Structural Highlights from Pegan Laboratory
Regulation of the Human Innate Immune System
To gain a greater understanding of the mammalian innate immune response and how it is modulated, as well as develop new therapeutic templates for emerging diseases. Our on-going intent is to investigate the anti-viral type I response through the structural and kinetic study of proteases and ligases involved in the immune response signaling pathway. Through this research a better understanding of the role these proteins play in cellular regulation of the innate anti-viral immune response will occur. Currently, we are working with a model system from Crimean-Congo Hemorrhagic Fever virus (CCHFV), which in itself is a dangerous emerging pathogen exhibited by its recent deadly outbreaks in Turkey and India. Furthermore, CCHF has spread across Asia and Africa and is present particularly in the Middle East transmission. Danger to US was highlighted in 2009 by the death of a US Soldier serving in Afghanistan by CCHFV.
Discovery of new antibiotics for use against Tuberculosis
Tuberculosis (TB) is one of the most prevalent infections in the world, and a leader among the causes of mortality in developing countries. The World Health Organization estimates one third of the world’s population is infected with latent TB. With a rise in new cases of active TB and emergence of multidrug resistant strains, MDR-TB and XDR-TB, there is a strong need for development of antibiotics targeting novel pharmacological targets within Mycobacterium tuberculosis. One such drug target for TB is M. tuberculosis’ class II fructose 1,6-bisphosphate aldolase (MtFBA), which is required for bacterial survival and is non-existent in humans. Inhibitors have been developed for class II FBAs; however, they lack specificity and drug-like properties, preventing their translation into viable therapeutic leads. Optimization of these compounds has been historically hindered by a lack of MtFBA structural information and viable drug-like leads. Using the latest in Structural biology and drug discovery techniques, we intend to generate novel chemical compounds that have potent anti–bacterial features for therapeutics targeting TB and other pathogenic bacteria.