My research is focused on determining molecular mechanisms of heart disease and finding new ways to treat heart disease. One new technology that has emerged and holds much promise for novel therapies to treat heart disease is induced pluripotent stem cell technology. It is now possible to transform patient skin cells into pluripotent stem cells. These induced pluripotent stem cells have the capacity to differentiate into any cell of the human body, including cardiac muscle cells. Our research shows that when formed into multicellular tissue like patches these de novo cardiac cells beat uniformly together at rates similar to the adult human heart. We are now trying to determine the optimal bioengineering approaches to generate cardiac tissue in vitro that can be used for disease modeling, drug testing and cardiac regeneration therapies.
Heart failure affects nearly 5 million citizens in the United States. Currently the only cure is cardiac transplantation and there is a lack of donor hearts to meet demand. Induced pluripotent stem cells can be created from patients' skin fibroblasts, thus creating a virtually unlimited supply of patient specific stem cells that can be used to for cardiac regeneration purposes. However, the optimal conditions to bioengineer cardiac constructs that might repair failing hearts are unknown. The goal of my reserach is to determine the optimal three dimensional (3D) culture and growth conditions to create clinically useful cardiac patches. In this endeavor I collaborate with cardiac electrophysiologists and biomedical engineers.
Simultaneous voltage and calcium mapping of genetically purified human induced pluripotent stem cell-derived cardiac myocyte monolayers.Lee P, Klos M, Bollensdorff C, Hou L, Ewart P, Kamp TJ, Zhang J, Bizy A, Guerrero-Serna G, Kohl P, Jalife J, Herron TJ. Circ Res. 2012 Jun 8;110(12):1556-63. Epub 2012 May 8.
Optical imaging of voltage and calcium in cardiac cells & tissues. Herron TJ, Lee P, Jalife J.Circ Res. 2012 Feb 17;110(4):609-23.
Loss of H3K4 methylation destabilizes gene expression patterns and physiological functions in adult murine cardiomyocytes. Stein AB, Jones TA, Herron TJ, Patel SR, Day SM, Noujaim SF, Milstein ML, Klos M, Furspan PB, Jalife J, Dressler GR. J Clin Invest. 2011 Jul;121(7):2641-50
Gene transfer, expression, and sarcomeric incorporation of a headless myosin molecule in cardiac myocytes: evidence for a reserve in myofilament motor function. Vandenboom R, Herron T, Favre E, Albayya FP, Metzger JM. Am J Physiol Heart Circ Physiol. 2011 Feb;300(2):H574-82.
Purkinje cell calcium dysregulation is the cellular mechanism that underlies catecholaminergic polymorphic ventricular tachycardia. Herron TJ, Milstein ML, Anumonwo J, Priori SG, Jalife J. Heart Rhythm. 2010 Aug;7(8):1122-8