Research Interests
Intestinal hormone secretion and action
The intestine secretes approximately 20 different hormones from enteroendocrine cells (EECs), found scattered throughout the intestinal epithelium. Several secreted peptide hormones have important regulatory roles for metabolism; glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) for example boost postprandial insulin secretion and modulate food intake and their receptors are the target for drugs now widely used to treat diabetes and obesity. Based on their success many other gut hormones and their receptors are currently investigated for their therapeutic potentials
Our lab, which works in close collaboration with Fiona Gribble’s group, characterises the stimulus secretion coupling in EECs aiming to find ways to modulate release of endogenous hormone pools – in the context of obesity and diabetes we would like to boost secretion of incretins (GLP-1, GIP) and/or other anorexic hormones such as peptideYY (PYY), cholecystokinin (CCK), whereas we would like to inhibit the release of Insulin-like peptide-5 (Insl5), as elevated levels of this hormone are found in bile acid-and irritable bowel syndrome with diarrhoea. Expressing fluorescent indicators in specific EECs in human or mouse derived intestinal organoids allows us to monitor acute responses to potential stimuli. We are using similar techniques in mice to selectively monitor (in vivo fibre photometry) or manipulate (chemo- or optogenetically) EEC-hormone receptor expressing cells, with a current focus on GIP-receptor expressing cells in the CNS involved in the food intake modulation of GIPR-agonists and antagonists. With Richard Kay we are developing LC-MS/MS based methods for simultaneous and sensitive detection of gut hormones in biological matrices, which we hope will extend our understanding of integrated EEC-responses to different nutrient challenges and after intestinal surgery.
Group Members (all joint with Gribble)
Constanza Alcaino, Research Associate - caa62 at medschl.cam.ac.uk
Sofia Aleksashina, PhD student - sa2115 at medschl.cam.ac.uk
Chris Bannon, Clinical Research Associate - camb3 at medschl.cam.ac.uk
Adam Davison, Research Associate - ad2256 at cam.ac.uk
Htar Htar Hlaing, Clinical Research Associate - hhh32 at cam.ac.uk
Paula-Peace James-Okoro, PhD student - ppoj2 at medschl.cam.ac.uk
Richard Kay, Senior Research Associate - rgk27 at medschl.cam.ac.uk
Jo Lewis, Research Associate - jl2033 at medschl.cam.ac.uk
Tianyi Lu, PhD student - tl602 at cam.ac.uk
Mireia Montaner - Research Associate - mm2727 at medschl.cam.ac.uk
Danae Nuzzaci, Research Associate - dn371 at medschl.cam.ac.uk
Haruhiko Omori, PhD Student - ho322 at cam.ac.uk
Akhila Palakodaty, PhD Student - asp66 at cam.ac.uk
Varsha Pramod Rao, Research Assistant - vp442 at cam.ac.uk
Marta Santos Hernandez, Research Associate - ms2896 at medschl.cam.ac.uk
Christopher Smith, Research Associate - cas228 at medschl.cam.ac.uk
Mae Tabbada, PhD student - jmt97 at cam.ac.uk
Research Funding
Medical Research Council (MRC)
Biotechnology and Biological Sciences Research Council (BBSRC)
National Institute for Health Research – Biomedical Research Centre (NIHR-BRC)
