David Auerbach
Upstate Medical University, NY·Physiology
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with epilepsy. Many SUDEP cases carry gene variants linked to heart rhythm disorders, especially long QT syndrome (LQTS), in which the heart takes too long to reset between beats.
- Fields
Physiology
Neuroscience
Pharmacology
- Topics
epilepsy
long QT syndrome
Kv11.1
- Grants
- 1 known grant, through Aug 2027
What they work on
- 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.
- Determine whether heart muscle cells and cortical neurons from Kcnh2 mutant rabbits have reduced IKr, the potassium current made by the Kv11.1 channel, and are electrically hyperexcitable.
- Test with cell assays and live-animal studies whether phenytoin, a sodium channel-blocking seizure drug, blocks IKr and lengthens the QT interval more in Kcnh2 mutant rabbits than in normal rabbits.
More about the research
The PI's team and others have shown that people with long QT syndrome type 2 (LQT2) have more than twice the risk of epilepsy of their relatives without the variant. LQT2 is caused by variants in KCNH2, a gene for the potassium channel Kv11.1. This channel helps heart cells reset after each beat and keeps neurons from firing over and over. These patients need seizure drugs that are safe for their hearts, but no good animal model exists to test such drugs.
Why it matters
People with KCNH2 variants face high risks of epilepsy, SUDEP and dangerous heart rhythms, yet no seizure medications are established as safe for them. Some common seizure drugs may raise their arrhythmia risk. This rabbit model could provide a platform to identify seizure medications that reduce seizures and SUDEP in LQT2 patients without harming the heart.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
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.
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.
Masayuki Yazawa
Icahn School of Medicine at Mount Sinai, NY·Pharmacology
Design, synthesize and characterize new small-molecule Sigma 1 receptor agonists that relieve Timothy syndrome heart cell defects, testing them in human iPSC-derived heart muscle cells and rodent models.
The school
Upstate Medical University: 7 labs on PI Pages, $59M a year on research, 23 research doctorates a year.
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