Li & Brown Awarded NIH Grants
Li Awarded Two NIH Grants
Wei Li, PhD, Associate Professor and Director of the Nuclear Magnetic Resonance (NMR) Facility at UTHSC, was recently awarded two NIH grants and a UT Research Foundation grant totaling $1.8 million. An NIH grant titled "Discovery of novel thiazole analogs for treating advanced melanoma" will fund research into developing new drugs to treat melanoma, which has rising incidence in the United States and is the most deadly type of skin cancer. While early stage melanoma can be cured by surgical removal, once metastasized, it is very difficult to treat and the median survival is only a few months.
Working with Drs. Duane Miller, Ram Mahato, James Dalton (GTx Inc.), and Yi Lu (College of Medicine), Dr. Li aims to design and synthesize new classes of small molecules targeting tubulin polymerization, and selectively target only melanoma tumor cells. Tubulin is a well-validated target with at least three distinct binding sites for drugs to interact: the paclitaxel binding site (e.g., Taxol, epothilones); the vinblastine binding sites (e.g. vinblastine, vincristine); and the colchicine binding site. There are many FDA-approved, very successful anticancer drugs targeting the first two sites, but currently there is no FDA-approved drug targeting the colchicine site for cancer treatment. Three of the major limitations for existing cancer drugs targeting tubulin polymerization are the development of multidrug resistance, poor aqueous solubility, and systematic toxicity (especially neurotoxicity). Preliminary studies with these new compounds suggest that these new agents will help to alleviate these major limitations for more effective treatment for melanoma.
Li's second NIH grant titled "Acquisition of a 400M NMR with an autosampler" will be used to fund a state-of-the-art 400 MHz NMR instrument, which will allow researchers to "see" the exact structures of molecules. With this technology, researchers will be able to ensure that they have created the intended molecules and are able to pinpoint the exact structure of mysterious metabolites that a drug produces in the body. The new instrument will be installed in late May to early June; it will be the only one at UTHSC, and will significantly enhance many of the biomedical research programs.
The UT Research Foundation awarded Li a grant titled "Preclinical studies of new vitamin D analogs as potential agents for arthritis." The importance of sufficient vitamin D (such as Calciferol) in human bodies has been well recognized. Vitamin D has broad benefits to human health, including bone formation, cancer prevention, and anti-inflammation effects. However, the users of existing vitamin D analogs suffer from a severe side effect called hypercalcemia , which could result in calcification of soft tissues, organ failure, or even death. Li and his cohorts have isolated many new biologically active vitamin D metabolites and elucidated their complete molecular structures. These analogs have shown excellent efficacy in a variety of disease models, especially in arthritis, as recently tested by Dr. Arnold Postlethwaite (College of Medicine and VA hospital), and do not have the hypercalcemic side effect as tested by Drs. Michal Holick and Tai Chen at Boston University. Working with Drs. Slominski, Miller, and Postlethwaite, they are currently designing and synthesizing new analogs to expand this class of compounds.
Candace Brown Receives NIH Grant
The National Institutes of Health recently awarded Department of Clinical Pharmacy Professor Candace Brown, MSN, PharmD, BCPP, a grant for more than $2 million over four years for her project
"A Controlled Trial of Gabapentin in Vulvodynia: Biological Correlates of Response."
Provoked vestibulodynia (PVD) is a highly prevalent, chronic pain condition that is costly to the health care system and currently has limited management options available to affected women. The goal of this study is to conduct a multicenter randomized controlled trial of gabapentin treatment for PVD, to define psychophysiologic measures of gabapentin response, and to define mechanistically-based PVD subtypes. This project is a 16-week, randomized, double-blind, placebo-controlled, crossover study that will enroll 120 women between 18 – 50 years of age who report PVD symptoms. Electronically entered daily diaries will be used to determine if pain is lower in PVD subjects when treated with gabapentin (up to 3600 mg/d) compared to treatment with placebo. The long-range goal of the study is to identify underlying pathophysiologic mechanisms of PVD in order to create evidence-based differential diagnoses of subtypes of PVD for more therapeutic and cost-effective management options.