We are interested in the chemistry and biology of steroids. My laboratory specializes in natural products chemistry as it relates to the synthesis of steroids and steroid analogues. The compounds prepared in the laboratory are then studied in laboratories of colleagues throughout the university, and elsewhere, who share with us a common interest in the biological actions of steroids.
Currently our efforts are focused in four main areas:
- Neuroactive steroids
- Neuroprotective steroids
- Cholesterol homeostasis
- Steroid effects on the physical properties of cellular membranes
Neuroactive steroids affect the functioning of ion-channels involved in synaptic transmission in the central nervous systems. Some of these neuroactive steroids are potent anesthetics and the chemistry carried out on this project is designed either to provide mechanistic information on how steroids cause anesthesia or to provide new structure–activity data for the development of new anesthetic steroids.
Neuroprotective steroids are steroids that prevent or reduce neurodegeneration. We are interested in steroids that prevent neuronal cell death caused by oxidative damage.
The complex process whereby cells regulate the production and distribution of cholesterol in cells is incompletely understood. Steroids prepared in this project area are selected for their ability to provide a better understanding of this complex regulation.
Finally, we are interested in understanding the role that cholesterol–sphingomyelin rafts play in cell signaling. We are studying how cell signaling pathways mediated by proteins localized in rafts are altered by changes in the physical properties of their membrane environment.
Keywords: steroid, neurosteroid, neuroprotection, cholesterol, sphingomyelin.
Education and Training
Loyola College, Baltimore, MD B.S. 1967 Chemistry
Johns Hopkins Univ., Baltimore, MD M.A. 1969 Chemistry
Johns Hopkins Univ., Baltimore, MD Ph.D. 1973 Chemistry
Johns Hopkins Univ., Baltimore, MD 73-74 Chemistry
Johns Hopkins Univ., Baltimore, MD 74-77 Pharmacology
1990-present Professor, Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, Missouri
1983-1990 Associate Professor, Department of Pharmacology, Washington University Medical School, St. Louis, Missouri
1977-1983 Assistant Professor, Department of Pharmacology, Washington
University Medical School, St. Louis, Missouri
Honors and Awards
2004 American Chemical Society St. Louis Award
Research Career Development Award
Maryland State Teachers Scholarship
Election to Society of the Sigma Xi
Election to Phi Lambda Upsilon
- Mennerick, S., He, Y., Jiang, X., Manion, B.D., Wang, M., Shute, A., Benz, A., Evers, A.S., Covey, D.F., and Zorumski, C.F. Selective antagonism of 5a-reduced neurosteroid effects at GABAA receptors. Mol. Pharmacol., 65, 1191-1197 (2004).
- Westover, E.J. and Covey, D.F. First synthesis of ent-desmosterol and its conversion to ent-deuterocholesterol. Steroids, 68, 159-166 (2003).
- Jiang, X., Manion, B.D., Benz, A., Rath, N.P., Evers, A.S., Zorumski, C.F., Mennerick, S., and Covey, D.F. Neurosteroid analogues. 9. Conformationally constrained pregnanes: structure–activity studies of 13,24-cyclo-18-21-dinorcholane analogues of the GABA modulatory and anesthetic steroids (3a,5a)- and (3a,5b)-3-hydroxypregnan-20-one. J. Med. Chem., 46, 5334-5348 (2003).
- Tochtrop, G.P., DeKoster, G.T, Cistola, D.P. and Covey, D.F. Synthesis of [3,4-13C]-enriched bile salts as NMR probes of protein–ligand interactions. J. Org. Chem., 67, 6764-6771 (2002).
- Jiang, X. and Covey D.F. The total synthesis of ent-cholesterol via a steroid C,D–ring synthon. J. Org. Chem., 67, 4893-4900 (2002).
- Covey D.F., Evers A.S., Mennerick, S., Zorumski, C.F., and Purdy, R.H. Recent developments in structure–activity relationships for steroid modulators of GABAA receptors. Brain Res. Rev., 37, 91-97 (2001). (Review)