The ASPIRE Path in Molecular Medicine

Cadherin-11, the most mechanically robust cadherin, is highly expressed in heart valves and the non-cardiomyocyte cells of the infarcted heart. Its expression can result in the activation of signaling pathways that promote inflammatory invasion in fibrotic diseases like cardiac fibrosis. I propose that developing treatments specifically targeting cadherin-11 can regulate cardiac disease. This will include the utilization of siRNA therapies. Since siRNA is subjected to degradation within serum and accumulates primarily in the kidney, I am developing a method that incorporates peptide nucleic acid (PNA) to bridge siRNA with a cadherin-11 targeting peptide. This will give a controlled mechanism to attach the peptide to siRNA without hindering siRNA activity and also allow for delivery to the heart. I believe that the development of this strategy will be a novel therapy for heart valve calcification which can be later used in human test subject trials once successfully developed.