Dr Gemma Brierley
Lecturer in Comparative Biomedical Sciences
Dr. Brierley is a lecturer and research group leader in the Department of Comparative Biomedical Sciences. Dr. Brierley's research group is interested in understanding mechanisms that result in insulin resistance and the development of novel therapies to treat insulin resistance.
Research in Dr. Brierley's laboratory is currently funded by a project grant awarded by Diabetes UK.
Dr. Brierley completed her PhD at the University of Adelaide, Australia (including a sabbatical at the Weatherall Institute of Molecular Medicine, University of Oxford) where she investigated the interplay between insulin and IGF receptors and how they signal outcomes relevant to cancer biology. She was a Postdoctoral Fellow at the Commonwealth Scientific Industrial Research Organisation (CSIRO) in South Australia, where she worked on a varied and commercially orientated body of work related to improving early detection and diagnosis of colorectal cancer. Dr. Brierley then moved to the UK to undertake a second postdoctoral role at the University of Cambridge, Institute of Metabolic Science – Metabolic Research Labs (where she maintains Affiliate Principal Investigator and Visiting Scientist status ). During which, she expanded her understanding of the insulin/IGF system from its role in cancer biology to its role in metabolism. In 2021, Gemma moved on from the IMS-MRL to undertake a lectureship at Anglia Ruskin University, where she established her independent research laboratory and amassed a large amount of teaching experience in cell biology and biochemistry. In June 2024, Gemma left ARU to take up her current post at the RVC.
Professional Activities:
Diabetes UK - Diabetes Research Steering Group (Living with Diabetes Long-term) committee member (2024 - present)
Fellow of the Diabetes UK Innovators in Diabetes Programme (2018 - 2021)
Professional Member Diabetes UK (2014 - present)
Alumni of the Emerging Research Leaders Development Programme, University of Cambridge (2018)
Funding & Awards:
2025: Awarded (Lead Supervisor) - RVC Internal PhD Studentship Award
2023: Awarded (PrincipaI Investigator) - Diabetes UK 5-year Project Grant
2022: Awarded (PrincipaI Investigator) - Anglia Ruskin University Research Development Support Grant
2020: Shortlisted - Diabetes Research & Wellness Foundation Prof. David Matthews Non-clinical Fellowship
2020: Awarded (Joint PrincipaI Investigator) - University of Cambridge, MRL-IMS Directors Collaborative Award
2020: Awarded (PrincipaI Investigator) - Cambridge Philosophical Society Grant
2015: Awarded (named post-doc) - Diabetes UK 4-year Project Grant
2015: Awarded (PrincipaI Investigator) - Diabetes Research & Wellness Foundation Pump-priming grant
2014: Shortlisted - Diabetes UK RD Lawrence Career Development Fellowship
Research in the Brierley Laboratory aims to understand the mechanisms that result in insulin resistance and the development of novel therapies to treat insulin resistance.
Insulin resistance is defined as the reduced ability of insulin to lower blood glucose. Many people live in a state of compensated insulin resistance, where increased insulin levels can control blood glucose. Diabetes occurs when insulin secretion by the pancreas can no longer control blood glucose and there is an accompanying failure of the adipose tissue. Due to this, insulin resistance is a complex state of reduced insulin action in some tissues, and excess insulin action in others.
Extreme insulin resistance can be caused by genetic defects in the insulin receptor, and the most severe cause death in childhood despite best current treatment. The Brierley Laboratory, in collaboration with Prof. Robert Semple (University of Edinburgh), is currently developing agonistic antibodies that bypass the effect of the genetic mutations and restore receptor function. If successful, such antibodies could be a potentially life-saving treatment for rare forms of extreme insulin resistance and may augment current treatment for more common types of diabetes.
An understudied aspect of the insulin/IGF axis that controls development, growth, longevity, and metabolism are the hybrid receptors that form between the insulin receptor and the type-1 IGF receptor. One focus of the Brierley Laboratory is defining the role of these hybrid receptors in context of how cells interpret the signals from insulin and IGF-1 and how these control growth and metabolism. Deciphering these mechanisms is important for the understanding of normal physiology and the pathology of insulin resistance, diabetes and comorbidities such as cardiovascular disease and cancer.
