David P Rotella
My lab is investigating structure activity relationships in a natural product that has activity as an inhibitor of HSP90. HSP90 is a key chaperone protein that plays a role in apoptosis, protein trafficking and folding. Inhibitors have been shown to be useful in preclinical models of neuroprotection and cancer. We are working with scientists at the University of Rochester to study new compounds and investigate their activity.
Protein kinase inhibitors for parasitic diseases
Collaborative drug discovery research is being carried out with Professor John Siekierka and coworkers in his laboratory and with researchers at Celgene Incorporated. Colleagues in my lab are synthesizing new analogs of a lead structure as potential protein kinase inhibitors. These compounds are being evaluated in Professor Siekierka's lab for activity against the target kinase and against the parasite for activity. Scientists at Celgene carry out more detailed studies with selected new molecules to evaluate their drug like properties. Together the team hopes to be able to identify molecules suitable for testing in humans to treat parasitic diseases.
Botulinum protease inhibitors
Working with scientists at the US Army Medical Research Institute for Chemical Defense my lab is synthesizing inhibitors of botulinum protease, an enzyme that causes muscle paralysis upon exposure. This enzyme is secreted by a bacterium that can be used as a potential bioterror weapon. Our aim is to improve the properties of lead structures to the point where these molecules would be available for use by military or civilian healthcare workers in the event this organism is released.