Research Description

My research focuses on uncovering how transcriptional mechanisms contribute to the development of heart disease, particularly in the setting of hypertension. I study the Mediator kinases Cdk8 and Cdk19, which are enzymes within the Mediator complex that regulate gene expression by modifying transcriptional enhancers and phosphorylating key regulators such as Stat1, Brd4, and Mef2d. Our preliminary studies show that these kinases are elevated in both human and mouse models of heart failure, suggesting they play a central role in driving pathological changes in the heart. To test this, I use mouse models of cardiac hypertrophy along with small-molecule inhibitors that target Mediator kinase activity, assessing their effects on cardiac structure, function, and gene expression. I also use biochemical and genomic approaches to map enhancer activity and identify kinase-dependent signaling pathways that reprogram gene networks under stress. By defining these molecular mechanisms, my goal is to establish Mediator kinase activity as a key regulator of the transition from normal to diseased cardiac states. Ultimately, this research may provide a foundation for new therapeutic strategies that target transcriptional control to prevent or reverse pathological hypertrophy and reduce the burden of heart failure.

Publications

Henry KM, Gardner RN, Oppman AM, Daneshgar N, Rosales M, Martins I, Baskin KK, Grueter CE. Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression. J Mol Cell Cardiol Plus. 2025 Aug 31;13:100481. doi: 10.1016/j.jmccpl.2025.100481. PMID: 40989238; PMCID: PMC12451381.

Kumar A, Zhao Y, Xie L, Chadda R, Tranter JD, Mikami RT, Abraham N, Hong J, Feng E, Rawnsley DR, Liu H, Henry KM, Meyer G, Hu M, Xu H, Hinton A Jr, Grueter CE, Abel ED, Norris AW, Diwan A, Sah R. Lysosomal LRRC8 complex impacts lysosomal pH, morphology, and systemic glucose metabolism. Sci Adv. 2025 Sep 26;11(39):eadt6366. doi: 10.1126/sciadv.adt6366. Epub 2025 Sep 26. PMID: 41004571; PMCID: PMC12466849.

Leinheiser AK, Nguyen TT, Henry KM, Rosales M, Van Otterloo E, Grueter CE. Heterozygous Med13l mice recapitulate a developmental growth delay and craniofacial anomalies seen in MED13L syndrome. Dev Dyn. 2025 Sep 8. doi: 10.1002/dvdy.70079. Epub ahead of print. PMID: 40919805.

Honors and Awards

Genetics T-32 Pre-doctoral Training Grant (2024 - 2025 and 2025 - 2026)

Abboud Cardiovascular Research Center Best Trainee Presentation (2024)