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

With a death toll surpassing 1.6 million per year, tuberculosis (TB) caused by the bacteria Mycobacterium tuberculosis (Mtb), is widely regarded as the one of the most lethal infections to threaten our society today. Historically, the disease has been effectively treated through a cocktail of anti-TB drugs. However, various factors have led to the development of drug resistant TB strains. Mtb is not the only drug resistant infective species posing a major threat to global health. The acronym ‘ESKAPE pathogens’ refers to six nosocomial pathogens associated with the highest risk of mortality among antibiotic resistant bacteria. Novel anti-infective agents must be developed to combat all of these bacterial 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, as well as make progress towards the synthesis of highly specific PPCS inhibitors.

BIO

Lara graduated from the University of Maryland in 2017 with a B.S. in Physiology and Neurobiology. Prior to GW, she worked as a process chemist at an electronic design firm, and subsequently as a research scientist at a biotechnology company. Since joining the Dowd lab in 2020, Lara has been involved in developing inhibitors to both the CoA and DXR biosynthetic pathways.

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