Naoto Hoshi
University of California-Irvine, CA·Pharmacology
Chronic pain affects about 50 million adults in the US, and safer non-opioid treatments are needed. One cause of pain is that nerve cells become too easy to fire.
- Fields
Pharmacology
Neuroscience
Physiology
- Topics
Kv7 channels
M-current
potassium channels
- Grants
- 1 known grant, through Jul 2027
What they work on
- 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.
- Verify candidate compounds with electrophysiology, testing whether they prevent receptor-induced suppression of the Kv7.2/M-current and shift the voltage at which the channel activates.
- Pinpoint the channel–drug interactions behind the compounds' effects by combining mutation analysis of Kv7 channels with computational simulation.
- Evaluate whether the new Kv7 modulators reduce pain responses in mice, and whether they cause sedation.
More about the research
Normally, potassium channels called Kv7 act as a brake. They carry a current, the M-current, that keeps neurons from firing at rest. Some inflammatory signals and neurotransmitters switch this brake off for a while, which makes neurons more excitable and pain worse. Keeping the brake on could be a new way to ease sensitized pain.
Why it matters
Many people live with chronic pain, and current options often rely on opioids. Compounds that keep Kv7 channels working during inflammation could become the basis for a new class of non-opioid pain drugs. The work could also show how to get past the limits of existing Kv7 channel openers, and would give drug developers a new binding site to target.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Crystal Archer
University of Arkansas, AR·Biophysics·Early-career
Solve the solution structure of the purified Kv7.2 C-terminal region, the channel's internal tail where helper molecules bind, using advanced 3D and 4D NMR spectroscopy.
Kevin Tidgewell
University of Kentucky, KY·Pharmacology
Isolate bioactive compounds from Cameroonian medicinal plants such as Paullinia pinnata by fractionating extracts and testing each fraction for binding to sigma-2/TMEM97, a calcium-regulating protein linked to pain.
Richard Z Lin
Stony Brook University, NY·Pharmacology
Identify compounds that increase the IKs potassium current by acting on its calmodulin and ATP interactions or on pore opening, using structure-based computer screening of a library of more than one million compounds.
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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