NIH Grant Goes to USC Pharmacy School

Clay Wang leads USC’s search for natural compounds with potential as new chemotherapies and antimicrobials.
By Kukla Vera
A collaborative approach "takes us closer to finding the next best compound," said assistant professor Clay Wang.

Photo/Lee Salem Photography Inc.
Today’s pharmaceutical war chest is always in search of the next great compound. Among the best places that scientists search for tomorrow’s wonder drugs are the farthest corners of the earth and the depths of the oceans.

That tough work takes an army to accomplish it, according to Clay C.C. Wang, assistant professor at the USC School of Pharmacy.

Wang contends that one must construct a synergistic approach to efficiently mine the world, using cutting-edge tools of genomics, molecular genetics and natural products chemistry.

Wang and his colleagues have found support for their approach at the National Institutes of Health, having been awarded a three-site, program project grant “to mine the Aspergillus nidulans secondary metabolome” in search of promising new therapeutics. Wang’s collaborators are the overall project investigator Berl Oakley of Ohio State University and Nancy Keller of the University of Wisconsin-Madison.

“The Aspergillus nidulans sounds like a different language,” Wang said. “Actually most people know about Aspergillus fungi the aspergillus terreus gave us lovastatin, the cholesterol medication commonly marketed as Mevacor.

“Our project will look at a different Aspergillus species, the secondary metabolite pathways of A. nidulans.”

The project hypothesizes that the next frontier of natural product discovery is not unknown to us but instead is undiscovered in the genomes of organisms that have been looked at in laboratories for decades.

Looking at other pathways, or secondary pathways, of these organisms requires a collaborative approach using the latest molecular genetic tools, increased understanding of the regulation of these secondary metabolites and analytical tools designed to identify these new pathways. These skills are not to be found under one roof.

“Together, we’ll be able to elucidate the products of these pathways, building on each other’s work,” Wang said. “We expect the project to generate a substantial number of new natural products for development as therapeutics.”

The researchers see potential for these new compounds as chemotherapy and antimicrobial agents. In addition, the tools and methods developed in this program project can be translated to other fungal genomes as they become known.

Wang’s part of the project utilizes his expertise in natural product chemistry to analyze Aspergillus strains that will be provided by his collaborators. Wang will purify and elucidate the structure by sequencing the genome and hopefully identify the various new compounds.

The five-year grant of $4,910,613 will be divided among the three institutions. According to Wang, “This collaborative approach realizes the best of three disciplines and takes us closer to finding the next best compound.”

Wang’s research is supported by another NIH grant, an American Cancer Society award and a grant from the State of California.