Research Program: Tumor Biology and Progression
Professor and Director of Graduate Studies, Department of Medicinal Chemistry

wagne003@umn.edu
612-625-2614 — office

Dr. Wagner received his B.S. degree from the University of North Carolina in 1981 and his Ph.D. from Duke University in 1987. He conducted an NIH-sponsored postdoctoral fellowship in the Department of Chemistry at Pennsylvania State University from 1987-1991.

Research Interests:

Rational design of novel anti-cancer therapeutics and nanotechnology based drug delivery systems by employing, medicinal organic synthesis, immunology protein engineering, biochemistry and molecular modelling; Characterization of arylamine amine carcinogen metabolizing enzymes

The multidisciplinary chemical biological research program pursued in my laboratory applies the areas of synthetic chemistry, medicinal chemistry, enzymology, molecular biology, biochemical pharmacology, X-ray crystallography, electron microscopy, molecular modeling and spectroscopy to; 1) the development of new approaches to drug design and delivery, 2) understanding environmental arylamine carcinogen activation and 3) the engineering of protein nanostructures. My group has been interested in the targeted delivery of antiviral and anticancer nucleotides to virally infected or cancer tissues. Our discovery that bacterial and human Histidine Triad Nucleotide Binding Proteins (Hints) are phosphoramidases, has allowed us to rationally design potential therapeutic nucleotide prodrugs that can be targeted to diseased tissues. We are currently applying our understanding to the design of anticancer and antiviral pronucleotides. In addition, we have discovered a unique and exciting biochemical function for these enzymes, which we are characterizing. In another related project, we are designing unique drug like molecules capable of controlling protein translation in cancer cells. Our hope is that we will be able to use these molecules in combination with known anticancer drugs for the development of more effective chemotherapeutic strategies. Our laboratory is also interested in understanding how arylamine N-acetyltransferases activate common environmental carcinogens. We have developed the first detailed understanding of the catalytic mechanism of these important enzymes and, along with collaborators, are pursuing the structure of these enzymes by NMR spectroscopy. Lastly, because they have a high degree of chemical functionality and structural complexity, proteins could be valuable nanotechnology building blocks. We have begun to develop methods to capture this potential with synthetic chemical dimerizers and designed multimeric proteins. We are applying our new found knowledge to the construction of two and three dimensional nanostructures. Our hope is to use these structures as new scaffolds for the assembly of recombinant antibodies and enzymes.

Visit the Wagner Research Group.

Selected Publications

Chou T-F, Cheng J, Bieganowski P, Brenner C, Wagner CR. 31P NMR and genetic analysis establish hinT as the only E. coli purine nucleoside phosphoramidase and as essential for gGrowth under high salt conditions. J Biol Chem. 2005;280:15356-15361.

Ghosh P, Park J, Peterson M, Bitterman PB, Polunovsky VA, Wagner CR. Design and synthesis of 7-methyl guanosine phosphate analogs as inhibitors of eIF4E. Bioorg Med Chem Lett. 2005; 15:2177-2180.

Wang H, Hanna PE, Wagner CR. The catalyitic mechanism of hamster arylamine N-acetyltransferase 2. Biochemistry 2005;44:11295-11306.

Carlson JTC, Jenna S, Flenniken M, Chou T-F, Siegel R, Wagner CR. Chemically controlled self-assembly of protein nanorings. J Amer Chem Soc. 2006;128:7630-7638.