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Institute of Metabolic Science

Metabolic Research Laboratories
 

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 

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: 

Bannon CA,  Walters JRF,  Wu T, Kay R , Punnoose A, Spiller R, Wilson J, Verdino P, Barker P , Burling K, Horowitz M, Rayner CK, Ford AC, *Reimann F, *Gribble FM (2025) Insulin like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea. Gut. 2025 Jul 23:gutjnl-2025-335393. doi: 10.1136/gutjnl-2025-335393. Online ahead of print. PMID: 40701790 (* joint corresponding)

Alcaino C, Guccio N, Miedzybrodzka EL, Quale JR, Lu T, Davison A, Smith CA, Overington E, Santos- Hernández M, Tabbada M, Hodge M, Bany-Bakar R, Kay R, Shaaban A, *Imig C, *Reimann F, Gribble FM (2025) Mechanisms of Activation and Serotonin release from Human Enterochromaffin Cells. Cell Mol Gastroenterol Hepatol. 2025 Aug 13:101610. doi: 10.1016/j.jcmgh.2025.101610. Online ahead of print. PMID: 40812684  (* joint corresponding)

Guccio N, Alcaino C, Miedzybrodzka EL, Santos-Hernández M, Smith CA, Davison A, Bany Bakar R, Kay RG, *Reimann F, *Gribble FM (2024) Molecular mechanisms underlying Glucose-dependent insulinotropic polypeptide secretion in human duodenal organoids. Diabetologia. 2025 Jan;68(1):217-230. doi: 10.1007/s00125-024-06293-3. Epub 2024 Oct 23. PMID: 39441374 PMCID: PMC11663192 (* joint corresponding)

Smith CA, O’Flaherty EAA, Guccio N, Punnoose A, Darwish T, Lewis JE, Foreman RE,  Li J, Kay RG, Adriaenssens AE, *Reimann F, *Gribble FM (2024) Single-cell transcriptomic atlas of enteroendocrine cells along the murine gastrointestinal tract. PLoS One. 2024 Oct 8;19(10):e0308942. doi: 10.1371/journal.pone.0308942. eCollection 2024. PMID: 39378212 PMCID: PMC11460673 (* joint corresponding)

Xu Y, Michalowski CB, Koehler J, Darwish T, Guccio N, Alcaino C, Domingues I, Zhang W, Marotti V, Van Hul M, Paone P, Koutsoviti M, Boyd BJ, Drucker DJ, Cani PD, *Reimann F, *Gribble FM, *Beloqui A (2024) Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion. Sci Adv. 2024 Dec 13;10(50):eadq9909. doi: 10.1126/sciadv.adq9909. Epub 2024 Dec 13. PMID: 39671480 PMCID: PMC11641013 (* joint corresponding)

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. (2024) 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, Bannon CA, *Kay RG, *Reimann F, *Gribble FM (2024) Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry. Front Endocrinol (Lausanne). 2024 Mar 13;15:1348146. doi: 10.3389/fendo.2024.1348146. eCollection 2024. PMID: 38544692 PMCID: PMC10965782 (* joint corresponding)

Foreman RE, Miedzybrodzka EL, Eiríksson FF, Thorsteinsdóttir M, Bannon C, Wheller R, Reimann F, Gribble FM, Kay RG. (2023) 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 

*Adriaenssens A, Broichhagen J, de Bray A, Ast J, Hasib A, Jones B, Tomas A, Figueredo Burgos N, Woodward O, Lewis J, O’Flaherty Rottenberger E, El K, Cui C, Harada N, Inagaki N, Campbell J, Brierley D, Hodson D, Samms R, *Gribble F, *Reimann F (2023) Glucose-dependent insulinotropic polypeptide receptor (GIPR)-expressing neurons in the hypothalamus and the dorsal vagal complex employ distinct mechanisms to affect feeding behaviour. JCI Insight. 2023;8(10):e164921. PMID: 37212283 doi.org/10.1172/jci.insight.164921  

*Lewis JE, Woodward ORM,  Nuzzaci D, Smith CA, Adriaenssens AE, Billing L, Brighton C, Phillips BU, Tadross JA, Kinston SJ, Ciabatti E, Göttgens B, Tripodi M, Hornigold D, David Baker D, *Gribble FM, *Reimann F (2022) Relaxin/insulin-like family peptide receptor 4 (Rxfp4) expressing hypothalamic neurons modulate food intake and preference in mice. Mol Metab 2022 Sep 30;66:101604. doi: 10.1016/j.molmet.2022.101604. PMID: 36184065 (* joint corresponding) 

Professor of Endocrine Signalling
Department of Clinical Biochemistry

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