SBMS Trainee: Matthew Wipperman
Graduate Advisor: Nicole Sampson
Graduate Program: Chemistry
I am currently a rising third year graduate student in the Department of Chemistry. As an undergrad, I majored in chemistry at Franklin & Marshall College, and my research there involved organic synthesis and physical-organic chemistry. At Stony Brook, I work in the field of chemical biology, studying the intricacies of cholesterol metabolism by the pathogenic bacterium Mycobacterium tuberculosis (Mtb). Specifically, I have been working on a project studying acyl-CoA dehydrogenase genes and their corresponding enzymatic products from Mtb. We recently demonstrated that these genes evolved in a very unique way in order to accommodate a large steroid carbon framework. My proposed SBMS research project aims build upon this finding and are two-fold. First, I hope to determine the relationship between attenuation of cholesterol metabolism by Mtb and the host infection. By synthesizing an azasteroid drug that specifically inhibits the Mtb enzyme that initiates cholesterol metabolism, 3ß-hydroxysteroid dehydrogenase, I hope to elucidate the resultant chemotype in a mouse infection model. Second, I hope to explore increasing mycobacterial susceptibility to current anti-tubercular drugs through inhibition of cholesterol metabolism. Generally drug combination therapy is the most effective route to fully eliminate bacterial disease (or in many cases, just to see an effect), so we plan to test how current drugs work on the Mtb phenotype with an attenuated ability to degrade cholesterol. My PhD mentor is Nicole Sampson, who is currently the chair of the Department of Chemistry, and also an expert in the study of steroid metabolism by Mtb. My clinical co-advisor is Sharon Nachman, M.D., who is an expert in both tuberculosis disease, drug dosing, as well as the Vice Chair of the TB scientific committee for the NIH funded maternal child HIV network, IMPAACT.