Martin Morad
University of South Carolina-Columbia, SC·Physiology
A heartbeat begins with a pulse of calcium. Inside each heart muscle cell, calcium is stored in an internal reservoir, the sarcoplasmic reticulum, and released through a large channel protein called the ryanodine receptor type 2, or RyR2.
- Fields
Physiology
Medicine & Clinical Research
Biophysics
- Topics
ryanodine receptor
RyR2
calcium signaling
- Grants
- 1 known grant, through Jul 2027
What they work on
- Compare calcium-signaling defects caused by CPVT1 mutations in different regulatory regions of the cardiac calcium-release channel RyR2 in maturated human iPSC-derived heart cells, reverse them by editing the sequence back, and test drug responses.
- Determine how mutating the calcium- and caffeine-binding sites of RyR2, predicted from near-atomic structures, changes channel regulation and whether the two sites influence one another.
- Characterize CPVT1 mutations that reduce RyR2 function and identify what distinguishes calcium-leaky from non-leaky variants, using patch-clamp recordings with confocal and TIRF calcium imaging.
- Validate the human stem-cell platform by comparing calcium abnormalities in edited iPSC-derived cardiomyocytes with mice carrying knock-in versions of the same RyR2 mutations, and by [3H]ryanodine binding assays of ligand affinity.
More about the research
If that channel leaks calcium at the wrong moment, the heart can beat chaotically. Mutations in RyR2 cause catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1), an inherited rhythm disorder in which exercise or stress triggers dangerous arrhythmias in otherwise healthy young people. This project asks, in human heart cells, how specific CPVT1 mutations change the way RyR2 is controlled by calcium itself, by caffeine, and by the accessory protein FKBP12.6.
Why it matters
Faulty calcium release through RyR2 contributes to inherited arrhythmias such as CPVT1 and also to heart failure. Linking individual mutations to measurable calcium defects in human heart cells, and testing which drugs rescue which mutation, could support mutation-specific treatment choices for affected families and give a human testbed for candidate antiarrhythmic compounds that is closer to the patient than mouse or kidney-cell models.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Dmitry A Terentyev
Ohio State University, OH·Physiology
Test whether overactive RyR2, the heart's calcium-release channel, activates calpain, a calcium-activated enzyme inside mitochondria, which then breaks down OPA1, a protein that shapes mitochondrial inner folds, using a rat model of CPVT the lab created.
Steven Marx
Columbia University, NY·Physiology
Determine how β-adrenergic stimulation of the CaV1.2 calcium channel changes in heart failure, using knock-in mice whose Rad brake protein cannot be phosphorylated by protein kinase A and mice lacking the Rad–beta-subunit interaction.
Shey-Shing Sheu
Thomas Jefferson University, PA·Physiology
Test whether hypertrophic stress raises levels of mitochondrial ryanodine receptor type 1 (mRyR1), a calcium channel, to boost mitochondrial calcium uptake and ATP production, using RyR1-overexpressing and other mouse models.
The school
University of South Carolina-Columbia: 22 labs on PI Pages, $277M a year on research, 425 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.