Researchers Receive NIH R01 Awards: Jeffrey A. Towbin, MD

Le Bonheur Cardiology Chief and Heart Institute Executive Co-director Jeffrey A. Towbin, MD, was awarded a Research Project Grant (R01) from the National Institutes of Health (NIH) with co-principal investigators Enkhsaikhan Purevjav, MD, PhD, and Lu Lu, MD, MS. He is lead principal investigator on the project “Discovery of Modifier Genes in Cardiomyopathy.”

The objective of this study is to identify the modifier genes that alter the expression of myopalladin (MYPN), a gene that affects the type and severity of cardiomyopathy – an inherited disease of the heart muscle that may ultimately result in heart failure, transplant or sudden cardiac death in many patients. The project will examine how different genetic backgrounds affect the mutation of the MYPN gene which determines how cardiomyopathy is expressed in children. The study will use systems genetics – an approach to understanding complex diseases by focusing on how genes work together rather than individually.

“Despite decades of research, it’s still difficult to predict how cardiomyopathy will present in a clinical setting,” said Towbin. “We believe that the likely reason for this is that the interaction of multiple genes – not just a single one – determines the course and severity of the
disease."

Previous research published by Towbin and Purevjav has screened adult and pediatric patients with various types of cardiomyopathy and identified MYPN as a strong causal gene associated with a wide variety of severity of cardiomyopathy. Patients had diagnoses ranging from asymptomatic left ventricular hypertrophy (thick heart) to left ventricular dilation and/or dilated atria with a stiff ventricle (restrictive physiology) with progressive heart failure to sudden cardiac death or transplant.

“Symptoms and forms of cardiomyopathy can be highly varied even within the same family who have identical genetic mutations,” said Towbin.

Identifying modifier genes is now a crucial goal of research in cardiomyopathies. Results of this study would change cardiomyopathy care in terms of diagnosis, treatment and genetic counseling. 

Towbin is conducting this research in conjunction with co-investigator Robert Williams, PhD, professor and chair of the Department of Genetics, Genomics and Informatics at UTHSC. Williams and Lu are responsible for performing studies and developing technologies necessary to perform the novel collaborative studies in this project.