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Institute of Metabolic Science

Metabolic Research Laboratories
 

Research Interests 

Hormones from the gut are central to the control of appetite and insulin release. Drugs based on the gut hormone glucagon-like peptide-1 (GLP-1) have proved highly successful for treating type 2 diabetes, and suppressing food intake. In collaboration with Frank Reimann our group researches how gut hormones are released and their actions on target tissues. We hope this will lead to the development of new drugs or diets that treat diabetes and obesity by targeting gut hormone release. 

The release of gut hormones such as GLP-1 and PYY after a meal conveys signals to the brain to stop eating, to the pancreas to produce insulin and to the gut to coordinate digestion. We are particularly interested in establishing how gut hormones are released after food ingestion, and how the gut endocrine system is affected after gastric bypass surgery. 

Our research encompasses a range of experimental approaches, from physiological studies in humans and mouse models to analysis of single cells in vitro. We use optical and electrophysiological recording techniques to monitor stimulus detection and vesicle release from cells in intestinal organoids, tissue slices and immortalized cell lines. We have generated transgenic murine models and human intestinal organoids in which cells of interest (enteroendocrine cells or cellular targets of gut hormones) are labelled by cell-specific fluorescent markers and reporters of cytoplasmic signalling pathways, or harbour genetic deletions of genes of interest. The mechanisms by which cells detect stimuli are identified by combining methods such as live cell imaging of second messenger pathways, electrophysiology, transcriptomics and measurements of hormone secretion using immunoassays and LC-MS.  

In clinical studies, we are interested in how nutrition affects patterns of postprandial gut hormones, and the potential impact on food intake and glucose homeostasis, as well as gut hormone disturbances in conditions such as bile acid diarrhoea and IBS.   


PhD opportunity 2025-2029

Role of gut bitter taste receptors in enteroendocrine and epithelial signalling

Cambridge supervisors: Professors Fiona Gribble and Frank Reimann; GSK supervisor: Dr Konstantinos Stamatopoulos

This is a 4 year studentship, hosted in the Institute of Metabolic Science-Metabolic Research Laboratories in partnership with GSK. It is fully funded by GSK and will cover stipend, consumables and fees for UK based and overseas candidates. The project aims to identify the cellular and molecular targets of bitter chemicals in the gut, testing the hypothesis that activation of bitter taste receptors occurs in chemosensory enteroendocrine cells and/or other secretory cells (e.g. Paneth, Goblet or Tuft cells), with downstream effects on absorptive cells mediated by paracrine signalling.

Further details


Group Members (all joint with Reimann) 

Constanza Alcaino, Research Associate  - caa62@medschl.cam.ac.uk 

Sofia Aleksashina, PhD student - sa2115@medschl.cam.ac.uk 

Chris Bannon, Clinical Research Associate - camb3@medschl.cam.ac.uk 

Sijing Cheng, Research Associate - sc2470@medschl.cam.ac.uk 

Adam Davison, Research Associate - ad2256@cam.ac.uk 

Gabriela Gil, Research Assistant - gg550@cam.ac.uk 

Htar Htar Hlaing, Clinical Research Associate - hhh32@cam.ac.uk 

Paula-Peace James-Okoro, PhD student - ppoj2@medschl.cam.ac.uk 

Richard Kay, Senior Research Associate - rgk27@medschl.cam.ac.uk  

Jo Lewis, Research Associate - jl2033@medschl.cam.ac.uk  

Tianyi Lu, MPhil student - tl602@cam.ac.uk 

Mireia Montana - mm2727@medschl.cam.ac.uk 

Danae Nuzzaci, Research Associate - dn371@medschl.cam.ac.uk 

Austin Punnoose, Research Assistant in the Mass Spectrometry Core - Avp34@medschl.cam.ac.uk 

Marta Santos Hernandez, Visiting Post-doctoral Fellow  - ms2896@medschl.cam.ac.uk 

Christopher Smith, Research Associate - cas228@medschl.cam.ac.uk  

Mae Tabbada, PhD student - jmt97@cam.ac.uk 


Research Funding 

Wellcome 

Medical Research Council (MRC) 

