Understanding how energy balance regulates human endocrine and immune function.
Research Vision
I am currently a Clinical Lecturer in Metabolic Medicine. My aim is to understand the consequences of disordered energy balance on hormone regulation and immune function to improve treatment for people with obesity. My research focuses on two main areas:
1) Neuroendocrine dysfunction in obesity
The neural and molecular mechanisms mediating the effects of obesity on hormone dysfunction are incompletely understood. Both underweight and obesity lead to changes in neuroendocrine hormones such as male and female hormones, growth hormone and thyroid hormones. These hormones control fertility, growth, bone structure, heart function and metabolism.
During my Wellcome Postdoctoral Fellowship, I demonstrated how two groups of genes regulate both energy balance and endocrine function. In collaborative studies, combining human genetics, cellular work and studies in animals and humans, we found that the Semaphorin3-Neuropilin-PlexinA (S3NPA) family of genes control hypothalamic development and that the transcription factor Steroid Receptor Coactivator-1 (SRC-1) modulates the expression of POMC and electrical activity of POMC neurons to cause obesity. These findings provided the rationale for people with severe obesity who harbour these variants to be offered treatment with a melanocortin receptor agonist in clinical trials. In going studies, I am using brain imaging and computational techniques to map neural networks within and from the hypothalamus in humans.
2) Immune dysfunction in disordered energy balance
Obesity leads to more frequent and severe infections, which became poignantly visible during the COVID-19 pandemic. However, immune dysfunction in obesity is poorly understood and understudied. Treatment and clinical outcomes of (severe) infections in people with obesity may be improved by understanding the underlying processes that drive immune dysfunction.
As co-PI on the UKRI-funded SCORPIO (Sars-Cov-2 vaccine ResPonse in Obesity), I am leading clinical studies into the immune response to SARS-CoV-2 vaccines in obesity with colleagues at the MRC Toxicology Unit (Dr James Thaventhiran), Department of Medicine (Dr Nicholas Mattheson) and Babraham Institute (Dr Michelle Linterman) and IMS (Prof Sadaf Farooqi) (https://scorpiostudy.org.uk/).
Furthermore, I am studying T and B cell function in people with genetic variants in SRC-1 and S3NPA family of genes to investigate how these specific molecular pathways regulate both nutrition and immunity in humans.
