department of developmental biology

Professor

Department of Molecular Biology and Pharmacology
Biochemistry Program
Bioorganic Chemistry Program
Neuroscience Program

Research Interests

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: 1) neuroactive steroids, 2) neuroprotective steroids, 3) cholesterol homeostasis and 4) 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.

Covey Biosketch

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

Positions Held

• 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
• Gilman Fellowship
• Election to Society of the Sigma Xi
• Election to Phi Lambda Upsilon

Selected Publications

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).

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).

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).

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).

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)

Contact Information

Douglas F. Covey
Department of Molecular Biology and Pharmacology
Washington University School of Medicine
Campus Box 8103
660 South Euclid Avenue
St. Louis, MO 63110
(314) 362-1726
dcovey@wustl.edu

The Covey laboratory is physically located in McDonnell Medical Sciences Building, room #355, on the Washington University Medical School campus.