Necla Erdogan Rose Hills
Myosin Isoform Switching as a Therapeutic Strategy in Myocarditis
Myocarditis is a rare autoimmune condition defined by an accumulation of T cells and macrophages in the heart with associated cardiomyocyte death. It presents with a spectrum of severities including fulminant cardiac dysfunction and despite decades of research, has no effective therapies. I will use my lab’s highly penetrant spontaneous model of murine myocarditis where two T cell immune checkpoint molecules (Lag3 and PD1) have been genetically eliminated. The T cells infiltrating the heart recognize the cardiac protein, α-myosin. Interestingly, this protein’s paralog, β-myosin despite sharing 93% amino acid sequence similarity, is non-immunogenic. For my summer research, I will take advantage of the observation that hypothyroidism induced by a modified diet in mice causes a nearly complete transition between the myosin isoforms from α- to β- without affecting overall health. Reducing α-myosin expression should prevent myocarditis development and, although inducing severe clinical hypothyroidism in humans is unlikely to be a useful therapy, the concept of shifting myosin expression would introduce a new potential treatment paradigm warranting further exploration.
Message To Sponsor
I am incredibly grateful to everyone who made this research opportunity possible for me. I am excited for the chance to develop as a scientist and contribute to an ever growing field. I have full confidence I will make the most of it and can’t wait to share what I learn!