My Introduction to the Brackenridge Fellowship

Hi all, and welcome! My name is Sara Zdancewicz, an undergraduate majoring in Statistics and Biology, and a current recipient of the Brackenridge Fellowship for the upcoming summer months. A little bit about me— I plan on graduating this December and will be applying to grad schools for Fall 2023 admittance in either Structural Biology or Biophysics programs at quite a few schools in quite a few places around the country. Personally, I’m excited to see how all the additional resources I can access through the Brackenridge Fellowships, such as scholarship mentoring, and workshops about grant writing and presenting data at a conference, help me apply my research expertise and make me a stronger grad applicant.

Visually, this is the effect that the drug we are testing (labeled C2/C74) has on blood vessel growth specifically after eye injuries

My research for the summer is being conducted in the VanDemark lab, which I have been a researcher in for the past 3 and a half years. The focus of my research is characterizing drug-protein interactions between novel drugs being developed to treat pathologic angiogenesis and their protein targets in the body. Pathologic angiogenesis is essentially when blood vessel growth occurs in areas and at times it should not be occurring, such as after eye injuries leading to blindness (shown above), or in cancer patients where networks of vessels supply tumors with the blood and nutrients to allow them to grow. Currently the drugs have been shown to be effective and limit blood vessel growth in cell-based assays and mouse models, but are not yet potent enough for clinical testing or human use. Where my research comes in is with the optimization of these drugs to make them more effective. We know that they work and are able to limit vessel growth, but the protein target that these drugs bind to in the body, and how they bind to it are still unknown. Without this knowledge, there are no efficient or convenient ways to improve drug design other than mass amounts of computational modeling and somewhat educated guesses. My goal this summer is to identify the protein target that the drugs bind to, and by using x-ray crystallography techniques, to provide an experimentally determined model of the protein-drug complex structure that we can use to design more potent drugs by identifying important contact points. A secondary goal of mine will be setting up and utilizing a screening system to quickly determine future compound efficacy in comparison to the original drugs. By using a few biochemical assays that look at things like protein stability in the presence of a ligand, or measure heat expelled upon drug-protein binding, I can quantify the binding affinity between drug and compound. As drug efficacy increases, we will see binding affinity increase as well, and the concentration of administered drug necessary for it to be effective in patients would decrease (helpful in limiting any adverse side effects!). By developing drugs to treat these cases of pathologic angiogenesis, we can provide people with better clinical outcomes in a variety of situations, and can introduce new mechanisms of treatment to patients for whom preexisting therapeutics may not have been effective, which is why I think this research is important and worth pursuing.

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