Dr Caroline Gorvin

Department of Metabolism and Systems Science
Sir Henry Dale Fellow
Associate Professor of Receptor Biology

Contact details

Telephone: +44 (0)121 414 6857
Email: c.gorvin@bham.ac.uk
Twitter: @caroline_gorvin

Address: University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Caroline’s research is focussed on the trafficking and signalling of membrane proteins, and how their impairments contribute to endocrine and metabolic disease. Her research group investigates the fundamental mechanisms by which G protein-coupled receptors signal to regulate appetite, bone metabolism and calcium homeostasis.

Qualifications

DPhil in Clinical Medicine, University of Oxford, 2012.
BSc (Hons) in Biomedical Science with Industrial Experience, University of Manchester, 2008.

Biography

Caroline obtained her BSc (Hons) in Biomedical Science with Industrial Experience in 2008 from the University of Manchester. She spent her year in industry at AstraZeneca plc in the in vitro electrophysiology team. Caroline then moved to the University of Oxford for her PhD studies, where her research focussed on the cellular mechanisms by which mutations in a chloride-proton antiporter cause the renal disorder Dent’s disease. She also spent time on secondment at UMC St Radboud, Nijmegen, The Netherlands, during this period.

Caroline continued in Oxford undertaking postdoctoral research investigating the signalling and trafficking of the GPCR, calcium-sensing receptor, and its role in calcium homeostasis. She moved to Birmingham in January 2018 to establish her research group. Caroline’s research group has active research programmes investigating:

Signalling of GPCRs involved in appetite regulation (funded by a Wellcome Trust & Royal Society Sir Henry Dale Fellowship),

How genetic alterations in the calcium-sensing receptor, and components of its signalling pathway, contribute to human disorders of calcium homeostasis.

She has recently completed a research secondment at Weill Cornell Medicine and Queen Mary University of London.

Research

Caroline collaborates with both basic science researchers and clinicians to advance understanding of GPCR signalling in endocrine and metabolic disease. These encompass two main themes.

Signalling of GPCRs involved in appetite regulation

The Gorvin group investigates fundamental mechanisms by which metabolic GPCRs signal within cells. Studies include: understanding how accessory proteins interact with GPCRs to modify their signalling and internalisation; and investigating how receptor dimerisation and cross-talk influence signal dynamics.

Calcium-sensing receptor signalling & trafficking

Dr Gorvin has expertise in calcium-sensing receptor (CaSR) signalling and the contribution of receptor mutations to disorders of calcium homeostasis. Her research has: defined new paradigms for CaSR signalling by spatiotemporal G-protein pathways; described new disease-biased CaSR signalling pathways; repurposed allosteric modulators for patients with hyper/hypocalcaemia; and contributed to informing clinical guidelines for genetic testing in hypercalcaemia.

This research combines microscopy techniques (including single molecule imaging) with signalling assays (e.g. BRET, HTRF, TR-FRET, AlphaScreen and reporter assays) in primary and immortalised cell-lines. The Gorvin group is happy to provide expertise and collaborate with any researchers that have an interest in membrane proteins, cell signalling or trafficking.

Current group members

Aqfan Jamaluddin (Post-doc)
Rachael Wyatt (Research Technician)
Holly Brittain (MRC DTP, PhD Metabolism and Systems Research)

Other activities

Member of the MRC IAA Management Group.
Member of the Science Committee for the Society for Endocrinology.
Member of the Leadership and Development Awards Selection Panel for the Society for Endocrinology.
Editorial board membership for Journal of Endocrinology, Journal of Molecular Endocrinology, Journal of the Endocrine Society.
Organise seminar series for the Department of Metabolism & Systems Science (MSS) and the Centre of Membrane Proteins & Receptors (COMPARE).

Publications

Jamaluddin A, Wyatt RA, Broichhagen J, Levitz J, Gorvin CM. MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants. Cell Rep. 2026. 45(3):117018. doi:10.1016/j.celrep.2026.117018.

Wallis NJ, McClellan A, Mörseburg A, Kentistou KA, Jamaluddin A, Dowsett GKC, Schofield E, Morros-Nuevo A, Saeed S, Lam BYH, Sumanasekera NT, Chan J, Kumar SS, Zhang RM, Wainwright JF, Dittmann M, Lakatos G, Rainbow K, Withers D, Bounds R, Ma M, German AJ, Ladlow J, Sargan D, Froguel P, Farooqi IS, Ong KK, Yeo GSH, Tadross JA, Perry JRB, Gorvin CM, Raffan E. Canine genome-wide association study identifies DENND1B as an obesity gene in dogs and humans. Science. 2025 Mar 6:eads2145. doi: 10.1126/science.ads2145.

Chang JB, Apostolov AM, Soliai MM, Hecker J,Barnhill CP, Stapleton Smith LM, Mathew AS, Nierenberg JL,Diao J, Fernando CD, Chen Q, Dulken BW,Petukhov A, Lange C, Altman R, Josephs TM, Lasky-Su JA, Gorvin CM, Roberts MS, Adler SH, Fox JC, Ji S. An allelic series of the calcium sensing receptor and underdiagnosis of genetically driven hypocalcemia. Am J Hum Genet. 2025. 112(8):1818-1832. doi: 10.1016/j.ajhg.2025.06.013.

Jamaluddin A, Wyatt RA, Lee J, Dowsett GKC, Tadross JA, Broichhagen J, Yeo GSH, Levitz J, Gorvin CM. The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling. Science Signal. 2025. 18(917):eadu4315. doi: 10.1126/scisignal.adu4315.

Wyatt RA, Jamaluddin A, Mistry V, Quinn C, Gorvin CM. Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways. Hum Mol Genet. 2025 Jan 14:ddaf005. doi: 10.1093/hmg/ddaf005.

Benson MR, Wyatt RA, Levine MA, Gorvin CM. An activating calcium-sensing receptor variant with biased signaling reveals a critical residue for Gα11 coupling. J Bone Miner Res. 2025 Feb 2;40(2):270-282. doi: 10.1093/jbmr/zjae199.

Wyatt RA, Gallagher MT, Zha L, McCabe CJ, Gorvin CM. Identification of a calcium-sensing receptor motif able to direct spatially distinct endosomal signaling pathways. iScience. 2025. 28(6):112651.

Hansen MS, Søe K, Christensen LL, Fernandez-Guerra P, Hansen NW, Wyatt RA, Martin C, Hardy RS, Andersen TL, Olesen JB, Hartmann B, Rosenkilde MM, Kassem M, Rauch A, Gorvin CM, Frost M. GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells. Eur J Endocrinol 188, (2023).

Dershem R, Gorvin CM, Metpally RPR, Krishnamurthy S, Smelser DT, Hannan FM, Carey DJ, Thakker RV, Breitwieser GE; Regeneron Genetics Center. Regeneron Genetics, Familial Hypocalciuric Hypercalcemia Type 1 and Autosomal-Dominant Hypocalcemia Type 1: Prevalence in a Large Healthcare Population. Am J Hum Genet 106, 734-747 (2020).

Gorvin CM, Rogers A, Hastoy B, Tarasov AI, Frost M, Sposini S, Inoue A, Whyte MP, Rorsman P, Hanyaloglu AC, Breitwieser GE, Thakker RV. AP2sigma Mutations Impair Calcium-Sensing Receptor Trafficking and Signaling, and Show an Endosomal Pathway to Spatially Direct G-Protein Selectivity. Cell Rep 22, 1054-1066 (2018).

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