Douglas F. Covey
Medicinal chemist and Andrew C and Barbara B Taylor Distinguished Professor of Psychiatry at Washington University in St. Louis who designs synthetic steroids and sterols to study neurosteroids, GABA-A receptors and cholesterol sensing, including in two Atlas studies on cholesterol and mTORC1
Andrew C and Barbara B Taylor Distinguished Professor of Psychiatry · Professor of Developmental Biology, of Anesthesiology and of Psychiatry, Washington University School of Medicine, St. Louis · Taylor Family Institute for Innovative Psychiatric Research
Portrait: Department of Developmental Biology, Washington University School of Medicine
Douglas Covey is a co-author of two Atlas studies from the Zoncu lab on how lysosomes tell mTORC1, the growth-control complex, that cholesterol is available. In CAS2017 the team showed that cholesterol in the lysosome membrane switches on mTORC1. The transporter SLC38A9 is needed for this through cholesterol-responsive parts of the protein, separate from its role in sensing arginine, while NPC1, the protein that exports cholesterol out of the lysosome, binds SLC38A9 and holds mTORC1 back. In SHI2022 they found a second sensor, LYCHOS (formerly called GPR155). When cholesterol is high, LYCHOS binds GATOR1, a brake on mTORC1, and takes it out of action, so mTORC1 can be recruited to the lysosome. Both studies were done mainly in cultured cells.
Covey's own field is the chemistry of steroids and sterols. Covey's group at Washington University makes modified versions of these molecules and tests how small changes in shape alter what they do. Much of this work, often with Mennerick, concerns neurosteroids, natural brain steroids that act on GABA-A receptors, the main inhibitory receptors of the brain, and their potential for treating psychiatric disorders. Recent papers use machine learning and screening to find new neurosteroid targets (2025), test steroid and sterol analogues on inflammation in brain immune cells (2026) and show that flipping the orientation of one hydroxy group in cholesterol changes how the molecule moves inside cells (2026).
Covey holds the Andrew C and Barbara B Taylor Distinguished Professorship of Psychiatry at Washington University School of Medicine, together with professorships in developmental biology, anesthesiology and psychiatry. PubMed also lists the Taylor Family Institute for Innovative Psychiatric Research. In September 2026 the Department of Developmental Biology held a half-day symposium named after Covey.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2017 | M | Lysosomal cholesterol activates mTORC1 via an SLC38A9-Niemann-Pick C1 signaling complex CAS2017 Co-author: lysosomal cholesterol activates mTORC1 through SLC38A9, and NPC1 restrains this signal. |
| 2022 | M | Lysosomal GPCR-like protein LYCHOS signals cholesterol sufficiency to mTORC1 SHI2022 Co-author: identified LYCHOS as a lysosomal cholesterol sensor that releases mTORC1 by binding GATOR1. |
Co-authors in the Atlas 8
People with a profile here who share at least one study with Douglas F. Covey.
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- Daniel K. Nomura 2 shared studies Chemical biologist and professor at UC Berkeley who uses chemoproteomics to find druggable sites on proteins, including covalent handles that turn ordinary drug molecules into protein degraders
- Oliver B. Davis 2 shared studies Cell biologist who did a PhD in Roberto Zoncu's lab at UC Berkeley on how lysosomal cholesterol controls mTORC1, and first author of a 2020 study proposing NPC1-mTORC1 signalling as a drug target in Niemann-Pick type C disease
- Rushika M. Perera 2 shared studies Professor of Anatomy at UCSF whose lab studies how autophagy and the lysosome, the cell's recycling centre, help cancer cells cope with stress, and a co-author of two Science papers on how lysosomal cholesterol switches on mTORC1
- Ashley M. Thelen Cell biologist who did graduate work in Roberto Zoncu's lysosome lab at UC Berkeley, first author of a 2017 review on the lysosome's roles in lipid metabolism, and later a postdoctoral scholar in Philip Greenberg's lab at Fred Hutch
- Brian M. Castellano Cell biologist who, in Roberto Zoncu's lab at UC Berkeley, showed that cholesterol inside the lysosome switches on mTORC1 through the SLC38A9 and NPC1 proteins
- Hijai R. Shin Cell biologist who discovered, in Roberto Zoncu's lab at UC Berkeley, that the lysosomal protein LYCHOS senses cholesterol for mTORC1, and who now works at the Children's Medical Center Research Institute at UT Southwestern
- Chun-Yan Lim Cell biologist who trained in Roberto Zoncu's lab at UC Berkeley on how cholesterol controls mTORC1, and now publishes as corresponding author from Guangzhou National Laboratory on lysosome signalling in immunity and nutrient sensing
- Ofer Moldavski Researcher who worked on lysosomes and lipid signalling in Roberto Zoncu's lab at UC Berkeley and was first author of a 2021 study on how the oxysterol 4beta-hydroxycholesterol switches on fat-making genes
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