Tomlinson PR, Knox R, Perisic O, Su HC, Brierley GV, Williams RL, Semple RK. Paradoxical dominant negative activity of an immunodeficiency-associated activating PIK3R1 variant. eLife. 2024. 13:RP94420
Gage MC, Harrington D, Brierley GV, Freathy RM, Gabriel BM, McNeilly AD, Meek CL, Roberts LD. Challenges and solutions for diabetes early career researchers in the COVID- 19 recovery: Perspectives of the Diabetes UK Innovators in Diabetes. Diabetic Medicine. 2022 Mar; 39(3):e14698
Brierley GV, and Semple RK. Insulin at 100 years – is rebalancing its action key to fighting obesity-related disease? Disease Model Mechanisms. 2021 Nov1;14(11):dmm049340
Brierley GV, Webber H, Rasijeff E, Grocott S, Siddle K, Semple RK. Anti-Insulin receptor antibodies improve glycaemic control in a mouse model of human insulin receptoropathy. Diabetes. 2020 Nov;69(11):2481-2489
Hammerle CM, Sandovici I, Brierley GV, Smith NM, Zimmer WE, Zvetkova I, Prosser HM, Sekita Y, Lam BYH, Ma M, Cooper WN, Vidal-Puig A, Ozanne SE, Medina-Gómez G, Constância M. Mesenchymal Igf2 is a major paracrine regulator of pancreatic growth and function. PLoS Genet. 2020 Oct 15;16(10):e1009069
Brierley GV, Siddle K, Semple RK. Evaluation of anti-insulin receptor antibodies as potential therapies for human insulin receptoropathy using cell culture models. Diabetologia. 2018 Jul; 61(7):1662-1675 Awarded front cover image for the July issue
Innaurato S*, Brierley GV*, Grasso V, Massimi A, Gaudino R, Sileno S, Bernardini S, Semple RK, Barbetti F. Severe insulin resistance in disguise: A familial case of reactive hypoglycaemia associated with a novel heterozygous INSR mutation. Pediatric Diabetes. 2018 Jun; 19(4):670-67 *Joint first authour
Groenveld MP*, Brierley GV*, Rocha NM, Siddle K, Semple RK. Acute knockdown of the insulin receptor or its substrate IRS1 and 2 in 3T3-L1 adipocytes suppresses adiponectin production. 2016 Feb18; 6: 21105 *Joint first authour
Fung KY, Tabor B, Buckley MJ, Priebe IK, Purins L, Pompeia C, Brierley GV, Lockett T, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Nice E, Adams TE, Burgess A, Cosgrove LJ. Blood-based protein biomarker panel for the detection of colorectal cancer. PLoS One. 2015 Mar 20; 10(3): e0120425
Henderson ST, Brierley GV, Surinya KH, Priebe IK, Catcheside DE, Wallace JC, Forbes BE, Cosgrove LJ. Delineation of the IGF-II C-domain elements involved in binding and activation of the IR-A, IR-B and IGF-1R. Growth Hormone & IGF Research. 2015 Feb; 25(1):20-7
Fung KY, Purins L, Priebe IK, Pompeia C, Brierley GV, Tabor B, Lockett T, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Burgess A, Nice E, Cosgrove LJ. Analysis of 32 blood-based protein biomarkers for their potential to diagnose colorectal cancer. J Mol Biomarkers Diagnosis S6:003. DOI: 10.4172/2155-9929.s6-003
Caruso M, Fung KYC, Moore J, Brierley GV, Cosgrove LJ, Thomas M, Cheetham G, Brook E, Fraser LM, Tin T, Tran H, & Ruszkiewicz A. Claudin-1 expression is elevated in colorectal cancer precursor lesions harbouring the BRAF V600E mutation. Translational Oncology 2014 7(4), 456-463 doi: 10/1016/j.tranon.2014.05.009
Brierley GV, Fung KYC, Purins L, Priebe IK, Tabor B, Lockett T, Nice E, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Burgess A, & Cosgrove LJ. Circulating levels of the Wnt antagonist Dkk-3 as a diagnostic marker for colorectal cancer. J Mol Biomark Diagnosis. 2013 S8-008 doi:10.4172/2155-9929.S8-008
Brierley GV, Priebe IK, Purins L, Fung KYC, Tabor B, Lockett T, Nice E, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Burgess A, & Cosgrove LJ. Serum concentrations of brain-derived neurotrophic factor (BDNF) are decreased in colorectal cancer patients. Cancer Biomarkers 2013 Jan 1; 13(2):67-73
Fung KYC, Priebe IK, Purins L, Tabor B, Brierley GV, Lockett T, Nice E, Gibbs P, Tie J, McMurrick P, Moore J, Ruszkiewicz A, Burgess A, & Cosgrove LJ. Performance of serum Lipocalin 2 as a diagnostic marker for colorectal cancer. Cancer Biomark. 2013 Jan1;13(2):75-79
Fung KYC, Brierley GV, Henderson ST, Hoffman P, McColl SR, Lockett T, Head R & Cosgrove LJ. Butyrate-induced apoptosis in HCT116 colorectal cancer cells includes induction of a cell stress response. J Proteome Res. 2011 April1; 10(4):1860-9
Fung KYC, Cursaro C, Lewanowitsch T, Brierley GV, McColl ST, Lockett T, Head R, Hoffman P, & Cosgrove LJ. A combined free-flow electrophoresis and DIGE approach to identify proteins regulated by butyrate in HT29 cells. Proteomics. 2011 Mar; 11(5):964-71
Dransfield DT, Cohen EH, Chang Q, Sparrow LG, Bentley JD, Dolezal O, Xiao X, Peat TS, Newman J, Pilling PA, Phan T, Priebe I, Brierley GV, Kastrapeli N, Kopacz K, Martik D, Wassaf D, Rank D, Conley G, Huang Y, Adams TE, & Cosgrove LJ. A human monoclonal antibody against IGF-II blocks the growth of human hepatocellular carcinoma cell lines in vitro and in vivo. Mol Cancer Therapeutics. 2010 Jun;9(6):1809-19
Brierley GV, Macaulay SL, Forbes BE, Wallace JC, Cosgrove LJ, & Macaulay VM. Silencing of the insulin receptor isoform A favors formation of type 1 insulin-like growth factor receptor (IGF-1R) homodimers and enhances ligand-induced IGF-1R activation and viability of human colon cancer cells. Endocrinology. 2010 April; 151(4): 1418-27
Denley A, Carrol JM, Brierley GV, Cosgrove LJ, Wallace JC, Forbes BE, & Roberts CT Jr. Differential activation of insulin receptor substrates 1 and 2 by insulin-like growth factors- activated insulin receptors. Mol Cell Biol. 2007 May; 27(10):3569-77.
Denley A, Brierley GV, Carroll JM, Lindenberg A, Booker GW, Cosgrove LJ, Wallace JC, Forbes BE, & Roberts CT Jr. Differential activation of insulin receptor isoforms by insulin-like growth factors is determined by the C domain. Endocrinology. 2006 Feb; 147(2):1029-36
Dr. Gemma Brierley delivers lectures on central metabolism and the endocrine control of blood glucose on the BVetMed and Gateway programmes. She is also a tutor to BVetMed students.