Alex Evers
Washington University in St Louis, MO·Pharmacology
Steroid molecules made in the brain, called neurosteroids, and cholesterol can change how proteins embedded in cell membranes work. Neurosteroids control how excitable nerve cells are and shape nervous system development.
- Fields
Pharmacology
Biophysics
Neuroscience
- Topics
neurosteroids
cholesterol
GABAA receptor
- Grants
- 1 known grant, through May 2028
What they work on
- Map the exact binding sites of major neurosteroid classes on common synaptic and extrasynaptic GABAA receptors, using photolabeling and middle-down and intact protein mass spectrometry.
- Test the function of each neurosteroid binding site by changing single amino acids and measuring how neurosteroids alter GABAA receptor currents.
- Obtain high-resolution cryo-EM structures showing the atomic details of new neurosteroid binding sites and receptor shapes that these steroids may stabilize.
- Measure site-specific neurosteroid affinity and state-dependent binding with fluorescence assays and stopped-flow fluorimetry, and adapt them to plate-reader screens for site-specific agonists and antagonists.
- Determine the role of two cholesterol binding sites on the lipid scramblase nhTMEM16 and the lysosomal protein GPR155, using amino acid substitutions and new fluorescence binding assays.
More about the research
They also have strong potential as anesthetics, antidepressants and brain-protective drugs. To design better drugs, researchers need to know exactly where these sterols attach to their target proteins and what each attachment site does.
Why it matters
Neurosteroids have potential as anesthetics, antidepressants and neuroprotective drugs. Mapping where they bind GABAA receptors could lead to site-specific compounds that act on particular receptor types. Newly identified cholesterol binding sites offer targets for small molecules that tune membrane protein function. The tools developed could be applied to other cholesterol-regulated proteins.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Edward Twomey
Johns Hopkins University, MD·Biophysics
Determine how AMPA receptors, glutamate-activated channels that carry fast signals between neurons, open and close on a millisecond timescale, using time-resolved cryo-electron microscopy that captures rapid structural snapshots.
Lan Zhu
Medical College of Wisconsin, WI·Biophysics
Determine the structures of non-Class B GPCRs bound to receptor activity-modifying proteins (RAMPs) using cryo-EM, crystallography, and molecular dynamics, to learn how RAMPs control surface localization and ligand recognition.
Show-Ling Shyng
Oregon Health & Science University, OR·Biophysics
Solve cryo-EM structures of pancreatic, cardiac and vascular KATP channels in closed and open states, to build a complete set showing how the channels open in response to ATP and ADP.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.