Biotechnology and Biological Sciences Research Council (BBSRC) 

National Institute for Health Research – Biomedical Research Centre (NIHR-BRC) 

Publications

Key publications: 

Lewis JE, Nuzzaci D, James-Okoro PP, Montaner M, O'Flaherty E, Darwish T, Hayashi M, Liberles SD, Hornigold D, Naylor J, Baker D, Gribble FM, Reimann F. Stimulating intestinal GIP release reduces food intake and body weight in mice. Mol Metab. 2024 Jun;84:101945. doi: 10.1016/j.molmet.2024.101945. PMID: 3865340 

Foreman RE, Miedzybrodzka EL, Eiríksson FF, Thorsteinsdóttir M, Bannon C, Wheller R, Reimann F, Gribble FM, Kay RG. Optimized LC-MS/MS Method for the Detection of ppCCK(21-44): A Surrogate to Monitor Human Cholecystokinin Secretion. J Proteome Res. 2023 Sep 1;22(9):2950-2958. doi: 10.1021/acs.jproteome.3c00272. PMID: 37591880 

Lewis JE, Woodward OR, Nuzzaci D, Smith CA, Adriaenssens AE, Billing L, Brighton C, Phillips BU, Tadross JA, Kinston SJ, Ciabatti E, Göttgens B, Tripodi M, Hornigold D, Baker D, Gribble FM, Reimann F. Relaxin/insulin-like family peptide receptor 4 (Rxfp4) expressing hypothalamic neurons modulate food intake and preference in mice. Mol Metab. 2022 Dec;66:101604. doi: 10.1016/j.molmet.2022.101604 PMID: 36184065 

Galvin SG, Kay RG, Foreman R, Larraufie P, Meek CL, Biggs E, Ravn P, Jermutus L, Reimann F, Gribble FM. The Human and Mouse Islet Peptidome: Effects of Obesity and Type 2 Diabetes, and Assessment of Intraislet Production of Glucagon-like Peptide-1. J Proteome Res. 2021 Sep 3;20(9):4507-4517. doi: 10.1021/acs.jproteome.1c00463. Epub 2021 Aug 23. PMID: 34423991 PMCID:PMC8419866 

Yang M, Darwish T, Larraufie P, Rimmington D, Cimino I, Goldspink DA, Jenkins B, Koulman A, Brighton CA, Ma M, Lam BYH, Coll AP, O’Rahilly S, Reimann F, Gribble FM. Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells. Sci Rep. 2021 Jan 28;11(1):2529. doi: 10.1038/s41598-021-81349-7. PMID: 33510216PMCID: PMC7843649 

Goldspink DA, Lu VB, Miedzybrodzka EL, Smith CA, Foreman RE, Billing LJ, Kay RG, Reimann F, Gribble FM. Labeling and Characterization of Human GLP-1-Secreting L-cells in Primary Ileal Organoid Culture. Cell Rep. 2020 Jun 30;31(13):107833. doi: 10.1016/j.celrep.2020.107833. PMID: 32610134. PMCID: PMC7342002 

Lewis JE, Miedzybrodzka EL, Foreman RE, Woodward ORM, Kay RG, Goldspink DA, Gribble FM, Reimann F. Selective stimulation of colonic L cells improves metabolic outcomes in mice. Diabetologia. 2020 Jul;63(7):1396-1407. doi: 10.1007/s00125-020-05149-w. Epub 2020 Apr 27. PMID: 32342115. PMCID: PMC7286941 

Adriaenssens AE, Biggs EK, Darwish T, Tadross J, Sukthankar T, Girish M, Polex-Wolf J, Lam BY, Zvetkova I, Pan W, Chiarugi D, Yeo GSH, Blouet C, Gribble FM, Reimann F. Glucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 30(5):987-996 PMID:31447324, PMCID: PMC6838660 

Professor of Endocrine Physiology
Honorary Consultant in Clinical Biochemistry
Director of Graduate Education for the School of Clinical Medicine
Deputy Director of the Metabolic Research Laboratories

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