Our Work
Re-coding of G protein-coupled receptor signaling enables emergent cellular behavior. Dehkhoda F, Ringuet M.T., Whitfield E.A., Mutunduwe K, Nowell C.J., Misganaw D, Xu Z, Hossain A.M., Fothergill L.J., McDougall S.J., Furness J.B., Furness S.G.B. bioRxiv 2023.12.18.572241; doi: https://doi.org/10.1101/2023.12.18.572241
2023
Ringuet MT, Koo A, Furness SGB, McDougall SJ, Furness JB. Sites and mechanisms of action of colokinetics at dopamine, ghrelin and serotonin receptors in the rodent lumbosacral defecation centre. J Physiol. 2023 Dec;601(23):5195-5211. doi: 10.1113/JP285217. Epub 2023 Sep 29. PMID: 37772438.
2024
2022
Targeting appetite and satiety in diabetes and obesity, via G protein-coupled receptors. Piper NBC, Whitfield EA, Stewart GD, Xu X, Furness SGB. Biochem Pharmacol. 2022 Jun 6;202:115115. doi: 10.1016/j.bcp.2022.115115. Epub ahead of print. PMID: 35671790.
Bloxham CJ, Hulme KD, Fierro F, Fercher C, Pegg CL, O'Brien SL, Foster SR, Short KR, Furness SGB, Reichelt ME, Niv MY, Thomas WG. Cardiac human bitter taste receptors contain naturally occurring variants that alter function. Biochem Pharmacol. 2024 Jan;219:115932. doi: 10.1016/j.bcp.2023.115932. Epub 2023 Nov 19. PMID: 37989413.
2021
Discovery of a Positive Allosteric Modulator of Cholecystokinin Action at CCK1R in Normal and Elevated Cholesterol. Harikumar KG, Coudrat T, Desai AJ, Dong M, Dengler DG, Furness SGB, Christopoulos A, Wootten D, Sergienko EA, Sexton PM, Miller LJ. Front Endocrinol (Lausanne). 2021 Dec 7;12:789957. doi: 10.3389/fendo.2021.789957. PMID: 34950108; PMCID: PMC8689142.
G protein‐coupled receptor interactions and modification of signalling involving the ghrelin receptor, GHSR1a. Ringuet MT, Furness JB and Furness SGB (2021). Journal of Neuroendocrinology, e13077. doi: 10.1111/jne.13077
Methods to measure calcitonin receptor activity, up-regulated in cell stress, apoptosis and autophagy. Wookey PJ, Gupta P, Bittencourt L, Cheung S, Hare D, and Furness SGB (2021). F1000Research, 10 1019, 1019. doi: 10.12688/f1000research.72845.1
Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. Mobbs JI, Belousoff MJ, Harikumar KG, Piper SJ, Xu X, Furness SGB, Venugopal H, Christopoulos A, Danev R, Wootten D, Thal DM, Miller LJ, Sexton PM. PLoS Biol. 2021 Jun 4;19(6):e3001295. doi: 10.1371/journal.pbio.3001295. eCollection 2021 Jun.
AM833 is a novel agonist of calcitonin family G protein-coupled receptors: pharmacological comparison to six selective and non-selective agonists. Fletcher MM, Keov P, Truong TT, Mennen G, Hick CA, Zhao P, Furness SGB, Kruse T, Clausen TR, Wootten D, Sexton PM. J. Pharmacol. Exp. Ther. 2021 Mar 16. DOI: https://doi.org/10.1124/jpet.121.000567
Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Šenel P, Stewart GD, Liang Y-L, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D. Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists. Molecular Cell. 2020 http://doi.org/10.1016/j.molcel.2020.09.020
2020
Gupta P, Furness SGB, Bittencourt L, Hare DL, Wookey PJ. Building the case for the calcitonin receptor as a viable target for the treatment of glioblastoma. Ther Adv Med Oncol. 2020 Dec 18;12:1758835920978110. doi: 10.1177/1758835920978110.
Furness JB, Pustovit RV, Syder AJ, Ringuet MT, Yoo EJ, Fanjul A, Wykosky J, Fothergill LJ, Whitfield EA, Furness SGB. Dopamine and ghrelin receptor co-expression and interaction in the spinal defecation centers. Neurogastroenterol Motil. 2020 Dec 2;:e14051. https://doi.org/10.1111/nmo.14051
Liu M*, Whitfield EA*, Fothergill LJ, Furness JB, Wade JD, Furness SGB#, Houssain MA#. Design, synthesis and characterization of a fluorescently labeled functional analog of full-length human ghrelin. Biochem Biophys Res Commun. 2020 Sep. 24 https://doi.org/10.1016/j.bbrc.2020.09.028
Dong M, Deganutti G, Piper SJ, Liang YL, Khoshouei M, Belousoff MJ, Harikumar KG, Reynolds CA, Glukhova A, Furness SGB, Christopoulos A, Danev R, Wootten D, Sexton PM, Miller LJ. Structure and dynamics of the active Gs-coupled human secretin receptor. Nat Commun. 2020 Aug 18;11(1):4137. doi: 10.1038/s41467-020-17791-4. PMID: 32811827
Liang YL, Belousoff MJ, Fletcher MM, Zhang X, Khoshouei M, Deganutti G, Koole C, Furness SGB, Miller LJ, Hay DL, Christopoulos A, Reynolds CA, Danev R, Wootten D, Sexton PM. Structure and Dynamics of Adrenomedullin Receptors AM1 and AM2 Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins. ACS Pharmacol Transl Sci. 2020 Mar 20;3(2):263-284. doi: 10.1021/acsptsci.9b00080. PMID: 32296767; PMCID: PMC7155201.
