个人简介

Ph.D., University of Maryland, 1979; Postdoctoral Study, NIH Postdoctoral Fellow, University of California, Berkeley; ARS-USDA, Albany, CA

研究领域

Biochemistry and Natural Products

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.

近期论文

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"Novel Sterol Metabolic Network of Trypanosoma brucei Procyclic and Bloodstream Forms." Nes, C. R.; Singha, U. K.; Liu, ,J.; Villalta, F.; Waterman, M. R.; Lepesheva, G. I.; Chaudhuri, M. and Nes, W. D. Biochem. J. 2012, 443, 267-276. "Evolutionarily Conserved ∆25(27)-Ergosterol Biosynthesis Pathway in the Alga Chlamydomonas reinhardtii is Distinct from the ∆24(28)-Pathway to Fungal Ergosterol." Miller, M. B.; Haubrich, B. A.; Wang, Q.; Snell, W. J. and Nes, W. D. J. Lipid Res. 2012, 53, 1636-1645. "Sterol C24-Methyltransferase: Physio- and Stereochemical Features of the Sterol C3-Group Required for Catalytic Competence." Howard, A. L.; Jiu, J.; Elmegeed, G. A.; Collins, E. K.; Gantra, K. S.; Nwogwugwu, C. A. and Nes, W. D. Arch. Biochem. Biophys. 2012, 521, 43-50. "Metabolic Engineering of Soybean Affords Improved Phytosterol Seed Traits." Neelakanda, A.; Valliyodan, B.; Chamala, S.; Nes, W. D. and Ngueyn, H. T. Plant Biotech. J. 2012, 10, 12-19. "Structural Complex of Sterol 14α-Methyldemethylase (CYP51) with 14α-Methylenecyclopropyl -∆7-24,25-Dihydrolanosterol." Hargrove, T. Y.; Wawrzak, Z.; Liu, J.; Waterman, M.R.; Nes, W. D. and Lepesheva, G. I. J. Lipid Res. 2012, 53, 311-320. "Unearthing the Biosynthetic Diversity in the Sterol Metabolome." Nes, W. D. Pharmaceutical Biol. 2012, 50, 633-633. "Biosynthesis of Cholesterol and Other Sterols." Nes, W. D. Chem. Rev. 2011, 111, 6423-6451. "Mechanism of Binding of Prothioconazole to Mycosphaerella graminicola CYP51 Differs from that of Other Azole Antifungals." Parker, J. E.; Warrilow, A. G. S.; Cools, H. J.; Martel, C. M.; Nes, W. D.; Fraije, A.; Lucas, J. A.; Kelly, D. A. and Kelly. S. L, Appl. Environ. Microbiol. 2011, 77, 1460-1465. "Purification, Characterization, and Inhibition of Sterol C24-Methyltransferase from Candida albicans." Ganapathy, K.; Kanagasabai, R.; Nguyen, T. T. M. and Nes, W. D. Arch. Biochem. Biophys. 2011, 505, 194-201. "Substrate Preferences and Catalytic Parameters Determined by Structural Characteristics of Sterol 14α-Demethylase CYP51 from Leishmania infantum." Hargrove, T. Y.; Liu, J.; Nes, W. D.; Waterman, M. R. and Lepesheva. G. I. J. Biol. Chem. 2011, 286, 26838-26848. "Effect of Substrate Features and Mutagenesis of Active Site Tyrosine Residues on the Reaction Course Catalyzed by Trypanosoma brucei Sterol C24-Methyltransferase." Liu, J.; Ganapathy, K.; Wywial, E.; Bujnicki, J. M.; Nwogwugwu, C. A. and Nes, W. D. Biochem. J. 2011, 439, 413-422.