The Umapathi Lab is dedicated to discovering and altering mechanisms that lead to heart failure. We study how the modification of cardiac proteins intersects with cardiac metabolism and energetics leading to the development of cardiac dysfunction. We use novel tools for cardiac contractility and arrhythmia to perform molecular phenotyping in both acquired (diabetic, ischemic, hypertensive, metabolic) or inherited forms of heart disease. Our goal is to identify novel heart failure targets, refine heart failure diagnostic platforms and develop translational therapeutics to advance care for patients.
Research Team
Seungyeon Julie Lee
Research Technologist
Julie earned her bachelor’s degree in Molecular and Cellular Biology from Johns Hopkins University. As an undergraduate, she conducted research in Dr. Xin Chen’s lab, investigating the role of MCM2 in establishing asymmetric chromatin environments during asymmetric cell division. In the summer of 2024, she joined Dr. Umapathi’s lab as a research technologist and is investigating connections between O-GlcNAcylation and heart failure using in vivo and in vitro models. She aspires to be a physician-scientist who advances patient care through translational research. In her free time, she enjoys exploring cafes and bakeries to try new drinks and pastries.
Ernesto Marin
Medical Student
Ernesto is a medical student at Johns Hopkins University School of Medicine, born and raised in Miami, Florida. He is interested in exploring novel circulating biomarkers for heart failure and helping to advance precision medicine into cardiac care. In his free time, he enjoys playing basketball, taking long outdoor walks, and reading.
Harriet He
Harriet is a first year Master's student in the Biomedical Engineering program at the Johns Hopkins Whiting School of Engineering. She joined the Umapathi lab as a research mentee in October 2024. Harriet received her BS in Bioinformatics from the University of Michigan, Ann Arbor with a minor in Data Science. She is fascinated by spatial transcriptomics, and she is particularly interested in applying computational approaches to analyze how enzymes regulate protein O-GlcNAcylation patterns. Harriet plans to pursue a PhD in the near future. In her free time, Harriet enjoys skiing, skateboarding, and hanging out with her cat, Ananas, an 18 lb Maine Coon.
Akshita Kikkuru
Undergraduate Student
Akshita is a pre-med undergraduate student at Johns Hopkins University studying Molecular and Cellular Biology and Public Health. She has always been fascinated by the cardiovascular system and the mechanisms that regulate cardiac function and disease. In addition to her research, she serves as a patient advocate at Johns Hopkins Hospital, connecting Baltimore families with essential resources to address social determinants of health.
Gabriel Lopez-Cecetaite
Former Research Technologist
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.
Research 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.
Research Projects
Laboratory Research
O-GlcNAcylation and Cardiac Energetics
Both major clinical subtypes of heart failure (Heart Failure with Reduced Ejection Fraction and Heart Failure with Preserved Ejection Fraction) are associated with derangements in cardiac metabolism and energetics. In heart failure, there is often an impairment in fatty acid metabolism and a shift toward glucose oxidation, with enhanced reliance on glucose utilization pathways like the HBP and an increase in O-GlcNAcylation. Our lab uses transgenic and pathologic murine models and metabolomic/proteomic data to study the role of metabolites, preferential mitochondrial substrate utilization, and energetic re-programming in heart failure.
O-GlcNAcylation and Cardiac Remodeling
To explore the intersection of O-GlcNAcylation and cardiac hypertrophy, we manipulate cardiac cells to have either excess or reduced O-GlcNAcylation. Using microscopy, we then examine changes in the nuclear and cytoplasmic localization of proteins involved in hypertrophy.Pathological hypertrophy is commonly antecedent to clinical heart failure. Myocardial O-GlcNAcylation is a recently discovered mechanism causing pathological hypertrophy and heart failure. Our lab uses innovative genetic mouse models that control myocardial O-GlcNAcylation levels independent of cardiac stress, mass spectrometry and proteomics, to understand the impact of O-GlcNAc on pro-hypertrophic and heart failure mechanisms.
Translational Projects
Clinical Precision Proteomic Profiling for Heart Failure
As heart failure diagnoses and therapies expand, the need for precision medicine is growing. Proteins are powerful mediators of disease and can serve as clinical biomarkers, used to diagnose and guide treatment. We study the role of O-GlcNAc-modified proteins in heart failure patients using a bedside-to-bench approach, with the aim of developing a novel precision proteomic platform for heart failure patients.
Cardio-Energetic Reprogramming in Heart Failure
Sodium-Glucose Transporter 2 inhibitors (SGLT2i) have dramatically changed the treatment of clinical heart failure. However, the mechanistic cardiac targets of these drugs are poorly understood. Our lab studies the role of SGLT2i, the Hexosamine Biosynthesis Pathway, and O-GlcNAcylation in heart failure.
Selected Publications
- * 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. *corresponding author
- Reyes Gaido OE, Nkashama LJ, Schole KL, Wang Q, Umapathi P, Mesubi OO, Konstantinidis K, Luczak ED, Anderson ME. CaMKII as a Therapeutic Target in Cardiovascular Disease. Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:249-272. doi: 10.1146/annurev-pharmtox-051421-111814. Epub 2022 Aug 16. PMID: 35973713
- Scheel PJ 3rd, Giuliano K, Tichnell C, James C, Murray B, Tandri H, Carter D, Fehr T, Umapathi P, Vaishnav J, Lewsey SC, Hsu S, Calkins H, Sharma K, Choi CW, Gilotra NA, Kilic A. Heart transplantation strategies in arrhythmogenic right ventricular cardiomyopathy: a tertiary ARVC centre experience. ESC Heart Fail. 2022 Apr;9(2):1008-1017. doi: 10.1002/ehf2.13757. Epub 2021 Dec 24. PMID: 34953065; PMCID: PMC8934913.
- 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. PMID: 36344373; PMCID: PMC9452411.
- Narayanan B, Zahra F, Reeves RA, Aggarwal A, O'Meally RN, Henry RK, Craven M, Jacobson A, Cole RN, Kohr MJ, Umapathi P, Zachara NE. Differential Detection of O-GlcNAcylated proteins in the heart using antibodies. Anal Biochem. 2023 Oct 1;678:115262. doi: 10.1016/j.ab.2023.115262. Epub 2023 Jul 27. PMID: 37507081
- Umapathi P, Aggarwal A, Zahra F, Narayanan B, Zachara NE. The Multifaceted Role of Intracellular Glycosylation in Cytoprotection and Heart Disease. J Biol Chem. 2024 Apr 17:107296. doi: 10.1016/j.jbc.2024.107296. Epub ahead of print. PMID: 38641064.
- Kim YJ, Gami A, Schumacher S, Belanger M, Umapathi P. Protein-Losing Enteropathy and CD4+ T-Cell Immunodeficiency Complicated by Listeria monocytogenes Constrictive Pericarditis. JACC Case Rep. 2024 Aug 21;29(16):102463. doi: 10.1016/j.jaccas.2024.102463. PMID: 39295798; PMCID: PMC11405948.
