Donald D. Muccio
Professor, Biophysical ChemistryUAB Department of Chemistry
1530 3rd Avenue South
Birmingham AL, 35294-1240
Professor (b. 1950.) obtained his B.S. degree in biophysics at the Ohio State University (1973). Under the direction of Joseph Y. Cassim, he received his Ph.D. degree in molecular biophysics at the Ohio State University (1979) where he used CD spectroscopy to study the membrane protein bacteriorhodopsin. Dr. Muccio was a NIH postdoctoral student in the Department of Chemistry at Case Western Reserve University where he used NMR spectroscopy to study the interactions of retinal with the visual protein rhodopsin. This work was under the direction of Edwin W. Abrahamsom and Gheorghe Matessecu. He joined the Department of Chemistry at UAB in 1982.Research Interests:
A major focus of my research is the design and development of new retinoids for cancer prevention and therapy. We have been successful in developing a highly effective retinoic acid analog, 9cUAB30, that has just finished Phase I human clinical trials. This new UAB retinoid show promise in preclinical studies in preventing breast cancers that are fueled by estrogen (ER+) as well as those that are not (ER-). 9cUAB30 also displays very low toxicity in preclinical studies and human studies, which makes it ideal for long-term administration to patients who wish to prevent cancer recurrence. This compound is currently under investigation for its efficacy in preventing cancer in skin and breast by a team of basic science and clinical investigators.
Using structure-based approaches (X-ray crystallography and NMR), new second and third generation UAB retinoids are being designed, synthesized and studied for their capability to be potent agonists for the retinoid X receptors (see figure for structure of 9cUAB30 bound to RXR). Our laboratory and collaborators also uses an array of computational and biophysical approaches (UV, fluorescence, CD, and ITC as well as mass spectroscopy to study dynamics) to study these retinoid-protein complexes. The biophysical studies will complement detailed in vitro and in vivo studies conducted by our cancer center collaborators.
Kolesar, J.M.; Hoel, R.; Pomplun, M.; Harris, L.; Havighurst, T.; Krontiras, H.; Brouillette, W.; Muccio, D.; Grubbs, C.J.; Bailey, H.E.A Pilot, First in Human, Pharmacokinetic Study of 9cUAB30 in Normal Volunteers, Cancer Prevention Research. 2010, 3 (12), 1-6.
Xia G; Boerma LJ; Cox BD; Qiu C; Kang S; Smith CD; Renfrow MB; Muccio DD. Structure, Energetics, and Dynamics of Binding of Coactivator Peptide to the Human Retinoid X Receptor α Ligand Binding Domain Complex with 9-cis-Retinoic Acid. Biochemistry 2011, 50:93-105.
JM Whitworth, AI Londono-Joshi, JC Sellers, PJ Oliver, DD Muccio, VR Atigadda, JM Straughn, DJ Buchsbaum. The Impact of Novel Retinoids in Combination with Platinum chemotherapy on Ovarian Cancer Stem Cells, Gynecol. Oncol., 2012, Gynecol Oncol 125:226-230.
Vedell, PT; Lu, Y; Grubbs, CJ; Yin, Y; Jiang, H; Bland, KI; Muccio, DD; Cvetkovic, D; You, M; Lubet, R. Effects of Gene Expression in Rat Liver after Administration of RXR Agonists: UAB30, 4-Methyl-UAB30, and Targretin (Bexarotene). Molecular Pharmacol. 2013, 83:698-708.
Cox, BD; Muccio, DD; Hamilton, TP; Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes. Computational and Theoretical Chemistry, 2013, 1011:11-20.
Boerma, LA, Xia, G; Qui, C, Cox, BD, Chamlmers, MJ, Smith CD, Lobo-Ruppert, S, Griffin, P, Muccio, DD, Renfrow, MB. Defining the Communication between Agonist and Coactivator Binding in the Retinoid X Receptor Ligand-binding Domain, J Biol Chem, 2014, 289:814-826.
Desphande, A.; Xia, G.; Boerma, LA.; Vines KK.; Atigadda, VR.; Ruppert, S; Grubbs, CJ.; Moeinpour, FL.; Smith, CD.; Christov, K; Brouillette, WJ.; Muccio, DD Methyl-Substituted Conformationally Constrained Rexinoid Agonists for the Retinoid X Receptors Demonstrate Improved Efficacy for Cancer Therapy and Prevention, Bioorg. Med. Chem. 2014. 22:178-185.
Atigadda, VR; Xia, G.; Deshpande, A.; Boerma, LA.; Lobo-Ruppert, S; Grubbs, CJ.; Smith, CD.; Brouillette, WJ.; Muccio, DD. Methyl Substitution of a Rexinoid Agonist Improves Potency and Reveals Site of Lipid Toxicity. J. Med. Chem. 2014; 57:5370-5380.