NIH Funds BU-CMD to Develop New Antifungal Compounds

The National Institutes of Health (NIH) has awarded a four-year grant to Center for Molecular Discovery researcher Lauren Brown and collaborators Leah Cowen [http://individual.utoronto.ca/cowen/] (University of Toronoto) and Luke Whitesell [http://lindquistlab.wi.mit.edu/members/] (Whitehead Institute for Biomedical Research at MIT) on “Targeting Hsp90 in crytococcal fungal pathogenesis.” The assembled team combines expertise in fungal biology (Cowen), medicinal chemistry (Brown) and pharmacology/experimental therapeutics (Whitesell) with the goal of developing drug-like small-molecule probes for use in studying disease mechanisms of the fungus Cryptococcus.

 

Invasive Cryptococcus infections pose a grave threat to human health and have enormous economic consequences. Cryptococcal meningitis, the major clinical manifestation of the disease, has a 100% mortatlity rate if left untreated. Even with the best available therapies, mortality rates remain high at 35-40% due to a limited number of drug classes available, and compromised usefulness of these drugs caused by both dose-limiting toxicity and the emergence of high-grade antifungal drug resistance.

 

In this project, the team will collaborate to develop small molecule chemical compounds to study a critical molecular mechanism that supports both fungal virulence and the onset of drug-resistance. These compounds will also impact clinical care by serving as promising leads for the future development of new, more effective antifungal drugs.