Harshit Kolisetty
Interrogating the Mechanism of Small Molecule Inhibitors for Cardiovascular Disease
A leading factor of atherosclerosis is the overexpression of the protein PCSK9, which leads to the excessive degradation of low-density lipoprotein receptor (LDLR) and buildup of LDL plaques in the bloodstream. This project involves diving into the inhibitory mechanism of small molecule drugs against PCSK9 as an oral therapeutic against high blood pressure. The use of computational docking screens and other biochemical and biophysical tests will help elucidate the mechanism of action of these compounds. In addition, the use of a gene editing system in liver cells will help identify the physiologic mediators of lysosomal trafficking. Identifying these factors will allow us to identify PCSK9’s tissue specificity, cryptic causes of familial hypercholesterolemia, candidate targets for lipid lowering, and understand the effect of PCSK9 on non-LDLR proteins. This work is essential in the development of a novel targeted protein degradation platform and creating a more accessible treatment to the world’s leading cause of death.
Message To Sponsor
I am very appreciative of this opportunity that has allowed me to invest so much of my time working on this research project which has ended up being so fruitful with many positive results for the lab.