Dr Caroline Gorvin

Institute of Metabolism and Systems Research
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: Institute of Metabolism and Systems Research
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 in 2007 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 the IMSR in January 2018 to establish her research group. Caroline’s research group has active research programmes investigating:

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

2) The role of metabolic GPCRs in bone metabolism (funded by Novo Nordisk),

3) 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 is a visiting researcher at 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 three 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.

GPCRs involved in bone metabolism

In collaboration with researchers at the University of Southern Denmark, Dr Gorvin’s research focusses on understanding how GPCRs contribute to bone metabolism. Current research areas include: the effect of the hormones GIP and GLP-1 on human bone cell activity and defining the roles of orphan GPCRs in osteoclast activity.

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)
Maria Price (PhD Metabolism and Systems Research)
Morten Steen Hansen (visiting clinical PhD student from University of Southern Denmark)

Other activities

Member of the MRC IAA Management Group
Member of the Programme Organising Committee for the Society for Endocrinology.
Member of the Science Committee 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 Institute of Metabolism & Systems Research (IMSR) and the Centre of Membrane Proteins & Receptors (COMPARE)

Publications

W. Xu, M. M. F. Qadir, D. Nasteska, P. Mota de Sa, C. M. Gorvin, M. Blandino-Rosano, C. R. Evans, T. Ho, E. Potapenko, R. Veluthakal, F. B. Ashford, S. Bitsi, J. Fan, M. Bhondeley, K. Song, V. N. Sure, S. Sakamuri, L. Schiffer, W. Beatty, R. Wyatt, D. E. Frigo, X. Liu, P. V. Katakam, W. Arlt, J. Buck, L. R. Levin, T. Hu, J. Kolls, C. F. Burant, A. Tomas, M. J. Merrins, D. C. Thurmond, E. Bernal-Mizrachi, D. J. Hodson, F. Mauvais-Jarvis. Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic beta cells. Cell Rep 42, 112529 (2023).

M. S. Hansen, K. Soe, L. L. Christensen, P. Fernandez-Guerra, N. W. Hansen, R. A. Wyatt, C. Martin, R. S. Hardy, T. L. Andersen, J. B. Olesen, B. Hartmann, M. M. Rosenkilde, M. Kassem, A. Rauch, C. M. Gorvin^$, M. Frost, GIP reduces osteoclast activity and improves osteoblast survival in primary human bone cells. Eur J Endocrinol 188, (2023).

H. A. Abid, A. Inoue, C. M. Gorvin. Heterogeneity of G protein activation by the calcium-sensing receptor. J Mol Endocrinol 67, 41-53 (2021).

R. Dershem, C. M. Gorvin, R. P. R. Metpally, S. Krishnamurthy, D. T. Smelser, F. M. Hannan, D. J. Carey, R. V. Thakker, G. E. Breitwieser, C. 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).

C. M. Gorvin, A. Rogers, B. Hastoy, A. I. Tarasov, M. Frost, S. Sposini, A. Inoue, M. P. Whyte, P. Rorsman, A. C. Hanyaloglu, G. E. Breitwieser, R. V. Thakker, 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).

C. M. Gorvin, V. N. Babinsky, T. Malinauskas, P. H. Nissen, A. J. Schou, A. C. Hanyaloglu, C. Siebold, E. Y. Jones, F. M. Hannan, R. V. Thakker, A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate beta-arrestin-biased signaling. Sci Signal 11, (2018).

C. M. Gorvin, F. M. Hannan, S. A. Howles, V. N. Babinsky, S. E. Piret, A. Rogers, A. J. Freidin, M. Stewart, A. Paudyal, T. A. Hough, M. A. Nesbit, S. Wells, T. L. Vincent, S. D. Brown, R. D. Cox, R. V. Thakker. Galpha(11) mutation in mice causes hypocalcemia rectifiable by calcilytic therapy. JCI Insight 2, e91103 (2017).

S. A. Howles, F. M. Hannan, V. N. Babinsky, A. Rogers, C. M. Gorvin, N. Rust, T. Richardson, M. J. McKenna, M. A. Nesbit, R. V. Thakker, Cinacalcet for Symptomatic Hypercalcemia Caused by AP2S1 Mutations. N Engl J Med 374, 1396-1398 (2016).

P. J. Newey, C. M. Gorvin*, S. J. Cleland, C. B. Willberg, M. Bridge, M. Azharuddin, R. S. Drummond, P. A. van der Merwe, P. Klenerman, C. Bountra, R. V. Thakker, Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med 369, 2012-2020 (2013).

C. M. Gorvin, M. J. Wilmer, S. E. Piret, B. Harding, L. P. van den Heuvel, O. Wrong, P. S. Jat, J. D. Lippiat, E. N. Levtchenko, R. V. Thakker, Receptor-mediated endocytosis and endosomal acidification is impaired in proximal tubule epithelial cells of Dent disease patients. Proc Natl Acad Sci U S A 110, 7014-7019 (2013

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