Douglas Covey

Professor of Pharmacology in Developmental Biology, Professor of Psychiatry, Professor of Anesthesiology, Andrew C and Barbara B Taylor Distinguished Professor of Psychiatry

    • 11134 Citations
    1972 …2020

    Research output per year

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    Personal profile

    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 two main areas: neuroactive steroids and oxysterols. Neuroactive steroids affect the functioning of ion-channels involved in synaptic transmission in the central nervous system. Some of these neuroactive steroids are potent anesthetics and others are useful for treatment of several different brain diorders. The chemistry carried out on this project is designed either to provide mechanistic information on how steroids cause their effects in the brain or to provide new structure–activity data for the development of new therapeutic agents. Oxysterols of interest to us are those formed by oxidation of the side chain of cholesterol. We are chiefly interested oxysterol regulation of sonic hedgehog signaling and cholesterol trafficking. We are currently developing click chemistry compounds to identify binding sites for neuroactive steroids and oxysterols on proteins and to allow the imaging of these two classes of steroids and the proteins that bind them in cells.

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    Research Output

    25-Hydroxycholesterol amplifies microglial IL-1β production in an apoE isoform-dependent manner

    Wong, M. Y., Lewis, M., Doherty, J. J., Shi, Y., Cashikar, A. G., Amelianchik, A., Tymchuk, S., Sullivan, P. M., Qian, M., Covey, D. F., Petsko, G. A., Holtzman, D. M., Paul, S. M., Paul, S. M. & Luo, W., Jun 17 2020, In : Journal of Neuroinflammation. 17, 1, 192.

    Research output: Contribution to journalArticle

    Open Access
  • Binding and intracellular transport of 25-hydroxycholesterol by Niemann-Pick C2 protein

    Petersen, D., Reinholdt, P., Szomek, M., Hansen, S. K., Poongavanam, V., Dupont, A., Heegaard, C. W., Krishnan, K., Fujiwara, H., Covey, D. F., Ory, D. S., Kongsted, J. & Wüstner, D., Feb 1 2020, In : Biochimica et Biophysica Acta - Biomembranes. 1862, 2, 183063.

    Research output: Contribution to journalArticle

  • 1 Scopus citations

    Cholesterol Stabilizes TAZ in Hepatocytes to Promote Experimental Non-alcoholic Steatohepatitis

    Wang, X., Cai, B., Yang, X., Sonubi, O. O., Zheng, Z., Ramakrishnan, R., Shi, H., Valenti, L., Pajvani, U. B., Sandhu, J., Infante, R. E., Radhakrishnan, A., Covey, D. F., Guan, K. L., Buck, J., Levin, L. R., Tontonoz, P., Schwabe, R. F. & Tabas, I., May 5 2020, In : Cell metabolism. 31, 5, p. 969-986.e7

    Research output: Contribution to journalArticle

  • 2 Scopus citations

    Neuroactive steroids alphaxalone and CDNC24 are effective hypnotics and potentiators of GABAA currents, but are not neurotoxic to the developing rat brain

    Tesic, V., Joksimovic, S. M., Quillinan, N., Krishnan, K., Covey, D. F., Todorovic, S. M. & Jevtovic-Todorovic, V., May 2020, In : British journal of anaesthesia. 124, 5, p. 603-613 11 p.

    Research output: Contribution to journalArticle

  • 1 Scopus citations

    Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain

    Joksimovic, S. L., Joksimovic, S. M., Manzella, F. M., Asnake, B., Orestes, P., Raol, Y. H., Krishnan, K., Covey, D. F., Jevtovic-Todorovic, V. & Todorovic, S. M., Apr 1 2020, In : British Journal of Pharmacology. 177, 8, p. 1735-1753 19 p.

    Research output: Contribution to journalArticle