“Alternative Polyadenylation in Cardiac Fibrosis: From Mechanism to Heart Failure Recovery"

Description: Heart failure remains difficult to treat because current therapies rarely reverse the cardiac fibrosis that limits myocardial recovery. This translational research examines alternative polyadenylation, a post-transcriptional mechanism that alters 3′ untranslated region (3′UTR) isoform usage and profibrotic gene expression. Studies integrate failing human myocardium, myocardial samples collected at left ventricular assist device implantation and subsequent heart transplantation, patient-derived cardiac fibroblasts, Poly(A)-ClickSeq, and mouse models. This approach defines how altered RNA processing promotes fibrosis and whether its reversal accompanies recovery following mechanical circulatory support, while evaluating gene-based strategies to restore protective 3′UTR usage, reduce fibrosis, improve cardiac function, and expand opportunities for patients with heart failure.

Rajarajan Amirthalingam Thandavarayan, M.Pharm., Ph.D.
Assistant Professor of Research
Department of Cardiology
Houston Methodist Research Institute
Assistant Professor in Cardiology Research
Weill Cornell Medical College