Integrative Biology of Heart Rhythm and Mechanisms of Arrhythmias: Development, Physiology, Genetics, Disease, and Regeneration
Vasanth Vedantham, Professor
UC San Francisco
Closed. This professor is continuing with Fall 2024 apprentices on this project; no new apprentices needed for Spring 2025.
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 initiating 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
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, stem cell culture with human iPSCs, imaging, gene expression analysis, genomics, and bioinformatics.
Role: Specific tasks to be assigned will depend on the interest and skill level of the undergraduate but could include the following: basic molecular biology (PCR, cloning), histological analysis of heart tissue (cutting and staining of heart tissue), experiments with mouse models including assisting with electrocardiogram data acquisition and analysis, isolation of heart cells, imaging of hearts using microscopy, and assistance with human pluripotent stem cell culture.
Specific learning outcomes for Spring 2023 will be: (1) the student will learn to design and perform one or two types of laboratory experiments, and to analyze the data rigorously; (2) the student will develop topic-area knowledge about heart rhythm; (3) the student will have the opportunity to present their work to a group of scientists.
Our lab has worked with 5 URAP students previously, all of whom have been co-authors on published work or soon-to-be-published work. After working with us, URAP students have successfully applied to medical school and taken positions in academic labs and graduate school. Therefore, for students interested in a longitudinal experience, there are opportunities to continue research through the summer and over more than 1 year in the lab which often can result in broader and more independent research projects.
Qualifications: Prior experience working with mice, prior cell culture experience, prior cardiovascular research experience, or prior computational/bioinformatics experience would be ideal, but any molecular biology lab experience coupled with a strong interest in our research questions would be acceptable.
Hours: 9-11 hrs
Off-Campus Research Site: University of California, San Francisco Smith Cardiovascular Research Building 555 Mission Bay Blvd San Francisco, CA 94158
Related website: https://vedantham.ucsf.edu