Hypertrophic Cardiomyopathy

A Department of Medicine Research Spotlight

Professor of Medicine, Division of Cardiology / Sarver Heart Center
Professor of Cellular and Molecular Medicine
Vice Chair for Research, Department of Medicine

I’m a practicing physician-scientist. My work focuses on the pathogenesis of Hypertrophic Cardiomyopathy (HCM), a disorder affecting one out of every 500 individuals worldwide. HCM is an autosomal dominant genetic disorder caused by mutations in the proteins that comprise the cardiac sarcomere and is one of the most common causes of sudden cardiac death in young people.

Work in my lab utilizes an integrative physiologic and biophysical approach to delineate underlying links between structural and functional alterations in cardiac thin filament proteins and the resultant complex cardiovascular phenotypes. We and others have shown that the molecular effects of independent gene mutations in contractile proteins are varied and disrupt both sarcomeric function and myocellular signaling pathways leading to the complex, often progressive cardiac remodeling that characterizes HCM. My position as the director of the Hypertrophic Cardiomyopathy Clinic at Banner – University Medical Center Tucson (the only HCM clinic in the Southwest) affords me a unique opportunity to both care for these complex patients and incorporate my understanding of their clinical course into my research program with a long-term goal of developing novel therapeutics for this not uncommon disorder. The process of linking known thin filament mutations to progressive cardiomyopathic remodeling requires a broad range of techniques and experimental systems in order to study this primary biophysical disorder at multiple resolutions. Thus, my group utilizes many different approaches ranging from all-atom level computational modeling to Förster Resonance Energy Transfer (FRET) structural analyses and transgenic mouse models of cardiac disease to fully explore the complex pathogenic mechanisms of HCM. While these techniques seem highly specialized, I encourage housestaff to get involved at any level and am committed to developing an investigative program that promotes their academic potential to the fullest.

Project 1: Assist with the clinical workup of a patient with HCM, arrange for whole exome sequencing analysis for the family at the University of Arizona Genetics Core, learn about segregation analysis and identification of potential pathogenic gene mutations and help to design approaches for further study including RNA-Seq, iPSC myocyte development and in vitro analysis.

Project 2: Choose a novel protein mutation and study the potential structural and functional effects of the mutation at the molecular level using cell biology and basic biophysical assays.

Release Date: 
03/08/2016 - 11:00am