Research Aims & Objectives
Cardiovascular development and regeneration
We seek to:
- understand the cellular and molecular pathways underpinning normal heart development to model congenital heart disease
- extrapolate to reactivate embryonic programmes in endogenous adult cells to restore lost tissue after a heart attack
- to condition the local injury environment to optimise repair and regeneration and prevent heart failure
Details of research interests
We study cardiovascular development to understand the basis of congenital heart disease and to inform on potential strategies to target heart regeneration after a “heart attack”. We combine insights gained from zebrafish and mouse models with human studies to identify evolutionary conserved cellular and molecular pathways that underpin normal development and may act as therapeutic targets to repair and regenerate the injured or diseased adult heart.
Combining studies on model organisms that can inherently regenerate their hearts after injury, such as adult zebrafish and neonatal mice, provides a platform for extrapolating our findings to human heart attack patients with the ultimate goal to restore normal heart function and prevent the onset of heart failure.
Our studies on heart development focus on key lineages, including the epicardium, lymphatic vasculature and tissue resident macrophages. We are part of a Wellcome-funded Human Developmental Biology Initiative (HDBI) which seeks to gain fundamental insights into human development. Our focus is on cell lineage contributions to the early forming human heart and key morphogenetic events (outflow tract formation and septation of the chambers) which are implicated in congenital heart disease.
To extrapolate to heart regeneration, we aim to understand how to reactivate embryonic programmes in key adult cell types, enabling us to restore cardiovascular tissues. Two embryonic processes we study in this regard are epicardial cell activation (so-called epithelial-to-mesenchyme transition) and lymphatic vessel growth and sprouting (termed lymphangiogenesis). These are targets for ongoing small molecule drug-discovery, combining human cell-based screens, automated imaging, machine learning and medicinal chemistry. In parallel, we study how to condition the local injury environment to provide an optimal setting in which to restore lost cardiovascular tissues. Here we are targeting modulation of the immune response (immunomodulation) and reduced scarring of the heart (anti-fibrosis) both during the initial (acute) stages of injury and longer term to prevent complications associated with (chronic) heart failure.
Paul R. Riley
- Dr Susanna Cooper
- Dr Claudio Cortes Rodriguez
- Dr Elisabetta Gamen
- Dr Adam Lokman
- Dr Daniela Pezzolla
- Dr Christophe Ravaud
- Dr Xin Sun
- Dr Michael Weinberger
- Carolina Roque Silva
- Sarah Sigal
- Alexa Cosma
- Denise Lynch (laboratory manager)
- Emma Philipson (personal assistant)
- Tertia Softley (BHF centre manager)
Collaborators - Oxford:
Collaborators - External:
- Karl Kaddler, University of Manchester
- Manuel Mayr, Kings College London
- Nadia Rosenthal, The Jackson Laboratory, Bar Harbor, US
- British Heart Foundation
- Chan-Zuckerberg Initiative
- Medical Research Council
We have an extensive track record of public engagement via media articles, interviews, blogs, podcasts, television and radio appearances; school and higher education visits and public lectures: links. We publicise our research using multiple media forums including Twitter (@GroupRiley) and public speaking opportunities to disseminate our findings to non-expert audiences. We present our work at the Cheltenham and Oxford annual science festivals (scheduled for June and October each year, respectively) and at Pint of Science, to engage individuals who have a vested interest in understanding the impact of cardiovascular disease (patients and relatives). We present at school and college open days, to engage the next generation of young scientists, and we are happy to host sixth form students and undergraduates for internships to offer experience of academic research and provide insight into research career opportunities.