Reilly Group: Atrial Fibrillation and Cardiac Fibrosis: from molecular signalling to drug discovery.

 Atrial fibrillation (AF) is an increasingly common arrhythmia that is associated with significant morbidity and a two-fold increase in mortality. Treatment of AF remains a challenge, as AF induces electrical and structural changes in the atrial myocardium. The mechanisms of  remodelling are not well understood; however, microRNAs (small non-coding RNAs) have emerged as important players in this process. We are very interested in uncovering patho- and physio-logical role of microRNAs in AF, with a particular focus on studying microRNA-mediated function of cardiac fibroblasts.

1. Investigating microRNA-mediated mechanisms of cardiac fibrosis.

Cardiac fibrosis is a prominent feature of cardiac pathology (including AF) and is a major unmet clinical problem. Through our research we explore the mechanisms causing and underlying atrial fibrogenesis so as to inform new tools to control excessive fibrosis. Of a particular interest is microRNA-31 which is upregulated in the atria of patients with atrial fibrillation and drive pro-arrhythmic /pro-fibrotic phenotypes in the heart. Thus, we aim to uncover fibroblasts-specific donwstream targets of microRNA-31 and investigate the impact of microRNA-31 on fibrogenesis in AF using isolated human and murine cardiac fibroblasts (Fig.1). We will employ functional assays to assess cell viability, migration, stress fibre formation and proliferation, collagen production (Fig.2) and calcification of extracellular matrix. As a part of this work, we are also interested in exploring the interplay between cardiac myocytes and fibroblasts using isolated cardiomyocytes.

Figure 2: Collagen production by human atrial fibroblasts in culture (assessed by scar-in-a-jar assay, curtesy of Dr Angela Lee)

2. Investigating calcitonin signalling in atrial fibrillation (AF) and cardiac fibrosis

We have recently uncovered that the atrial chambers of the human heart serve as an unexpected and previously unrecognised source of the hormone calcitonin—traditionally thought to originate primarily from the thyroid. Strikingly, we found that calcitonin signalling is markedly impaired in atrial fibrillation (AF), and that restoring this pathway may open an entirely new therapeutic avenue for patients with AF and related fibrotic disease. Our current research aims to unravel the mechanisms driving this suppressed signalling and to identify druggable targets capable of reactivating the calcitonin–calcitonin receptor axis.

To tackle these questions, we integrate clinical cardiac biopsy and blood samples with cutting-edge molecular and cell biology, multi-omics profiling, and advanced confocal imaging. Our drug-discovery efforts are further strengthened through close collaboration with the Target Discovery Institute (Oxford) and industry partners. This fast-moving programme offers exciting opportunities for DPhil projects at the interface of cardiovascular biology, translational science, and therapeutic innovation.

3. Drug discovery for AF and fibrosis

In this subtheme, we focus on translating our fundamental discoveries in cardiac remodelling and fibroblast biology into novel therapeutic strategies for atrial fibrillation (AF) and cardiac fibrosis. By integrating molecular profiling, high-throughput screening, and disease-model systems, we aim to identify and validate new drug targets that can modify disease mechanisms rather than simply manage symptoms. This programme offers opportunities for DPhil projects spanning target discovery, mechanistic studies, and early-stage therapeutic development.

DPhil projects available 

Reilly Group: Targeting adverse myocardial remodelling in atrial fibrillation and cardiac fibrosis — Radcliffe Department of Medicine