The Umapathi Cardio-Metabolic Lab

Research Team

Gabriel Lopez-Cecetaite, Sc.M.

Gabriel is a recent Master of Science (ScM) graduate from the Johns Hopkins Bloomberg School of Public Health and joined the Umapathi lab as a Research Technician following his graduation from the program in May 2022. He received his BA in International Relations from Boston University and gained clinical experience working as a patient care technician at Beth Israel Deaconess Medical Center during his senior year. He has always been fascinated by the heart and circulatory system and hopes to attend medical school in the near future. In his free time, Gabriel enjoys running, biking, traveling, and trying to cook new recipes.

headshot of Gabriel Lopez-Cecetaite

Investigating Heart Failure

Every year, approximately 550,000+ Americans are diagnosed with heart failure. Half of these patients die within 5 years of diagnosis. Despite advances in medical therapy the prevalence of heart failure continues to grow exponentially. This has led to patients experiencing substantial morbidity and mortality and highlights the urgent need to identify novel pathophysiological mechanisms and improved therapies.

Heart failure is associated with changes in cardiac metabolism with several lines of evidence suggesting that a major metabolic pathway in the heart, the Hexosamine Biosynthesis Pathway, exerts an impactful role. The product of the pathway is involved in the post-translational modification of cardiac proteins, a process known as O-GlcNAcylation, and plays a key role in the response of the heart to stress, regulating both health and disease.

We discovered chronic exposure to increased O-GcNAcylation causes heart failure, whereas decreased O-GlcNAcylation can protect the heart. However, work remains to develop detailed understanding of how O-GlcNAcylation contributes to heart health and disease.

Our lab hopes to bridge this gap in knowledge to refine our understanding of cardiac O-GlcNAcylation, metabolism and energetics to evolve the use of cardiac O-GlcNAc biology to discover heart failure mechanisms, diagnostics and therapeutics.

Research Projects

O-GlcNAcylation occurs on thousands of proteins in the heart and is regulated by only two enzymes, the O-GlcNAc Transferase or OGT (adds modification) and the O-GlcNAcase or OGA (removes modification). Myocardial O-GlcNAcylation is increased in failing hearts, but it was unknown if increased O-GlcNAcylation was a cause of heart failure. To answer this question, we developed novel lines of transgenic mice overexpressing either OGT, or OGA, in myocardium. OGT hearts have more OGN and these mice have myocardial hypertrophy, heart failure and die prematurely from arrhythmias. In contrast, OGA animals have less OGN and are protected against cardiac stress.

Selected Publications

  • Stawiarski K, Avery R, Strout S, Umapathi P. Risks of paxlovid in a heart transplant recipient. J Heart Lung Transplant. 2023 Jan;42(1):30-32. 
    doi: 10.1016/j.healun.2022.08.029. Epub 2022 Sep 8. PubMed PMID: 36344373; PubMed Central PMCID: PMC9452411.
  • Umapathi P, Mesubi OO, Banerjee PS, Abrol N, Wang Q, Luczak ED, Wu Y, Granger JM, Wei AC, Reyes Gaido OE, Florea L, Talbot CC Jr, Hart GW, Zachara NE, Anderson ME. Excessive O-GlcNAcylation Causes Heart Failure and Sudden Death. Circulation. 2021 Apr 27;143(17):1687-1703. 
    doi:10.1161/CIRCULATIONAHA.120.051911. Epub 2021 Feb 17. PubMed PMID: 33593071; PubMed Central PMCID: PMC8085112.

Heart Failure Society of America HF Beat

Priya Umapathi is a 2022 Social Media Catalyst for HFSA and co-host of the HF Beat Podcast – Come listen to the latest and greatest in heart failure science!Each month, join the Heart Failure Society of America as we have candid conversations with heart failure clinicians on the topics they face on a daily basis. From breakthroughs in research and treatment to career development and growth, the Heart Failure Beat has you covered! If you’re a cardiology clinician, trainee, or just plain interested in hearing discussions about heart failure news from leading experts, this is the podcast for you!