Metabolic Crosstalk

Biography 

I completed a BSc in Neuroscience at the University of Leeds and then an MSc in Neuroscience at University College London. I next undertook a PhD in Metabolism at Imperial College London during which I characterised novel gut hormone analogues for weight loss and their central mechanisms of action. This was followed by postdoctoral appointments at the University of Oxford, University of Leipzig, University Hospital Wuerzburg and the University of Zurich.  

Over my career, I have developed a research identity on gut-brain communication, adipose tissue thermogenesis and the gut barrier, and how these are modified by Roux-en-Y gastric bypass surgery (RYGB). I have presented at international conferences throughout the world and have published research and review articles in prestigious journals including Cell Metabolism, Trends in Endocrinology and Metabolism, EMBO Reports, EMBO Molecular Medicine, the Journal of Nuclear Medicine and JCI Insight.  

Research Interests 

My lab is interested in studying interventions that promote metabolic health at the molecular, cellular and systems levels of mechanistic detail. These interventions include, but are not limited to, lifestyle modifications such as exercise and diet, surgical procedures such as RYGB and pharmacological treatments such as semaglutide (Ozempic). Particular emphasis is placed on changes in metabolic crosstalk caused by these interventions, as well as how the interindividual variability in their outcomes is shaped by genetic, epigenetic, gut microbiota and sex factors. 
 
A major focus of the lab is on how RYGB not only promotes healthier eating behaviour and weight loss but also improvements in glycaemic control and amelioration of fatty liver. For example, I have previously shown that these effects of RYGB could be due to the increased release of metabolically beneficial cytokines such as GDF15 and Il-22 from the reconfigured gut. Physiologically, GDF15 is released from stressed cells (such as enterocytes) and suppresses food intake via a caudal hindbrain pathway, while Il-22 is released from activated immune cells (such as type 3 innate lymphoid cells) by microbial metabolites and improves insulin sensitivity. We intend to study these and similar processes in the context of RYGB in more mechanistic detail using a variety of molecular biology, cell biology and in vivo techniques in both preclinical models and patient samples. Ultimately, using this approach we hope to inform the development of pharmacological treatments that recapitulate the metabolic benefits of RYGB.  

Another focus of the lab is on novel stimulators of adipose tissue thermogenesis, and how these can be harnessed to promote metabolic health. For example, I have previously shown using positron emission tomography imaging that the dual-specificity phosphodiesterase PDE10A is expressed in murine and human adipose tissue, and that its inhibition stimulates adipose tissue thermogenesis and causes weight loss in association with improved insulin sensitivity in diet-induced obese mice. We intend to study the function of PDE10A and similar signalling molecules in adipocytes in more mechanistic detail again using a variety of molecular biology, cell biology and in vivo techniques in both preclinical models and patient samples.