Research Assistant Professor, Organic Chemistry
M.S., Auburn University, 1992
Ph.D. Auburn University, 1997
The prevention of cancer via chemical agents offers an attractive approach given the recent success of hormonal agents that lower the incidence of breast cancer in high risk individuals. A promising area of study in both the treatment and prevention of cancer is a family of nuclear receptor proteins, which include the retinoic acid receptor (RAR), retinoids X receptor (RXR). Ligands for these receptors have long been known to inhibit tumor growth or formation both in vitro and in vivo. In collaboration with Drs. Donald Muccio and Wayne Brouillette, our laboratory has focused on the design and synthesis of novel retinoids as potential chemoprevention compounds. Some of our retinoids which are conformationally constrained analogues of 9-cis-retinoic acid have exhibited potent breast tumor inhibition in model systems. These rexinoids have shown to selectively bind RXR nuclear receptors and less toxicity in early toxicology as compared to 9-cis retinoic acid. We continue to develop more selective and less toxic retinoids as chemopreventive agents.
The second area of research in my laboratory involves Cystic fibrosis (CF), which is a fatal genetic disease that affects a multitude of exocrine organs, including the airways, pancreas, sweat ducts, reproductive tract, salivary glands, duodenum and liver. The major clinical problem in CF is recurrent lung infections that result in progressive deterioration in lung function. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cAMP-activated chloride channel. The most common CFTR mutation that is known as DF508 is present in at least one allele in 90 percent of CF patients. CFTR with the DF508 mutation lacks a phenylalanine residue at position 508, which impairs the chloride-channel function. In collaboration with Drs. Kevin Kirk and Donald Muccio, our laboratory is actively involved in development of new compounds that correct the defective DF508-CFTR gating.
Efficacy of New Retinoids in the Prevention of Mammary Cancer and Correlations with short-term Biomarkers. Grubbs, C. J.; Lubet, R. A.; Atigadda, V. R.; Christov, K.; Deshpande, A. M.; Tirmal, V.; Xia, G.; Bland, K. I.; Eto, I.; Brouillette, W. J.; Muccio, D. D. Carcinogenesis, 27, 1232-1239, 2006.
Conformationally defined Retinoic Acid Analogous.5. Large-Scale Synthesis and Mammary Cancer Chemopreventive Activity for (2E,4E,6Z,8E)-8-(3’,4’-Dihydro-1’(2’H)-naphthalen-1’-ylidene)-3,7-dimethyl-2,4,6-octatrienoic Acid (9cUAB30). Venkatram R. Atigadda; Vines, K. K., Grubbs, C. J., Hill, D. L., Beenken, S. L., Bland, K., Brouillette, W. J., Muccio, D. D. J. Med. Chem., 46, 3766-3769, 2003.
Efficacy of 9cUAB30, an RXR Specific Retinoid, and/or Tamoxifen in the Prevention of Methylnitrosourea Induced Mammary Cancers. Grubbs, C. J.; Hill, D. L.; Bland, K. I.; Beenken, S. W.; Lin, T-H.; Eto, I.; Atigadda, V. R.; Vines, K.; Brouillette, W. J.; Muccio, D. D. Cancer Letters, 201, 17-24, 2003.