Our lab studies molecular and in vivo mechanisms of cardiac regulation. We focus on the role of contractile proteins in modulation of mechanical and hemodynamic function in genetic and aquired heart failure. We use biophysical techniques, in vivo cardiovascular phenotyping, and gene replacement approaches to develop novel therapies that improve contractile function in heart failure.
Research Information
Research Interests
Cellular and molecular mechanisms of cardiac muscle contraction in health and disease
The major area of research in my lab is understanding the molecular mechanisms that govern the regulation of contractile function in the cardiac sarcomere. In particular, we are focused on unraveling the functional roles of contractile proteins in the modulation of force generation and cross-bridge kinetics in cardiac muscle. We study the functional effects of post-translational modifications of contractile proteins at the level of the myofilaments and in vivo whole organ function, and how genetic defects in these proteins lead to altered cross-bridge function and the development of impaired contractile function in vivo and ultimately dilated and hypertrophic cardiomyopathies. We employ a variety of molecular and biophysical techniques to study cross-bridge function and cardiac muscle mechanics. We utilize knockout and transgenic animal models as well as in vivo gene transfer techniques to study the functional roles of contractile proteins on in vivo cardiac function using echocardiography, pressure-volume catheterization, and magnetic resonance imaging.
Publications
- Bennett JS, Wood PT, Dominic KL, Moravec CS, Campbell KS, Stelzer JE. Functional Analysis of a Homozygous MYBPC3 Null Allele in Human Pediatric Patients. Circ Res. 137(9):1226-1228, 2025.
- Holmes JB, Stelzer JE. Comparative mechanistic analysis of danicamtiv and omecamtiv mecarbil's in vivo cardiac effects. J Gen Physiol. 157(4):e202513762, 2025.
- Schmidt AV, Thambidurai T, D'Annibale O, Bharathi SS, Wood T, Goetzman ES, Stelzer JE. Systemic Metabolic Rewiring in a Mouse Model of Left Ventricular Hypertrophy. Int J Mol Sci. 26(20):10111, 2025.
- Choi J, Wood PT, Holmes JB, Dominic KL, Dos Remedios CG, Campbell KS, Stelzer JE. Differential effects of myosin activators on myocardial contractile function in nonfailing and failing human hearts. Am J Physiol Heart Circ Physiol. 328(1):H161-H173, 2025
- Ananthamohan K, Stelzer JE, Sadayappan S. Hypertrophic cardiomyopathy in MYBPC3 carriers in aging. J Cardiovasc Aging. 4(1):9, 2024.
- Choi J, Holmes JB, Campbell KS, Stelzer JE. Effect of the Novel Myotrope Danicamtiv on Cross-Bridge Behavior in Human Myocardium. J Am Heart Assoc. 12(20):e030682, 2023.
- Holmes JB, Lemieux ME, Stelzer JE. Torsional and strain dysfunction precede overt heart failure in a mouse model of dilated cardiomyopathy pathogenesis. Am J Physiol Heart Circ Physiol. 325(3):H449-H467, 2023.
- Dominic KL, Choi J, Holmes JB, Singh M, Majcher MJ, Stelzer JE. The contribution of N-terminal truncated cMyBPC to in vivo cardiac function. J Gen Physiol. 155(6):e202213318, 2023.
- Mamidi R, KS Gresham, J Li & JE Stelzer. Cardiac myosin binding protein-C Ser(302) phosphorylation regulates cardiac ß-adrenergic reserve. Sci Adv 3:e1602445, 2017.
- Desjardins CL, Y Chen, AT Coulton, BD Hoit, X Yu & JE Stelzer. Cardiac myosin binding protein C insufficiency leads to early onset of mechanical dysfunction. Circ Cardiovasc Imaging 5:127-36, 2012.
- Mamidi R, KS Gresham, A Li, CG dos Remedios & JE Stelzer. Molecular effects of the myosin activator omecamtiv mecarbil on contractile properties of skinned myocardium lacking cardiac myosin binding protein-C. J. Mol. Cell. Cardiol. 85:262-72, 2015.
- Merkulov S, X Chen, MP Chandler & JE Stelzer. In vivo cardiac myosin binding protein C gene transfer rescues myofilament contractile dysfunction in cardiac myosin binding protein C null mice. Circ Heart Fail 5:635-44, 2012.
- Gresham KS & JE Stelzer. The contributions of cardiac myosin binding protein C and troponin I phosphorylation to ß-adrenergic enhancement of in vivo cardiac function. J. Physiol. (Lond.) 594:669-86, 2016.