OT:USC School of Pharmacy Gets $5 Million Grant

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Tapping into a fungus to kill a fungus.......

USC School of Pharmacy Gets $5 Million Grant

LA Downtown News Online - Los Angeles,CA*

Funds Will Aid Research Into 'Novel Compounds'

Clay C. C. Wang.

by Kukla Vera

http://www.ladowntownnews.com/articles/2008/06/09/health2/health03.tx

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Clay C. C. Wang, assistant professor in the USC Department of

Pharmacology and Pharmaceutical Sciences, is leading the

university's effort on research that seeks natural compounds with

the potential to be used as new chemotherapies and antimicrobials.

The effort to find a compound that may serve as the basis of the

next new wonder drug has kicked off an extensive search.

" This is tough work and takes an army to accomplish it, " said Wang.

Wang and his colleagues have found support for their search at the

National Institutes of Health, which has awarded them a $4.9 million

grant to fund a three-site project to mine the Aspergillus nidulans

secondary metabolome in search of promising new therapeutics.

The metabolome is the complete set of small-molecule metabolites

found within a biological sample, such as a single organism. The

secondary metabolome is a subset consisting of beneficial molecules

produced naturally by the organism.

Wang's collaborators are principal investigators Berl Oakley of Ohio

State University and Keller from the University of Wisconsin-

Madison.

The project will delve into the metabolite pathways of A. nidulans -

a form of fungi related to the fungus from which the cholesterol-

lowering drug lovastatin (marketed as Mevacor) is derived, Wang said.

The project hypothesizes that the next frontier of natural product

discovery is not unknown to us but instead 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, " said Wang. " 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. Further, the tools and

methods developed in this 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, he hopes, ultimately identifying the

various new compounds.

The five-year grant will be divided among the three

institutions. " This collaborative approach realizes the best of

three disciplines and takes us closer to finding the next best

compound, " said Wang.

Wang's research is also supported by another NIH grant, an American

Cancer Society award and a grant from the State of California.

Article courtesy of USC HSC Weekly.