Research Projects

Myocardial Infarction (MI) is the leading cause of morbidity and mortality worldwide. Each year, over 3 million individuals experience ST-segment Elevation Myocardial Infarction (STEMI)[1]. Early diagnosis—ideally within 12 hours in cases of ventricular blockage—can significantly improve prognosis. However, timely diagnosis is often unachievable, and in such cases, reperfusion therapies such as fibrinolysis are administered[2]. In most cases, MI leads to the replacement of dead contractile myocardium with non-contractile, collagen-rich fibrotic tissue, ultimately impairing heart function[3]. Currently, no therapies exist that can fully restore cardiac function after myocardial damage[4]. In contrast to mammals, certain lower vertebrates such as salamanders, axolotls, and zebrafish are capable of efficient cardiac regeneration[5,6,7]. Understanding the molecular and cellular mechanisms underlying this regenerative capacity could inform the development of novel therapeutic strategies for MI patients. Integrins are heterodimeric adhesion receptors that regulate key cellular behaviours—including proliferation, differentiation, and migration[8]—through bi-directional signalling:Inside-out signalling, which modulates integrin ligand affinity[8] and Outside-in signalling, which transduces extracellular signals to regulate cellular responses[8].In mammals, integrins consist of 24 transmembrane heterodimers formed by combinations of 18 α and 8 β subunits[9]. Several studies have highlighted the role of specific integrins in cardiac pathology. For instance, activation of β3 integrin induces fibronectin and collagen secretion by cardiac fibroblasts[10]. Angiotensin II has been shown to promote expression of integrins αVβ3 and α8β1 in vascular smooth muscle cells and cardiac myofibroblasts[11,12]. Additionally, fibronectin upregulates β1 integrins in cardiac fibroblasts, underscoring the relevance of β1 integrin in post-MI remodelling[13,14]. Notably, overexpression of nephronectin—a ligand for integrin α8β1—has been shown to improve cardiac function after MI by enhancing angiogenesis and reducing scar tissue[15]. Despite this evidence, the role of integrin α8, a known partner of β1, in cardiac regeneration remains poorly understood. Unpublished gene expression data from Dr. Patra’s lab have shown that itga8 is expressed in developing zebrafish hearts and is upregulated in adult hearts following myocardial injury, suggesting a potential role in regeneration. Furthermore, Dr. Patra’s lab has successfully generated itga8 knockout zebrafish using CRISPR/Cas9 technology, and these mutants are viable in adulthood. In this study, we propose to investigate the spatiotemporal expression pattern and the role of itga8 in heart regeneration using these adult itga8 loss-of-function zebrafish mutants. This work has the potential to uncover novel regenerative pathways that could be targeted for developing therapeutic strategies aimed at improving heart function.