Todd J. Herron, Ph.D., Assistant Research Professor
Molecular & Integrative Physiology
Center for Arrhythmia Research
University of Michigan-Molecular and Integrative Physiology, Individual NRSA Research Fellow (2006-2007)
University of Michigan-Cardiology, NRSA Training Grant Fellow (2004-2006)
Kings College London-Cardiology, Postdoctoral Fellow (2002-2004)
University of Missouri-Ph.D., Department of Physiology (1997-2002)
Each heart beat involves the complex interplay between electrical excitation of cardiac muscle and subsequent contraction and muscle shortening. This process is classically known as excitation-contraction coupling. The excitation-contraction coupling process is highly regulated in the normal healthy heart and dysregulation of this process contributes to the pathogenesis of heart disease. For example, heart disease can be caused by inherited mutations of genes that encode proteins responsible for the contraction process: the sarcomere proteins. Mutations of the sarcomere proteins can cause disturbances in the electrical excitation of cardiac muscle and can predispose affected patients to fatal arrhythmias and sudden death. The link between mutated sarcomere proteins and fatal arrhythmias is unclear. One aspect of research in the lab is focused on mechanisms whereby a mutant contractile protein can predispose the heart to the development of fatal arrhythmias.
Disease causing mutations of cardiac myosin. We have generated adenoviruses to express disease causing myosin mutants in cardiac myocytes in vitro. These mutant myosin molecules cause ventricular arrhythmias and sudden death in competitive athletes. Experiments are planned to test the effects of these mutant myosins on myocyte force development, calcium homeostasis and electrophysiology.
Myosin isoform switching in heart failure. Heart failure is associated with exclusive expression of a slow myosin motor in the heart and loss of fast myosin motor expression. We have developed a rabbit model of heart failure and are testing the effectiveness of fast myosin motor gene transfer to increase myocyte and whole heart contractile function. The effectiveness of RNA silencing to turn off the slow myosin motor expression is also being explored.
Calcium homeostasis in a mouse model of catecholaminergic polymorphic ventricular tachycardia. This project is a collaborative effort with Dr. Jalife's laboratory. Using a knock-in transgenic mouse model that expresses a mutant ryanodine receptor (R4496C), Dr. Jalife's lab has identified the His-Purkinje system as the source of arrhythmias in this model. Next we plan to characterize calcium homeostasis and electrical activity in the myocytes and Purkinje cells of these animals.
1. Single cardiac muscle cell force development and mechanics.
2. Single cardiac muscle cell intracellular calcium measurements. Whole cell calcium imaging as well as high temporal laser confocal microscopy.
3. Fluorescent monitoring of single cardiac muscle cell electrical properties.
4. Development of animal models of heart failure.
5. Classical biochemistry techniques including protein electrophoresis, Western Blotting, immunocytochemistry.
6. Molecular cloning, viral vector production, gene transfer.
Dr. Herron's publications are listed on PubMed. You can view them here.