Richard Z Lin
Stony Brook University, NY·Pharmacology
Many useful medicines, including some antibiotics, antihistamines and heart-rhythm drugs, have a dangerous side effect: they lengthen the electrical event that drives each heartbeat. This event in each heart muscle cell is called the action potential.
- Fields
Pharmacology
Physiology
Biophysics
- Topics
acquired long QT syndrome
aLQTS
drug-induced arrhythmia
- Grants
- 1 known grant, through Apr 2027
What they work on
- 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.
- Test candidate compounds for their effect on IKs, their dose-response curves and their selectivity, to learn how each binding site controls channel opening.
- Measure how lead compounds change IKs and the action potential in canine ventricular myocytes at several concentrations and pacing rates, with and without a β agonist, including cells with drug-induced lengthening modeling aLQTS.
- Check the safety of lead compounds in canine atrial myocytes (upper-chamber heart cells) to confirm that they do not promote atrial arrhythmias.
More about the research
On an electrocardiogram (EKG), the lengthening shows up as a longer QT interval, a condition called acquired long QT syndrome (aLQTS). aLQTS can trigger a lethal ventricular arrhythmia and sudden death, so these drugs are approved only at limited doses. One way to counter it is to boost IKs, a slowly activating potassium current that helps heart cells reset after each beat and can shorten the action potential.
Why it matters
Patients who need antibiotics, antihistamines or antiarrhythmic drugs face a risk of sudden death from drug-induced long QT syndrome, which forces these drugs to be used at limited doses. Compounds that safely boost the IKs potassium current could prevent this side effect. That could widen the usable dose range of existing drugs and allow promising new drugs that are now held back by this cardiac risk to reach patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
David Auerbach
Upstate Medical University, NY·Physiology
Test whether rabbits with a CRISPR-made Kcnh2 pore mutation reproduce the brain and heart problems of LQT2 patients with epilepsy, including QT prolongation, spontaneous seizures and seizure-related sudden death.
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.
Robert Piper
University of Iowa, IA·Physiology
Produce stably expressing human HEK cell lines that pair individual β subunits (Scn2b, Scn3b, Scn4b) with specific pore-forming NaV α subunits.
The school
Stony Brook University: 32 labs on PI Pages, $319M a year on research, 289 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.