Lara Skibbie, Graduate Student, Dowd Lab, GW Department of Chemistry

The Department of Chemistry Presents:  Lara Skibbie, Graduate Student, Dowd Lab, GW Department of Chemistry

Antibiotic resistance is a burgeoning public health threat, with countless pathogens rapidly evolving to evade current therapeutics. Mycobacterium tuberculosis (Mtb), Plasmodium falciparum (Pf), and the ESKAPE pathogens are at the forefront of this global issue. Mtb causes tuberculosis, the leading cause of death from a single infective agent. The malaria parasite Pf is responsible for over 600,000 deaths annually. Together, the six ESKAPE pathogens are the most likely cause of nosocomial infections. Novel anti-infective agents must be developed to combat all these species. A commonality amongst the pathogens may provide a singular solution to address this broad issue. In recent years, the coenzyme A (CoA) pathway has garnered significant interest in the world of drug discovery. CoA is an essential cofactor involved in myriad biochemical processes ranging from cellular energy production to cell structure development. A universal CoA biosynthetic pathway exists in all prokaryotic and eukaryotic species, but key differences between the bacterial and human pathways allow for the development of a selective inhibitor. In particular, distinctive features of the binding pocket of the PPCS enzyme within the CoA pathway provides a unique opportunity for the design of tight binding inhibitors that will preferentially inhibit CoA biosynthesis in prokaryotic species, exhibiting a bactericidal effect. To this end we have synthesized several structures that will help us probe the PPCS binding pocket, making progress towards the development of highly specific PPCS inhibitors.

BIO

Lara received her B.S. in Physiology and Neurobiology from University of Maryland. After graduating, she worked in the biotechnology industry for two years prior to joining the chemistry department at George Washington University. Her research in the Dowd group focuses on the development of inhibitors to the CoA biosynthetic pathway in various pathogens.