PMC6739113 SCOPUS ID: 2-s2.0-85072215989 09/20/2019
(Shin K, Landsman M, Pelletier S, Alamri BN, Anini Y, Rainey JK.) Amino Acids. 2019 Mar;51(3):395-405 PMID: 30430332 PMCID: PMC7101949 SCOPUS ID: 2-s2.0-85056464644 11/16/2018
(Kenward C, Shin K, Rainey JK.) Chemistry. 2018 Mar 07;24(14):3391-3396 PMID: 29342326 SCOPUS ID: 2-s2.0-85041903173 01/18/2018
(Shin K, Kenward C, Rainey JK.) Compr Physiol. 2017 Dec 12;8(1):407-450 PMID: 29357134 PMCID: PMC5821487 SCOPUS ID: 2-s2.0-85043302048 01/23/2018
(Shin K, Sarker M, Huang SK, Rainey JK.) Sci Rep. 2017 Nov 13;7(1):15433 PMID: 29133807 PMCID: PMC5684411 SCOPUS ID: 2-s2.0-85034078489 11/15/2017
(Shin K*, Kent JE*, Marassi FM.) NMR Spectroscopy for Probing Functional Dynamics at Biological Interfaces. The Royal Society of Chemistry. . Shin K*, Kent JE*, Marassi FM. Membranes, Minerals and Magnets: Application of NMR Spectroscopy to Biological Interfaces. In: Bhunia A, Atreya HS, Sinha N, editors. NMR Spectroscopy for Probing Functional Dynamics at Biological Interfaces. London: Royal Society of Chemistry; Aug 2022. p. 496-529. 08/27/2022

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