Geoffrey W Abbott
University of California-Irvine, CA·Pharmacology
Potassium channels are pores in cell membranes that open in response to voltage, letting potassium ions flow out. This helps nerve, muscle and heart cells reset their electrical signals.
- Fields
Pharmacology
Physiology
Biophysics
- Topics
ion channels
voltage-gated potassium channels
Kv channels
- Grants
- 2 known grants, through Jul 2030
What they work on
- Delineate how carnosic acid opens Kv7.3 but not Kv7.2, and how gentisic acid potently opens Kv7.3 and Kv7.2/3, using all-atom molecular dynamics simulations, site-directed mutagenesis and electrophysiology.
- Determine how pisiferic acid and gallic acid open Kv1.1 and Kv1.2 channels, simulating whole channels in neuronal membranes, and test whether they rescue a broader panel of ataxia, epilepsy and HSP-linked mutants.
- Test the therapeutic effect and pharmacokinetics of pisiferic acid and gallic acid in mouse models of Episodic Ataxia Type 1 and of Kv1.2-linked ataxia, epilepsy and hereditary spastic paraplegia.
- Dissect how Kv channels and sodium-coupled solute transporters regulate each other in "chansporter" complexes, and discover new channel- and transporter-active molecules from a screen of 1,444 plant extracts.
- Uncover new roles of the potassium channel KCNQ5 in the vasculature and brain using a Kcnq5 knockout rat, and test in vivo the first compounds known to directly rescue EA1-linked Kv1.1 variants.
More about the research
When voltage-gated potassium (Kv) channels of the Kv1 (KCNA) and Kv7 (KCNQ) families fail, the results include epilepsy, ataxia (loss of movement coordination), hereditary spastic paraplegia (HSP, progressive leg stiffness and weakness), addiction, heart rhythm problems and more. Two grants explore how these channels are controlled and how to find small molecules, many from plants, that open them for therapy.
Why it matters
Epilepsy and addiction are major health burdens, and rare disorders such as episodic ataxia and hereditary spastic paraplegia have few treatments. Safe, brain-penetrant plant compounds that open specific potassium channels, together with an understanding of how they work, could become leads for new therapies for ataxia, epilepsy and addiction. Insight into channel-transporter complexes could also inform treatments for pain, inflammation and hypertension.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Christopher A Ahern
University of Iowa, IA·Biophysics
Develop light-activated photochemical 'stapling' to lock voltage-gated sodium, calcium and potassium channels into key shapes in live cell membranes before purification for structural determination.
Naoto Hoshi
University of California-Irvine, CA·Pharmacology
Identify potent compounds that stabilize the binding of Kv7 potassium channels to PIP2, a membrane lipid the channel needs, using a newly developed in silico (computer-based) screening process.
Christina Lee
Carnegie Mellon University, PA·Biochemistry
Determine how the variable C-terminal tails of human atlastins ATL1 and ATL2 block their own membrane fusion activity, including whether the ATL2 tail inserts into the membrane as a helix, using fusion of purified proteins reconstituted in vitro.
The school
University of California-Irvine: 46 labs on PI Pages, $645M a year on research, 524 research doctorates a year.
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