CoRE-funded Researcher: Dr James Minchin

CoRE-funded Researcher: Dr James Minchin

James is originally from Bath and obtained his PhD in 2010 from King’s College London. James then joined the laboratory of Dr. John Rawls at Duke University for postdoctoral training, before joining CVS as an EPICT fellow, funded by the BHF CoRE, in Summer 2016. Whilst a postdoc in the Rawls lab, James started to explore the utility of using zebrafish to study adipose tissues – specialized organs that accumulate fat, which are massively enlarged and dysfunctional in obesity. In particular, James was drawn to the zebrafish model for two principal reasons; the ability to visualize adipose tissue non-invasively and in live animals, and the ability to conduct large-scale screens to identify new therapeutic candidates for treating some of the symptoms associated with obesity. In addition to these advantages, previous research has shown that zebrafish adipose tissue is highly conserved to mammalian adipose, suggesting that research findings can be translated to humans.

At CVS, James is applying research using the zebrafish model system to help understand how genetics can influence body fat distribution and susceptibility to cardiovascular disease and diabetes. This is an important biomedical question, as greater accumulation of adipose tissue around the waist increases disease risk; whereas, accumulation of adipose around the hips is metabolically beneficial. However, factors that regulate the balance between ‘good fat’ and ‘bad fat’ are largely unknown. An individual’s body fat distribution is inherited from their parents, which suggests a strong genetic influence, and in the past few years, genome-wide association studies (GWAS) have identified regions of the genome that contribute to body fat distribution and disease susceptibility. Precise biological mechanisms that underlie these genetic associations are unknown, and the goal of James’ research is to elucidate and exploit these mechanisms to transform ‘bad fat’ into ‘good fat’.

Recently, James used fluorescent dyes to visualize the distribution of fat in live zebrafish, and analyzed the function of candidate genes at GWAS loci for effects on body fat distribution. Using zebrafish, James found that Plexin D1 (PLXND1) – a gene involved in new blood vessel formation - regulated body fat distribution and induced metabolic parameters seen during early stages of diabetes progression. These findings were followed up in humans, where similar associations between PLXND1, body fat distribution and diabetes were observed in patients, suggesting that PLXND1 may be targeted to alleviate some of the metabolic disruptions that occur in patients with high adiposity around the waist.