Cardiovascular Research Centre

Staff Profile

Dr Gavin Richardson

Newcastle Uni Research Fellow (Cardio)

Background

https://f1000.com/prime/735057071?subscriptioncode=2baed234-c837-4cbc-b801-22771ddb2953&utm_medium=email&utm_source=prime_ypp

I have a long-standing interest in regenerative biology and have worked on both embryonic stem cells and adult stem cell populations in different tissues, including heart, skin and hair follicles. I am fortunate to have had the opportunity to work at a number of leading institutions including Durham University and Newcastle University in the UK, and Columbia and Harvard Universities in the USA. Since moving to Newcastle University in 2010, I have focussed my research on myocardial senescence and regeneration, as this exciting research field has great potential to improve the quality of life of many individuals suffering from heart failure. 

Area of Expertise

Myocardial senescence, regeneration and ageing. 

Our research goal is to understand how senescence and attenuated regenerative capacity contribute to the pathophysiology of cardiovascular diseases which can lead to heart failure. Our data suggest cellular senescence accumulates during ageing or as a result of myocardial infarction. Through the production of a senescence-associated secretory phenotype (SASP), which is pro-senescent, pro-fibrotic and pro-hypertrophic, senescent cells promote adverse myocardial remodelling and attenuate regenerative potential. This ultimately impairs cardiac function. We have demonstrated that the elimination of senescence, and the SASP, attenuates remodelling and improves cardiac function. We suggest that targeting senescence and the SASP therapeutic in patients will slow or stop disease progression and improve cardiac function. Our ongoing projects aim to further understand the mechanisms that drive senescence during cardiovascular disease and characterise the SASP proteins that contribute to myocardial remodelling. This will enable us to identify novel therapeutics for patients.

Collaborator BHF Regenerative Medicine Centres. http://www.imperial.ac.uk/bhf-research-excellence

Current Funding

2019: Senescence as a potential therapeutic target for ischaemic reperfusion injury following acute myocardial infarction - British Heart Foundation project Grant PG/19/15/34269. https://www.bhf.org.uk/research-projects/2019/04/30/08/23/senescence-as-a-potential-therapeutic-target-for-ischaemia-reperfusion-injury-following-acute-myocar

2019: Non-invasive, repeatable measurements of cardiac function to evaluate therapeutics for aged related cardiac dysfunction. https://www.ncl.ac.uk/medicalsciences/research/wellcome/#smallgrantsscheme

2019: The effect of irrigation rate on optimal radiofrequency ablation lesion formation. Boston Scientific.

2019: Non-invasive, repeatable measurements of cardiac function to evaluate therapeutics for aged related cardiac dysfunction. The Wellcome Trust Institutional Strategic Support Fund. https://www.ncl.ac.uk/medicalsciences/research/wellcome/#smallgrantsscheme

2018: Senescence as a potential therapeutic target for aged related cardiac dysfunction - Newcastle upon Tyne Hospitals NHS Charity Project grant.  http://www.newcastle-hospitals.org.uk/about-us/research-and-newcastle-hospitals_charity-support.aspx

2018: Cardiomyocyte senescence and the bystander effect in human myocardial ageing. The Wellcome Trust Institutional Strategic Support Fund. https://www.ncl.ac.uk/medicalsciences/research/wellcome/#smallgrantsscheme

2017:  Impact of duration of idiopathic dilated cardiomyopathy on patient-derived native cardiac stem cells - Newcastle upon Tyne Hospitals NHS Charity Project grant. Co-I, PI Dr Annette Messon. http://www.newcastle-hospitals.org.uk/about-us/research-and-newcastle-hospitals_charity-support.aspx

2016: The role of cardiomyocyte senescence and cardiac regeneration ischemia-reperfusion injury.Newcastle Research Excellence Academy PhD studentship. https://www.ncl.ac.uk

2016: Could a senescence host microenvironment be detrimental to cellular therapy?- BHF Centre for Regenerative Medicine Pilot Granthttps://www.bhf.org.uk/what-we-do/our-research/mending-broken-hearts/research/centres-of-regenerative-medicine

2016: The role of cardiomyocyte senescence and cardiac regeneration in ageing - British Heart Foundation project Grant PG/15/85/31744. https://www.bhf.org.uk/research-projects/the-role-of-cardiomyocyte-senescence-and-cardiac-regeneration-in-ageing

2014: Cardiomyocyte regeneration in non-ischaemic cardiomyopathy- British Heart Foundation project Grant- PG/13/69/3054. https://www.bhf.org.uk/research-projects/cardiomyocyte-regeneration-in-nonischaemic-cardiomyopathy.

Google Scholar

SCOPUS

Orcid

Research

Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Rather than replace lost myocardium, cardiovascular diseases such as myocardial infarction (MI), myocarditis, idiopathic or hereditary cardiomyopathy are associated with adverse myocardial remodelling and ventricular dilation, with a progression from asymptomatic to symptomatic HF. The apparent lack of regeneration following cardiomyocyte loss resulted in the view that the heart is a post-mitotic organ. Recently this hypothesis has been refuted; a number of groups have demonstrated that following acute ischaemic injury the heart responds with an increase in cardiomyocyte generation, and we have also published novel data demonstrating cardiomyocyte regeneration also occurs in response to cardiomyocyte loss as a result of chronic non-ischaemic cardiomyopathy. These studies provide strong evidence that regardless of disease aetiology the heart has limited but measurable endogenous regenerative potential and raise questions regarding the contribution of regenerative dysfunction in the pathophysiology of heart failure. Moreover, it raises the exciting possibility that this innate regenerative potential could be enhanced therapeutically to benefit the many individuals suffering from HF.

Myocardial Ageing and Regeneration

Ageing is the biggest risk factor for impaired cardiovascular health and is associated not only with an increased prevalence of cardiovascular disease but also a poorer prognosis. In our recently published work, we have demonstrated that in mice cardiomyocyte turnover declines with age and we hypothesize that an impaired regenerative potential contributes to both a decline in cardiac function with age and poorer outcomes in the elderly following MI. We have therefore begun to investigate the mechanisms that may underlie attenuated cardiomyocyte regeneration. 

Myocardial Senescence and Revitalisation

Cellular senescence is defined as the irreversible loss of division potential in somatic cells. While senescence can be a potent anti-tumour mechanism recent studies have indicated that it is a major contributor to age-dependent tissue dysfunction.  We have demonstrated that within the cardiomyocyte population there is an age-dependent increase in senescence which contributes to impaired regenerative potential and myocardial remodelling. We are now testing the potential of targeting this senescent cell population in order to revitalise the myocardium in aged and diseased hearts. 

Teaching

PSC2020 – Cardiovascular System Physiology

The heart as a regenerative organ

This lecture will introduce the heart as a regenerative organ and outline the cellular mechanisms controlling cardiomyocyte regeneration.  This will include descriptions of the studies that first demonstrated cardiomyocyte regeneration occurs in humans and the subsequent studies that used complex transgenic lineage mouse models to identify the source of this regenerative potential.  Consideration will be given to how these studies influence our interpretation of ongoing human trials in regenerative medicine.

Myocardial ageing, regeneration and senescence

This lecture will introduce cellular senescence and the relatively new concept that senescence in the myocardium may contribute to cardiac ageing and age-related dysfunction.  Attention will be given to how senescence contributes to attenuation in cardiomyocyte regenerative potential.  Consideration will be given to the influence of age on outcome and recovery to myocardial infarction.

Publications