Douglas F. Covey

Mycobacterium tuberculosis inactivates host oxysterols to impair macrophage cholesterol homeostasis

This study identifies Mtb's enzymatic inactivation of host oxysterols as a mechanism to disrupt macrophage cholesterol homeostasis and generate treatment-responsive metabolic signatures in TB.

Regulation of the human voltage-gated proton channel by membrane sterols

This study investigates how cholesterol and its analogs regulate the hHv1 proton channel by altering S4 segment conformation, identifying key residues and mechanisms involved.

Host-derived lipids license proliferation of sterol-auxotrophic tick cells and promote flavivirus output

This study shows host-derived lipids are essential for tick cell proliferation and flavivirus output, revealing their role in regulating cellular state and viral production.

Subunit selective modulation of GABAA receptors using pharmacogenetically tethered neurosteroids

The paper develops a DART platform to selectively modulate GABAA receptor subunits using neurosteroids, identifying C11-linked compounds that enhance GABA currents in 4/{delta}-containing receptors.

A Non-Classical Neuroactive Steroid Exhibiting Potent, Efficacious GABA A Receptor Agonism and NMDA Receptor Inhibition

This paper characterizes YX84, a novel neuroactive steroid with dual GABA A receptor agonism and NMDA receptor inhibition, showing favorable behavioral tolerability.

Live-cell imaging and lipidomics of low density lipoprotein containing intrinsically fluorescent cholesteryl esters

This study uses live-cell imaging and lipidomics to track LDL-derived cholesteryl esters in cells, revealing their transport and metabolism kinetics.

The orientation of cholesterol's hydroxyl group affects its membrane dynamics and intracellular transport

This study shows that the orientation of cholesterol's hydroxyl group affects membrane dynamics and intracellular transport in human astrocytes.

VDAC activation inhibits hippocampal plasticity via NLRP3 inflammasome & caspase-1: modulation by allopregnanolone enantiomers

This study shows that VDAC activation by erastin inhibits hippocampal long-term potentiation and memory formation, effects that are prevented by allopregnanolone and its enantiomer.

Target validation uncouples TSPO from 19-Atriol-mediated inhibition of steroidogenesis and reveals true enzymatic targets

This study shows 19-Atriol inhibits steroidogenesis by directly targeting 3β-HSD and other enzymes, not via TSPO, resolving a long-standing mechanistic confusion.

Phosphorylation of CRYAB Induces a Condensatopathy to Worsen Post-Myocardial Infarction Left Ventricular Remodeling.

This study shows that phosphorylation of CRYAB leads to condensate formation and worsens heart failure after myocardial infarction.

Multifaceted Actions of Neurosteroids

The paper investigates the range of actions of neurosteroid analogues using in silico and in vitro methods, revealing unexpected modulation of multiple targets beyond GABA-A receptors.

Facilitation of Cav3.2 channel gating in pain pathways reveals a novel mechanism of serum-induced hyperalgesia

The paper identifies a novel mechanism of serum-induced hyperalgesia through the facilitation of Cav3.2 channel gating by the peptide albumin (1-26).

Endogenous and fluorescent sterols reveal the molecular basis for ligand selectivity of human sterol transporters

The paper profiles fluorescent steroid probes across ten STPs to uncover selectivity differences and establishes a screening panel to identify new Aster-B inhibitors.

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

This study shows that 25-HC enhances IL-1β production in microglia, particularly in apoE4-expressing cells, suggesting a role in AD neuroinflammation.

Multiple Functional Neurosteroid Binding Sites on GABAA Receptors

The paper identifies three distinct neurosteroid binding sites on the human 1β3 GABAA receptor using photolabeling and computational methods, showing their functional importance in neurosteroid action.