My interests in the lab involve characterizing the major signaling networks and cardiac progenitors/cell types that are involved in building the embryonic heart. By shedding light on such mechanisms and cell types involved in mammlian cardiogenesis, we may more easily be able to highlight whether a natural repair system exists in the developing fetal heart, which could then be coaxed to repair genetically diseased hearts.
Our team has established a novel gain of function tool based on chemically modified mRNAs, which evade activation of innate immune responses and provide targeted transient expression in the heart. I am currently building a library of stabilized modRNAs, where the functional affects of modRNA candidates are first tested in human embryonic stem cell - derived cardiomyocytes. The functional elucidation of novel gene candidates will be used in small and large scale MI models of heart disease and heart failure, where ultimately the modRNA technology will help us to evaluate the roles of paracrine factors and intracellular signals involved in cardiac development and regeneration.
Complimenting the in vitro affects of modRNAs on cardiac cell types, we are also performing ultrasound mediated delivery of modRNA in vivo. In order to manipulate cardiogenesis at different developmental time points, live imaging of embryonic hearts are performed using ultra-sound equipment in tangent with a micro-injector apparatus for the localized delivery of modRNAs in-utero. Currently, early fetal cardiac interventions are severely lacking and we hope the knowledge gained from such studies could go some way to correcting congenital heart disorders.
Lastly, I am collaborating with the Simon group to see if we can unravel the mystery of an intrinsic cardiac regeneration response using a lower vertebrate model system, the salamander.