October 6, 2009
Faculty members at the UNC Eshelman School of Pharmacy have been awarded grants totaling more than $2 million from the National Institutes of Health through the American Recovery and Reinvestment Act, commonly known as the economic stimulus bill or recovery act. At the UNC Eshelman School of Pharmacy, we believe we have a special obligation to our fellow citizens to report on the projects funded with this money. This page will be updated as new projects are funded.
Stephen Frye, PhD, “Discovery of Small Molecule MBT Domain Antagonists”
Frye received a two-year $873,000 challenge grant to study proteins involved in chromatin regulation. He will develop molecular probes to explore the regulation of the cellular genetic material called chromatin and how chromatin’s control of gene expression and gene silencing is relevant in normal and disease biology. When the proteins that control chromatin are deranged, cancer can develop.
Frye is director of the Center for Integrative Chemical Biology and Drug Discovery and a professor in the Division of Medicinal Chemistry and Natural Products. He is also a member of UNC Lineberger Comprehensive Cancer Center.
Andrew Lee, PhD, “Dynamic Networks and Mechanisms of Allosteric Communication in Proteins”
Lee received $97,556 to support his work studying the internal movement and communication of protein molecules. Proteins are the body’s molecular machines and are popular targets for drugs as blocking a protein’s function can slow or stop a biological process. Lee studies how proteins transmit information about what is happening at one site on their structure to more distant points along the molecule. This communication can affect structure, movement, and energy at other points on the protein, including potential drug binding sites.
Lee is an associate professor in the Division of Medicinal Chemistry and Natural Products.
Mary Paine, PhD, “Mechanisms Underlying Drug-Diet Interaction”
Paine has been awarded $342,592 to study whether milk thistle products should be avoided when taking certain medications. Milk thistle extracts, are taken by many people in hopes of preventing liver damage and as a treatment for liver diseases such as hepatitis and cirrhosis. Because milk thistle acts on the liver where many drugs are metabolized, there is the potential for it to interact or interfere with those drugs.
Paine an assistant professor in the Division of Pharmacotherapy and Experimental Therapeutics,
Alex Tropsha, PhD, “Predictive QSAR Modeling”
Tropsha has received $730,789 to support his work in developing a faster, more accurate drug-design technique based on cheminformatics, an approach that mixes the disciplines of chemistry and computer science. Here is his description of his project in his own words.
“There are two major computational approaches to drug design: ligand based and structure based. The former only uses the information on organic molecules tested in experimental assays that are considered relevant; i.e., molecules found active in such assays are expected to be clinical candidates against specific diseases (e.g., active inhibitors of HIV protease are potential drugs combating HIV). The parent grant of this new application is aimed at the development of novel computational approaches for ligand-based drug design based on the concepts of a research discipline known as cheminformatics.
The alternative approach is structure-based design, which utilizes the knowledge of experimentally determined (by x-ray or NMR) three-dimensional structure of protein or nucleic-acid targets (e.g., HIV protease). This information is used to discover organic molecules that are stereochemically complementary to the active sites of the target proteins. The computational approaches used in this case, specifically docking (i.e., simulation of ligand binding to the receptor) and scoring, are part of a discipline known as structural bioinformatics.
My new proposal bridges these two approaches in a new way. Specifically, we employ cheminformatics concepts but apply them to characterize three-dimensional binding sites of protein structure. This approach is expected to be orders of magnitude faster than current structure-based methodologies yet rival them in accuracy.”
Tropsha is chair of the Division of Medicinal Chemistry and Natural Products and the K. H. Lee Distinguished Professor.
The University has set up a Web page with details on ARRA grants at Carolina. More information about NIH’s ARRA grant-funding opportunities can be found at http://grants.nih.gov/recovery/. To track the progress of HHS activities funded through the ARRA, visit www.hhs.gov/recovery.
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