Donald Muccio. Professor Emeritus


Research Interests: Design and Structural Studies of Rexinoids with Retinoid X Receptors, Development of Drugs for Cancer Chemoprevention & Therapy, Development of Drugs for Treatment of Obesity, Diabetes and Lipidemia, Structure, Dynamics and Stability of Ligand-Receptor Complexes

Teaching Interests:  Metabolic Biochemistry, Protein Structure and Physical Biochemistry Methods

Office Hours: By appointment

  • BA, The Ohio State University, Biophysics
  • PhD, The Ohio State University, Molecular Biophysics
  • NIH-Funded Postdoctoral, Case Western Reserve University, Chemistry

I was raised in a small town in northeast Ohio. My parents were either first or second generation Italian-Americans. We had an extended family where my aunts and uncles were like parents, and my cousins were my sisters and brothers. Our motto was family, food, and fun. My parents were never formally educated but they valued it greatly. They instilled a sense of hard work that only a middleclass immigrant family can, while we played and watched sports. My brothers and I worked hard and when we went to college we were expected to get a solid education. I still carry these principles with me today; work hard and have fun doing so.

Our research efforts center on vitamin A and its metabolites, since they are essential skin cells maturation and development. My laboratory is involved with the design of new retinoids that are effective drugs to prevent/treat disease without toxicity. More specifically, my research group designs, syntheses and studies how our UAB retinoids bind to the retinoid X receptors (RXRs) and act as agonist in important signaling pathways. We have used structural biological studies (x-ray diffraction; quantum mechanical and molecular dynamic computational methods), thermodynamic approaches (ITC; DSC), and recently hydrogen-deuterium exchange mass spectrometer (HDX MS) to understand the molecular interactions between retinoids and RXRs.

Our group is most well-known for the design and translational development of UAB30, a Class II UAB rexinoid. UAB30 is now in human clinical trials that are evaluating it for toxicity, pharmacology, and its efficacy as a new drug for cancer prevention. UAB30 is being carefully evaluated by the NCI and UAB clinicians, since it does not cause toxicity associated with other clinically used retinoids. UAB30 does not cause lipid toxicity or have other unfavorable effects on metabolism, yet it is efficacious in preventing cancer derived from epithelial tissues.
I teach a variety of biochemistry courses ranging from metabolic biochemistry (CH460) to protein structure and physical biochemistry methods (CH461/464). I also teach introductory graduate courses on physical biochemistry emphasizing the understanding of the thermodynamics small molecule binding and recognition to macromolecules (CH700).
  • CH 460/461/464
  • CH 700 (team taught)
  • Xia, G.; Boerma, L. J.; Cox, B. D.; Qiu, C.; Kang, S.; Smith, C. D.; Renfrow, M. B.; Muccio, D. D. 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.
  • Whitworth, J. M.; Londono-Joshi, A. I.; Sellers, J. C.; Oliver, P. J.; Muccio, D. D.; Atigadda, V. R.; Straughn, J. M.; Buchsbaum, D. J. The Impact of Novel Retinoids in Combination with Platinum chemotherapy on Ovarian Cancer Stem Cells. Gynecol. Oncol. 2012, 125, 226-230.
  • Vedell, P. T.; Lu, Y.; Grubbs, C. J.; Yin, Y.; Jiang, H.; Bland, K. I.; Muccio, D. D.; 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, B. D.; Muccio, D. D.; Hamilton, T. P.; Conformational Analysis of Retinoic Acids: Effects of Steric Interactions on Nonplanar Conjugated Polyenes. Computational and Theoretical Chemistry, 2013, 1011, 11-20.
  • Boerma, L. J.; Xia, G.; Qui, C .; Cox, B. D.; Chalmers, M. J.; Smith, C. D.; Lobo-Ruppert, S.; Griffin, P.; Muccio, D. D.; Renfrow, M. B. Structural Analysis of Clinically Relevant Agonists of Retinoid X Receptors. J Biol. Chemistry, 2014, 289, 814-826.
  • Desphande, A.; Xia, G.; Boerma, L. A.; Vines, K.K.; Atigadda, V.R.; Ruppert, S.; Grubbs, C. J.; Moeinpour, F. L.; Smith, C. D.; Christov, K.; Brouillette, W. J.; Muccio, D. D. 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, V.R; Xia, G.; Deshpande, A.; Boerma, L. A.; Lobo-Ruppert, S.; Grubbs, C. J.; Smith, C. D.; Brouillette, W. J.; Muccio, D. D. Methyl Substitution of a Rexinoid Agonist Improves Potency and Reveals Site of Lipid Toxicity. J. Med. Chem. 2014, 57, 5370-5380.
  • Vedell, P. T.; Townsend, R. R.; You, M.; Malone, J.; Grubbs, C. J.; Bland, K. I.; Muccio, D. D.; Atigadda, V. R.; Chen, Y.; Vignola, K.; Lubet, R. A. Global molecular changes in rat livers treated with RXR agonists: a comparison using transcriptomics and proteomics. Pharmacology Research & Perspectives, 2014, 2, 1-16.
  • Waters, A. M.; Stewart, J. E.; Atigadda, V. R.; Muccio, D. D.; Grubbs, C. J.; Beierle, E. Pre-Clinical Evaluation of a Novel RXR Agonist for the Treatment of Neuroblastoma, Molecular Cancer Therapeutics, 2015, 14, 1559-1569.
  • Atigadda, V. R.; Xia, G.; Deshpande, A.; Wu, L.; Kedishvili, N.; Smith, C. D.; Krontiras, H.; Bland, K. J.; Grubbs, C. J.; Brouillette, W. J.; Muccio, D. D. Conformationally Defined Rexinoids and Their Efficacy in the Prevention of Mammary Cancer. J. Med. Chem. 2015; August 20 issue; in press.
  • Muccio, D. D.; Brouillette, W. J.; Atigadda, V. R.; Grubbs, C. J.; Krontiras, H. Translation of a Tissue-Selective Rexinoid to the Clinic for Breast Cancer Prevention. Current Topics in Medicinal Chemistry; 2015. Invited review on ‘Rexinoids’ to be published in the December 18, 2015 issue of Current Topics Medicinal Chemistry; editor for special edition: Carl Wagner, Arizona State University.

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