- Email: email@example.com
- Phone: (775) 784-8253
- Office: Howard Medical Sciences 217
- Ph.D., University of Washington, 1998
Sudden cardiac death kills as many as 300,000 Americans every year, and in most cases the ultimate demise of the individual is due to the abrupt onset of abnormal electrical activity or cardiac arrhythmia. Even though the incidence of sudden cardiac death is often associated with some sort of preexisting condition, a significant number of victims have no apparent underlying cardiovascular disease. The critical, yet unanswered, question is what triggers fatal arrhythmias in these individuals? Although the mechanisms responsible remain largely unknown, there is substantial evidence that heart-brain interactions involving the autonomic nervous system play a critical role in many cases. Our working hypothesis is that dynamic interactions between the sympathetic and parasympathetic branches of the autonomic nervous system trigger abnormal electrical responses that can lead to the generation of life threatening ventricular arrhythmias. We believe that these abnormal responses are due to complex subcellular signaling mechanisms that affect the activity of a number of different ion channels in the heart. To test our hypothesis, we are using a systems biology approach that combines computational modeling with a variety of powerful experimental techniques. These include single cell recording of membrane currents and action potentials as well as live cell imaging of subcellular signaling responses using fluorescence resonance energy transfer (FRET) based biosensors. The ultimate goal is to identify the conditions under which imbalances in autonomic tone are likely to trigger ventricular arrhythmias in order that they might be prevented.
The long-term goal of my laboratory is to understand the molecular mechanisms regulating phenotypic plasticity in smooth muscle cells. Phenotypic plasticity is a phenomenon by which mature contractile smooth muscle cells reversibly switch to an immature synthetic phenotype, which can result in the production of inflammatory mediators coupled with changes in cell numbers and mass. Our laboratory was one of the first to describe miRNA expression in human airway smooth muscle cells and have identified miR-25 as a target of phenotypic plasticity in this cell type. We are currently investigating the mechanisms by which miR-25 and other miRNAs regulate airway smooth muscle phenotype in culture by studying inflammatory, proliferative and contractile functions of airway smooth muscle cells. We are also developing a transgenic animal model of miR-25 expression to study the role of this miRNA on lung function in an animal model of allergic asthma.
We are currently furthering our study of miRNA in other smooth muscle cell types. Our laboratory collaborates with the Myometrial Function Group to explore the regulation of miRNA in human uterine smooth muscle function. The goal of this work is to identify gene-silencing pathways leading to the onset of pre-term labor. We are examining miR-25 function is vascular smooth muscle cells to determine whether miR-25 expression affects smooth muscle phenotypes relevant to cardiovascular disease.