David L. Williams, PhD

I have more than 20 years of experience studying the biochemistry and molecular biology of schistosome parasites with extensive experience with both in vitro and in vivo methods. I have made numerous important contributions including the identification of the worm’s major redox enzymes, the central importance and essential nature of thioredoxin glutathione reductase (TGR) in worm redox biochemistry and the worm’s dependence on peroxiredoxins for H2O2 neutralization. We conducted the first high-throughput screen against a parasite drug target and identified oxadiazole-2-oxides as potential schistosomicidal compounds. I have contributed to the basic understanding of the catalytic mechanisms and structures of flavoenzymes and peroxiredoxins. I have pioneered studies on a novel protein, phytochelatin synthase, involved in detoxification of xenobiotics and heavy metals in parasitic worms. I have also initiated studies on an uncharacterized cytochrome P450 protein in the worm. We have recombinantly expressed Schistosoma mansoni cytochrome P450, screened a preliminary series of cytochrome P450 inhibitors, and found that RNA interference silencing of cytochrome P450 in larval worms is lethal, indicating that cytochrome P450 is an essential and druggable protein. Unlike humans, who have 57 cytochrome P450 genes, parasitic helminths have only one gene. I am currently program director for the Division of Immunology and Microbiology at Rush and am actively engaged in mentoring graduate students and postdoctoral fellows.