Research in the Campbell Lab

Drug discovery for Sleeping Sickness, a neglected tropical disease
My current research is focused on drug discovery for Sleeping sickness, a lethal disease caused by infection with Trypanosoma brucei. It has a global impact similar to multiple sclerosis (another terrible disease). The World Health Organization has identified Sleeping sickness as one of several neglected tropical diseases in urgent need of new drug discovery.

The main project is a collaboration with the Kinetoplastid Drug Discovery Unit at GlaxoSmithKline in Tres Cantos, Spain. I co-lead the project with Harry de-Koning (University of Glasgow) and Michael Pollastri (Northeastern University). The Tres Cantos Open Lab Foundation is funding two postdoctoral fellows, Sofia Olego-Fernandez and Gopal Jadhav, to conduct screening, hit validation, and hit optimization chemistry in GSK’s Open Lab in close collaboration with a team of GSK drug discovery experts. The focus on this work is a pair of phosphodiesterase enzymes (PDEB1 and PDEB2) that were initially shown by Thomas Seebeck’s lab to be essential for survival of the pathogenic life stage of T. brucei.

The project in Tres Cantos builds on results from the NIH R01 grant awarded to Michael Pollastri and me for validation and initial lead discovery against the PDEB enzymes, and the recent success of crystallography studies done in collaboration with Rebecca Page (Brown University) and Nick Bland during his time as a PhD Research Scientist in my lab. This success is being augmented with structural biology and modeling studies involving scientists from Schrodinger.

The origin of this work was an analysis of the first reported genome for T. brucei. This analysis revealed numerous genes encoding proteins similar to drug targets already exploited by industry for other diseases. Prioritization of these targets with Preeti Bais (now at Jackson Laboratory for Genomic Medicine), Greg McAllister (now at Novartis), and Michael Pollastri (Northeastern) led us to focus on the PDEB enzymes.

 

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