BIDMC cardiology team receives $3 million NIH grant to identify microRNA biomarkers

A research team led by Principal Investigator Saumya Das, MD, PhD, an electrophysiologist in the CardioVascular Institute at Beth Israel Deaconess Medical Center (BIDMC), has received a $3 million grant renewal from the National Institutes of Health (NIH) program in Extracellular RNA Communication. The funding will support ongoing work to identify microRNA molecules that can serve as biomarkers to help predict outcomes in patients with heart disease.

The grant provides the second phase of support for the team's original project, "Plasma miRNA Predictors of Adverse and Electrical Remodeling After Myocardial Infarction," which launched in 2013 with $4 million in funding from the NIH.

"Each year, complications from heart attacks [myocardial infarctions] contribute to more than 550,000 cases of heart failure and 300,000 cases of sudden cardiac arrest," said Das. "Both of these conditions are closely related to a process known as remodeling, in which the structure and function of the heart changes - or remodels - following a heart attack."

Das, who is a faculty member in BIDMC's Institute for RNA Medicine, conducts research on a type of extracellular RNA called microRNAs. These small, noncoding RNAs have only recently been identified in blood and other tissues, and Das has been exploring the role that these tiny molecules play in in predicting which heart-attack patients might go on to develop remodeling complications.

"Over the past two years, we have been using RNA sequencing technology to identify characteristics in extracellular RNAs in plasma that might enable us to better predict patient outcomes following a heart attack," said Das. "Our ultimate goal is to use microRNA-based tests to predict which patients might be at risk of complications related to remodeling," said Das. "That way we can more aggressively monitor their conditions and intervene with medications or implantable devices if needed."

The team has completed the first phase of the project, and has identified a number of microRNA biomarker candidates. In line with their recently published work, they have found that one of these molecules, microRNA-30d, is an important predictor of beneficial cardiac remodeling in patients following a heart attack.

"Even more important, we've found that microRNA-30d plays a functional role in preventing cell death," said Das. "We think that having higher levels of this microRNA is an adaptive response to the increased stress of heart failure and allows cardiac cells to better remodel. We're now incorporating this new discovery in studies in mice to see if microRNA-30d can serve as a therapy to protect against different models of heart disease."

Together with project leaders Raymond Y, Kwong, MD, MPH, and Mark Sabatine, MD, MPH, of Brigham and Women's Hospital, and Anthony Rosenzweig, MD, of Massachusetts General Hospital, Das will now investigate microRNA-30d along with other extracellular RNA candidates to validate this discovery in several large patient cohorts.

Other BIDMC investigators who are part of this project include Ravi Shah, MD, a clinician in BIDMC's Advanced Heart Failure Program and Kirsty Danielson, PhD, a postdoctoral fellow in the Das laboratory.

Provided by Beth Israel Deaconess Medical Center