McNair Scholar 2024 - Tomas I. Sepulveda
Tomas I. Sepulveda is a junior at the University of Minnesota, majoring in Neuroscience and pursuing requirements to major in Chemistry. His research interests include the development of safer therapeutics for pain management and new therapeutics for inflammation-driven diseases. Tomas has plans to pursue a Ph.D. in Chemistry after graduating.
Quote from Tomas Sepulveda
My dream is to help others my way: combining science with empathy. Receiving a Ph.D. in Chemistry would be an important milestone to my (hopefully) long journey advocating for and educating others on pain management.
Research project
Synthesis of Novel 1,2,3-Triazole-Based HDAC/BRD4 Inhibitors for Inflammatory Pain
Abstract
Inflammation has been linked to pain through upregulation of pro-inflammatory cytokines which increase neurons’ sensitivity to painful stimuli. Additionally, epigenetic mechanisms can modulate inflammation by regulating the expression of cytokines, correlated through high levels of histone acetylation near their promoters. Histone deacetylases (HDACs) and Bromodomain and Extraterminal (BET) proteins, which either hydrolyze or bind to acetylated lysines, are attractive therapeutic targets for a range of inflammation-driven diseases. Simultaneous targeting of these proteins has emerged as an attractive therapeutic approach. While new, SUM52 has been recently tested as a fusion of BET and HDAC inhibitors, iBET762 and Vorinostat. The goal of this study is to add to the library of dual HDAC/BET inhibitors with a triazole-based inhibitor, compound 7, developed in the Pomerantz lab. For this study, the BET inhibitor NV1127 and the HDAC inhibitor based on Vorinostat are being synthesized and linked. Progress towards these goals will be presented.
Faculty mentor
Dr. William C.K. Pomerantz is a professor in the Department of Chemistry, having completed his Ph.D. at the University of Wisconsin-Madison in 2008. Dr. Pomerantz’s research focuses on the development of chemical and biological approaches for probing and modulating protein-protein interactions. Areas of innovation have included the application of protein-observed 19F NMR (PrOF NMR) for fragment-based drug discovery, development of new epigenetic inhibitors of BET and non-BET bromοdomains, the design of fluorinated molecules for 19F MRI, and sustainable organofluorine chemistry. Dr. Pomerantz has published in multiple research journals and has received many awards, mentoring post-doctorates, graduate students, and undergraduates alike.