Dr. W. David Nes
Title: Paul Whitfield Horn Professor
Director, Center for Chemical Biology
Education: Ph.D., University of Maryland, 1979; Postdoctoral Study, NIH Postdoctoral Fellow, University of California, Berkeley; ARS-USDA, Albany, CA
Research Area: Biochemistry and Natural Products
Office: Chemistry 413-C
Principal Research Interests
- Natural Product Chemistry and Metabolomics
- Functional Analysis and Inhibition of Enzymes in Sterol Biosynthesis Pathways
- Mechanistic Enzymology of Sterol Catalysts
The main focus of Professor Nes' research has been to establish the origin, biosynthesis and function of sterols in a range of organisms by unearthing the molecular libraries (genome-metabolome congruence) associated with the phyla-specific reaction sequences that regulate sterol patterning in nature. Particular emphasis is directed at the structure and mechanism of sterol catalysts and the characterization of intracellular metabolite and enzyme specificities involved in sterol production and processing. We have determined the structure of a panoply of naturally occurring isoprenoids and other lipids in stereochemical detail using 1H/13C-NMR/X-ray crystallography and tracked 2H and 13C-labeled intermediates to final products using sensitive labeling techniques. In parallel studies, we have cloned and demonstrated the mechanism and physiological abundance of crucial sterol catalysts in parasites as well as genetically modified sterol biosynthesis in crops.Our research program also involves fruitful collaborations involving several laboratories, including the Waterman/Lepesheva (Nashville, TN), Nguyen (Columbia, MO), Snell (Dallas, TX) and Kelly (Swansea, Wales) laboratories to rationally design and prepare substrate-based inhibitors targeted at 24-alkyl sterol biosynthesis and to examine the factors regulating carbon flux and sterol homeostasis. These studies have led to chemotherapeutic leads to prevent disease by opportunistic parasites dependent on an intact ergosterol pathway and afforded success in engineering transgenic plants with modified sterol seed compositions to benefit human health.
A new graduate student can embark on studies involving natural product isolation and characterization (NMR, GC/MS, HPLC-UV), tracer studies designed to track biosynthesis pathways, prepare and test substrate mimics in vivo against parasites, and learn molecular cloning techniques that involve biochemical applications and molecular biological approaches related to enzyme kinetics, enzyme purification and characterization.