Faculty

Resistance of pathogenic bacteria to the current armamentarium of antibiotics remains a major roadblock to the desired clinical resolution of many infections. As important bacterial pathogens become increasingly resistant, the lack of new or alternative antimicrobial agents makes serious outbreaks a possibility. There is an urgent need to develop novel antibiotics directed towards newer sites of action.

Presently, research in our lab focuses on the design of novel antimicrobial chemotherapeutics directed against essential biochemical pathways in pathogenic microorganisms. Emphasis is primarily focused on generating "lead compounds," molecules having the desired inhibitory action on the target of interest, based either on a detailed understanding of enzyme mechanism and/or high throughput screening of compound (peptide and non-peptide) libraries using various molecular genetic techniques. In an iterative fashion, information obtained from studies on the inhibitory properties of the lead compounds will be used to design subsequent generations of inhibitors with more optimal properties. Targets of interest include enzymes involved in bacterial coenzyme A and lipopolysaccharide biosynthesis.

Awards

EPA Presidential Green Chemistry Challenge Award (DuPont)
DuPont Work/Life Award
NIH Pharmacological Sciences Training Grant
American Foundation for Pharmaceutical Education Fellow
William C. Sunkins Memorial Award

Representative Publications

1. Liao, D.I., Reiss, L., Turner, I. and Dotson, G.D., "Structure of glycerol dehydratase reactivase. A new type of molecular chaperone", Structure, 2003, 11(1), 109.

2. Liao, D.I., Dotson, G.D., Turner, I., Reiss, L. and Emptage, M., "Crystal structure of substrate free form of glycerol dehydratase", J. Inorg. Biochem., 2003, 93(1-2), 84.

3. Wyckoff, T.J.O., Lin, S., Cotter, R.J., Dotson, G.D. and Raetz, C.R.H., "Hydrocarbon rulers in UDP-N-acetylglucosamine acyltransferases", J. Biol. Chem., 1998, 273(49), 32369.

4. Dotson, G.D. and Raetz, C.R.H., "Expression cloning of a Pseudomonas gene encoding a hydroxydecanoyl-acyl carrier protein-dependent UDP-GlcNAc acyltransferase", J. Bacteriol., 1998, 180(2), 330.

5. Dotson, G.D., Dua, R.K., Clemens, J.C., Wooten, E.W. and Woodard, R.W., "Overproduction and One-Step Purification of Escherichia coli 3-Deoxy-d-manno-octulosonic acid-8-phosphate Synthase and Oxygen Transfer Studies during Catalysis using Isotopic-shifted Heteronuclear NMR", J. Biol. Chem., 1995, 270, 13698.