Dr Caroline Gorvin

Institute of Metabolism and Systems Research
Senior Research Fellow

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. She is currently establishing her research group investigating metabolic GPCRs and how they integrate hormonal signals to regulate appetite.

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. Caroline moved to the IMSR in January 2018 to establish her research group investigating metabolic GPCRs.

Research

Caroline’s research group investigates how impairments in the trafficking and signalling of membrane proteins contribute to endocrine disorders. This has previously focussed on how genetic alterations in the class C GPCR, calcium-sensing receptor, and components of its signalling pathway, contribute to human disorders of calcium homeostasis.

The Gorvin group currently has active research programmes investigating:

1) How metabolic GPCRs cross-talk and interact to regulate appetite (funded by an Academy of Medical Sciences Springboard Award), and

2) The interaction between GPCRs in bone metabolism and obesity (funded by Novo Nordisk).

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

Current group members:

Dominic Alcock (research technician)

Morten Steen Hansen (visiting clinical PhD student from University of Southern Denmark)

Other activities

Basic science lead for the Society for Endocrinology Bone and Calcium Network

Publications

Recent publications

Article

Gorvin, CM 2019, 'Molecular and clinical insights from studies of calcium-sensing receptor mutations', Journal of Molecular Endocrinology, vol. 63, no. 2, pp. R1-R16. https://doi.org/10.1530/JME-19-0104

Gorvin, CM, Loh, N, Stechman, M, Falcone, S, Hannan, FM, Ahmad, B, Piret, S, Reed, A, Jeyabalan, J, Leo, P, Marshall, M, Sethi, S, Bass, P, Roberts, I, Sanderson, J, Wells, S, Hough, T, Bentley, L, Christie, P, Simon, M, Mallon, A-M, Schulz, H, Cox, R, Brown, M, Huebner, N, Brown, S & Thakker, RV 2019, 'Mice with a Brd4 mutation represent a new model of nephrocalcinosis', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3695

Gorvin, CM, Newey, PJ, Rogers, A, Stokes, V, Neville, MJ, Lines, KE, Ntali, G, Lees, P, Morrison, PJ, Singhellakis, PN, Malandrinou, FC, Karavitaki, N, Grossman, AB, Karpe, F & Thakker, RV 2018, 'Association of prolactin receptor (PRLR) variants with prolactinomas', Human Molecular Genetics. https://doi.org/10.1093/hmg/ddy396

Gorvin, CM, Ahmad, B, Stechman, M, Loh, N, Hough, T, Leo, P, Marshall, M, Sethi, S, Bentley, L, Piret, S, Reed, A, Jeyabalan, J, Christie, P, Wells, S, Simon, M, Mallon, A-M, Schulz, H, Huebner, N, Brown, M, Cox, R, Brown, S & Thakker, R 2018, 'An N-ethyl-N-nitrosourea (ENU)-induced Tyr265Stop mutation of the DNA polymerase accessory subunit gamma 2 (Polg2) is associated with renal calcification in mice', Journal of Bone and Mineral Research. https://doi.org/10.1002/jbmr.3624

Gorvin, CM, Frost, M, Malinauskas, T, Cranston, T, Boon, H, Siebold, C, Jones, EY, Hannan, FM & Thakker, RV 2018, 'Calcium-sensing receptor residues with loss- and gain-of-function mutations are located in regions of conformational change and cause signalling bias', Human Molecular Genetics. https://doi.org/10.1093/hmg/ddy263

Patel, J, Chuaiphichai, S, Douglas, G, Gorvin, CM & Channon, KM 2018, 'Vascular wall regulator of G-protein signaling-1 (RGS-1) is required for angiotensin II-mediated blood pressure control', Vascular Pharmacology. https://doi.org/10.1016/j.vph.2018.04.002

