Developing new drugs for heart disease

This project outlines a plan to prevent organ damage associated with ischemic injuries of the heart. There are no drugs that prevent organ damage caused by these injuries, which ultimately leads to heart failure, making ischemic heart disease the leading cause of death worldwide. This project aims to identify new molecular targets coupled with development of a novel pharmacological inhibitors as novel therapeutics to promote rapid and more effective recovery following an acute cardiovascular event. Development of new cardiovascular drugs will address a major clinical area of unmet need, thereby decreasing mortality, improving recovery and quality-of-life for survivors, and drastically reducing the burden of these diseases.

Conditions caused by obstruction of blood flow to the heart are the most common emergency manifestation of cardiovascular disease. Although acute reperfusion therapies have improved patient outcomes, mortality remains high and heart attacks are one of the largest attributable risks for heart failure (HF). Myocardial sensitivity to ischemia-reperfusion injury (IRI) therefore remains a primary point of vulnerability underlying cardiovascular disease, which is the leading cause of morbidity and mortality worldwide. Despite decades of preclinical therapeutic development, there are no drugs in clinical use that block the acute injury response to cardiac ischemia.

My research group has discovered a new therapeutic drug to prevent injuries of the heart, a peptide (Hi1a) isolated from venom of the Fraser Island funnel-web spider. Hi1a is a safe and potent therapeutic that we have shown improves heart recovery after myocardial infarction (MI) and greatly enhances the performance of donor hearts procured for transplantation. These remarkable therapeutic properties stem from Hi1a’s ability to protect heart muscle cells from ischemic injury by inhibiting an ion channel known as acid-sensing ion channel 1a (ASIC1a).
More broadly, my research program is advancing studies on Hi1a alongside development of other novel therapeutic drugs that reduces the scope and spread of organ injury to the heart after ischemic injuries. These research projects integrate information from diverse sources to establish rationale and mechanism including population statistical genetics methods (e.g. GWAS), CRISPR genetic perturbation studies in iPSCs, functional studies in cell models, and animal models of disease.  

Relevant lab publications of interest:

1.    Redd MA, Scheuer SE, Saez NJ, Yoshikawa Y, Chiu HS, Gao L, Hicks M, Villanueva JE, Joshi Y, Chow CY, Cuellar-Partida G, Peart JN, See Hoe LE, Chen X, Sun Y, Suen JY, Hatch RJ, Rollo B, Alzubaidi MAH, Maljevic S, Quaife-Ryan GA, Hudson JE, Porrello ER, White MY, Cordwell SJ, Fraser JF, Petrou S, Reichelt ME, Thomas WG, King GF*, Macdonald PS*, Palpant NJ*. Therapeutic inhibition of acid sensing ion channel 1a recovers heart function after ischemia-reperfusion injury. Circulation. 2021;144:947–960