Steven Marx

What they work on

1. 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.
2. Map the upstream and downstream pathways that modulate adrenergic control of CaV1.2 in healthy and failing hearts, using proximity labeling and quantitative proteomics to track proteins in the channel's immediate neighborhood.
3. Test the role of Rad in human heart disease by analyzing common and rare RRAD variants in ~20,000 heart-failure and ~45,000 myocardial-infarction cases with matched controls, and phenotyping mutation carriers in consanguineous Pakistan Genome Resource families.
4. Test whether AAV9-delivered gene and base editing of Rad or of the calcium-channel beta-subunit slows functional decline in non-ischemic mouse heart-failure models and restores function after failure has begun.
5. Ask whether limiting the sympathetic boost of calcium influx eases cardiac dysfunction in mouse models of catecholaminergic polymorphic ventricular tachycardia and hypertrophic cardiomyopathy.
6. Determine whether blocking catecholamine-driven calcium influx reduces arrhythmia generation and protects against stress-induced cardiomyopathy, and how aging alters adrenergic regulation of calcium handling and contractility.
7. Test whether phosphorylation of Rad and/or of the calcium-release channel RyR2 is required for adrenergic-agonist-induced atrial fibrillation, using the corresponding phosphorylation-site knock-in mice.
8. Define the protein neighborhoods of the sodium channel NaV1.5, CaV1.2, and RyR2 in atrial heart cells using proximity labeling, and determine how they change in heart failure, a condition that predisposes to atrial fibrillation.
9. Identify which cysteine residues of atrial RyR2 are oxidized in mice and humans with atrial fibrillation, and assess their structural effects using a cryo-EM structure of human recombinant RyR2 and electrophysiology on mutant channels.

More about the research

Why it matters

Heart failure and arrhythmias are leading causes of death, and current drugs that push the heart harder must be given intravenously with close monitoring because they can trigger lethal rhythms. By pinpointing Rad as the molecular switch for adrenergic control of cardiac calcium channels, this work could identify a way to strengthen contraction without the calcium overload and leak caused by existing agents, and could point to treatments for inherited arrhythmia syndromes and for atrial fibrillation, which affects roughly 6% of Americans over 65 and recurs often after drugs or ablation.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Closest labs

The school

Columbia University: 89 labs on PI Pages, $1.4B a year on research, 625 research doctorates a year.

More about Columbia University

Reach out

A start for your email. Fill in the brackets.