Research Interests:
My broad aim is to identify how the mammalian brain represents internal nutrient and energy availability and orchestrates behavioural, metabolic and endocrine responses for nutritional homeostasis.
Theme 1: Brain nutrient sensing for amino acid homeostasis:
Half of the amino acids cannot be synthesized by mammalian cells and must be obtained through the diet. A shortage of these essential amino acids rapidly drives protein hunger, yet high circulating levels of amino acids is toxic, leading to metabolic and neurological diseases.
We work under the hypothesis that homeostatic mechanisms regulate peripheral amino acid availability to maintain nutritional balance and ensure survival. Impairments in these pathways contribute to the pathophysiology of obesity and metabolic diseases, but little is known about how this is achieved.
Our goal is to understand how the mammalian brain senses peripheral amino acid availability and produces behavioural and metabolic responses that maintain amino acid homeostasis, and how this regulation is integrated with or might conflict with the maintenance of energy homeostasis. Eventually our goal is to determine if brain protein-sensing pathways represent effective targets for weight-loss interventions and restoring metabolic health.
Theme 2: Nutrient sensing in oligodendrocytes
Oligodendrocytes are myelin-forming cells that ensheathe axons to allow rapid saltatory conduction of action potentials. While oligodendrocytes are typically long-lived in a healthy brain, we have found that they rapidly turnover in the median eminence—the brain region through which hypothalamic neurons access blood signals—leading to rapid myelin renewal. This plasticity is regulated by nutritional and metabolic cues. We are actively working on identifying the functional significance of median eminence oligodendrocyte and myelin turnover in neuroendocrine functions and energy and glucose homeostasis.
Theme 3: Targeting brain nutrient sensing for weight loss
Our third goal is to identify the mechanism of action of GLP-1 based weight-loss drugs.
Group Members:
Dr Thomas Brown, Research Associate - tb807 at medschl.cam.ac.uk
Dr Anthony Tsang, Research Associate - at783 at medschl.cam.ac.uk
