Naomi Chesler Receives $4.9 Million NIH Grant for Right Ventricular Failure Research

July 16, 2026 - The lifetime risk for heart failure in the United States is 24 percent, and that risk is growing.  Historically right ventricular failure, where the right side of the heart loses its ability to effectively pump blood to the lungs, has been understudied with clinical research focusing primarily on the left. There are also intriguing sex differences in right ventricular failure that are not evident in left ventricular failure and remain poorly understood.      

UC Irvine Chancellor's Inclusive Excellence Professor Naomi Chesler has been awarded a $4.9 million grant from the National Institutes of Health to continue her research into RVF using a combination of experiments in rodent models of disease, human tissue, and computational multi-scale modeling.  Their model integrates heart dysfunction at multiple scales, including at the organelle, tissue, organ and organism levels, exploring how various dysfunctions contribute to RVF.  

“ I started studying the right ventricle many years ago because women are diagnosed with RVF more often than men but often live longer with the disease. This sex difference, plus the fact that the right side of the heart is understudied relative to the left, speaks to my passion for using my engineering skills to advance cardiovascular health equity,” said Chesler. “This particular project is a great example of teamwork, with four principal investigators contributing unique skills, techniques, and knowledge, to make a whole that is stronger than the sum of its parts. I am excited to continue this impactful research in partnership with colleagues at the University of Michigan Professor Dan Beard, University of California San Francisco Professor Anthony Baker, and University of Kentucky Professor Ken Campbell.”

Chesler is a UCI professor of biomedical engineering and the director of the Edwards Lifesciences Foundation Cardiovascular Innovation and Research Center which leads synergistic and interdisciplinary research in cardiovascular science and engineering with the goal of accelerating advances in cardiovascular health and health equity.    

Their RVF research has three primary aims:

Aim 1: Mapping Metabolic Dysfunction in RV Failure In Vivo

First, the researchers are striving to determine the causes and consequences of metabolic dysfunction in RV failure in living subjects. They are studying how pressure overload — the intense physical strain placed on the heart when it has to pump against high resistance — triggers mitochondrial energetic derangement, a breakdown in a heart cell’s ability to efficiently turn oxygen and food into energy. They will study this in rats by looking at what happens to heart function when the gene adenosine monophosphate deaminase 3 is disabled and when a drug blocks a key enzyme, glucose-6-phosphate dehydrogenase.

Aim 2: Translating Cellular Mechanics to Human Disease

Second, they will study the direct link between organelle and tissue-level dysfunction in myocardial samples from both humans and rats in vitro. They will assess how well the heart muscle tissue generates force and power under different energy conditions by varying the levels of the tissue’s key energy molecules: ATP, ADP, and Pi.

The team will integrate the human tissue data into a human version of their computer model. By pairing this “digital twin” with clinical data linked to the human tissue samples, they can link this microscopic heart muscle behavior to human disease.

Aim 3: Building the Multiscale Virtual Heart

Lastly, they are developing computational models that incorporate their findings in coupled myocardial metabolism and mechanics. These computer simulations will integrate the key pathways of cardiac energy and mechanics to predict dysfunction at every level — from the subcellular level to the whole organ. These simulations will test the researchers’ theories about metabolic effects on myocardial tissue and ventricular mechanical function.

This combination of experiments and multiscale computational modeling aims to enable researchers to gain insight into right ventricular failure.

- Natalie Tso