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Biophysics
Kyungsoo Shin_Academic Profile

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.

Publications

Publications of Kyungsoo Shin PhD from the Faculty Collaboration Database

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