Gorvin, CM, Babinsky, VN, Malinauskas, T, Nissen, PH, Schou, AJ, Hanyaloglu, AC, Siebold, C, Jones, EY, Hannan, FM & Thakker, RV 2018, 'A calcium-sensing receptor mutation causing hypocalcemia disrupts a transmembrane salt bridge to activate β-arrestin-biased signaling.', Science signaling, vol. 11, no. 518, eaan3714. https://doi.org/10.1126/scisignal.aan3714

Gorvin, CM, Rogers, A, Hastoy, B, Tarasov, AI, Frost, M, Sposini, S, Inoue, A, Whyte, MP, Rorsman, P, Hanyaloglu, AC, Breitwieser, GE & Thakker, RV 2018, 'AP2σ mutations impair calcium-sensing receptor trafficking and signaling revealing an endosomal pathway that spatially directs G-protein selectivity', Cell Reports, vol. 22, no. 4, pp. 1054-1066. https://doi.org/10.1016/j.celrep.2017.12.089

Gorvin, CM, Hannan, FM, Cranston, T, Valta, H, Makitie, O, Schalin-Jantti, C & Thakker, RV 2018, 'Cinacalcet rectifies hypercalcemia in a patient with familial hypocalciuric hypercalcemia Type 2 (FHH2) caused by a germline loss-of-function Gα11 mutation', Journal of Bone and Mineral Research, vol. 33, no. 1, pp. 32-41. https://doi.org/10.1002/jbmr.3241

Gorvin, CM, Metpally, R, Stokes, VJ, Hannan, FM, Krishnamurthy, SB, Overton, JD, Reid, JG, Breitwieser, GE & Thakker, RV 2018, 'Large-scale exome datasets reveal a new class of adaptor-related protein complex 2 sigma subunit (AP2σ) mutations, located at the interface with the AP2 alpha subunit, that impair calcium-sensing receptor signalling', Human Molecular Genetics. https://doi.org/10.1093/hmg/ddy010

Howles, SA, Hannan, FM, Gorvin, CM, Piret, SE, Paudyal, A, Stewart, M, Hough, TA, Nesbit, MA, Wells, S, Brown, SD, Cox, RD & Thakker, RV 2017, 'Cinacalcet corrects hypercalcemia in mice with an inactivating Gα11 mutation', JCI Insight, vol. 2, no. 20. https://doi.org/10.1172/jci.insight.96540

Gorvin, CM, Rogers, A, Stewart, M, Paudyal, A, Hough, TA, Teboul, L, Wells, S, Brown, S, Cox, RD & Thakker, RV 2017, 'N-ethyl-N-nitrosourea induced adaptor protein 2 sigma subunit 1 (Ap2s1) mutations establish Ap2s1 loss-of-function mice', Journal of Bone and Mineral Research, vol. 1, no. 1, pp. 3-15. https://doi.org/10.1002/jbm4.10001

Babinsky, VN, Hannan, FM, Ramracheya, RD, Zhang, Q, Nesbit, MA, Hugill, A, Bentley, L, Hough, TA, Joynson, E, Stewart, M, Aggarwal, A, Prinz-Wohlgenannt, M, Gorvin, CM, Kallay, E, Wells, S, Cox, RD, Richards, D, Rorsman, P & Thakker, RV 2017, 'Mutant mice with calcium-sensing receptor activation have hyperglycemia that is rectified by calcilytic therapy', Endocrinology, vol. 158, no. 8, pp. 2486-2502. https://doi.org/10.1210/en.2017-00111

Gorvin, CM, Hannan, FM, Howles, SA, Babinsky, VN, Piret, SE, Rogers, A, Freidin, AJ, Stewart, M, Paudyal, A, Hough, TA, Nesbit, MA, Wells, S, Vincent, TL, Brown, SDM, Cox, RD & Thakker, RV 2017, 'Gα11 mutation in mice causes hypocalcemia rectifiable by calcilytic therapy', JCI Insight, vol. 2, no. 3, pp. e91103. https://doi.org/10.1172/jci.insight.91103