Vasanth Vedantham, MD, PhD

Associate Professor
M_MED-CORE-CARD
Research Overview: 

The heart’s spontaneous rhythmicity has fascinated natural scientists from antiquity to the present. Particularly in the form of the palpable pulse, heart rhythm has always been among the most accessible physiological parameters to physicians, athletes and lay people, and yet the evolution, ontogenesis, and regulation of the heartbeat have remained surprisingly mysterious. In addition to presenting a fascinating biological problem, the origin and regulation of heart rhythm is a pressing public health concern as well, since arrhythmias and slow heartbeat are among the most common forms of heart disease.

Our research explores the biogenesis of heart rhythm in normal and diseased hearts, with particular attention to sinus node dysfunction, cardiac conduction system disease, and atrial fibrillation. Our recent work has focused on the development and function of pacemaker cells in the sinoatrial node, a rare subtype of cardiomyocyte responsible for triggering the heartbeat. We have characterized the transcriptome and chromatin landscape in this critical cell type, and we have identified gene regulatory networks and cis-regulatory elements that are active specifically in pacemaker cells.

Our long-term goals are:

  1. to define the genetic and evolutionary blueprint for vertebrate cardiac rhythmicity by building a comprehensive model for development, function, remodeling, and regenerative potential of specialized conduction tissue, and
  2. to translate this knowledge into new treatments for heart rhythm disorders, including sinus node dysfunction and atrial fibrillation

Specific questions under active investigation include: How are pacemaker cells different from regular heart cells at the level of gene expression and regulation? How does their unique gene expression signature confer their distinctive electrophysiological properties? How have selection pressures generated functional differences in pacemaker cells among different vertebrate species? What are the molecular mechanisms that guide pacemaker cells to integrate electrically with the rest of the heart and with the nervous system to form a node? How do pacemaker cell biology and function change in response to physiological and pathological stress? What is the mechanistic link between sinus node dysfunction and atrial fibrillation? Our approaches include mouse genetics, in-vivo, ex-vivo, cellular, and molecular electrophysiology, imaging, gene expression analysis, genomics, and bioinformatics.

Primary Thematic Area: 
Vascular & Cardiac Biology
Secondary Thematic Area: 
Developmental & Stem Cell Biology
Research Summary: 
Integrative Biology of Heart Rhythm and Mechanisms of Arrhythmias: Development, Physiology, Genetics, Disease, and Regeneration.

Websites

Featured Publications: 

ATAC-seq Reveals an Isl1 Enhancer that Regulates Sinoatrial Node Development and Function.

Circulation research

Galang G, Mandla R, Ruan H, Jung C, Sinha T, Stone NR, Wu RS, Mannion BJ, Allu PK, Chang K, Rammohan A, Shi MB, Pennacchio LA, Black BL, Vedantham V

Premature MicroRNA-1 Expression Causes Hypoplasia of the Cardiac Ventricular Conduction System.

Frontiers in physiology

Samal E, Evangelista M, Galang G, Srivastava D, Zhao Y, Vedantham V

RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.

Circulation research

Vedantham V, Galang G, Evangelista M, Deo RC, Srivastava D