Zhao P, Liang YL, Belousoff MJ, Deganutti G, Fletcher MM, Willard FS, Bell MG, Christe ME, Sloop KW, Inoue A, Truong TT, Clydesdale L, Furness SGB, Christopoulos A, Wang MW, Miller LJ, Reynolds CA, Danev R, Sexton PM, Wootten D. Activation of the GLP-1 receptor by a non-peptidic agonist. Nature. 2020 Jan;577(7790):432-436. doi:10.1038/s41586-019-1902-z. Epub 2020 Jan 8. PubMed PMID: 31915381.
2019
Nguyen HTH, Wood RJ, Prawdiuk AR, Furness SGB, Xiao J, Murray SS, Fletcher JL. TrkB Agonist LM22A-4 Increases Oligodendroglial Populations During Myelin Repair in the Corpus Callosum. Front Mol Neurosci. 2019 Aug 27;12:205. doi:10.3389/fnmol.2019.00205. eCollection 2019. PubMed PMID: 31507374; PubMed Central PMCID: PMC6718610.
Pham V, Zhu Y, DalMaso E, Reynolds CA, Deganutti G, Atanasio S, Hick CA, Yang D, Christopoulos A, Hay DL, Furness SGB, Wang M-W, Wootten D, Sexton PM. Deconvoluting the Molecular Control of Binding and Signaling at the Amylin 3 Receptor: RAMP3 Alters Signal Propagation through Extracellular Loops of the Calcitonin Receptor. ACS Pharmacology & Translational Science. American Chemical Society; 2019 Mar 18;:1–15. https://doi.org/10.1021/acsptsci.9b00010
Ostrovskaya A, Hick C, Hutchinson DS, Stringer BW, Wookey PJ, Wootten D, Sexton PM, Furness SGB. Expression and activity of the calcitonin receptor family in a sample of primary human high-grade gliomas. BMC Cancer. 2019 Feb 18;19(1):157. doi: 10.1186/s12885-019-5369-y.
Dal Maso E, Glukhova A, Zhu Y, Garcia-Nafria J, Tate CG, Atanasio S,Reynolds CA, Ramírez-Aportela E, Carazo J-M, Hick CA, Furness SGB, Hay DL, Liang Y-L, Miller LJ, Christopoulos A, Wang M-W, Wootten D, and Sexton PM. The Molecular Control of Calcitonin Receptor Signaling. ACS Pharmacology & Translational Science. 2019;:acsptsci.8b00056. https://doi.org/10.1021/acsptsci.8b00056
Zhao P, Furness SGB. The nature of efficacy at G protein-coupled receptors. Biochem Pharmacol. 2019 Dec;170:113647. doi: 10.1016/j.bcp.2019.113647. Epub 2019 Oct 1. Review. PubMed PMID: 31585071.
Draper-Joyce C, Furness SGB. Conformational Transitions and the Activation of Heterotrimeric G Proteins by G Protein-Coupled Receptors. ACS Pharmacology & Translational Science. American Chemical Society; 2019 Jul 19;:1–6. https://doi.org/10.1021/acsptsci.9b00054
Furness SGB, Christopoulos A, Sexton PM, Wootten D. Differential engagement of polar networks in the glucagon-like peptide 1 receptor by endogenous variants of the glucagon-like peptide 1. Biochem Pharmacol. 2018 Aug 25;156:223-240. doi: 10.1016/j.bcp.2018.08.033.
2018
Liang Y-L, Zhao P, Draper-Joyce CJ, Baltos J-A, Glukhova A, Truong TT, May LT, Christopoulos A, Wootten D, Sexton PM, and Furness SGB. Dominant Negative G Proteins Enhance Formation and Purification of Agonist-GPCR-G Protein Complexes for Structure Determination. ACS Pharmacology & Translational Science. 2018 1(1), 12-20 https://doi.org/10.1021/acsptsci.8b00017
Draper-Joyce CJ, Khoshouei M, Thal DM, Liang YL, Nguyen ATN, Furness SGB, Venugopal H, Baltos JA, Plitzko JM, Danev R, Baumeister W, May LT, Wootten D, Sexton PM, Glukhova A, Christopoulos A. Structure of the adenosine-bound human adenosine A(1) receptor-G(i) complex. Nature. 2018 Jun;558(7711):559-563. doi: 10.1038/s41586-018-0236-6. PubMed PMID: 29925945.
Liang YL, Khoshouei M, Glukhova A, Furness SGB, Zhao P, Clydesdale L, Koole C, Truong TT, Thal DM, Lei S, Radjainia M, Danev R, Baumeister W, Wang MW, Miller LJ, Christopoulos A, Sexton PM, Wootten D. Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature. 2018 Mar 1;555(7694):121-125. doi: 10.1038/nature25773. PubMed PMID: 29466332.
Dal Maso E, Zhu Y, Pham V, Reynolds CA, Deganutti G, Hick CA, Yang D, Christopoulos A, Hay DL, Wang MW, Sexton PM, Furness SGB*, Wootten D*. Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy. Biochem Pharmacol. 2018 Apr;150:214-244. doi: 10.1016/j.bcp.2018.02.005. PubMed PMID: 29454620; PubMed Central PMCID: PMC5908784.
Dal Maso E, Just R, Hick C, Christopoulos A, Sexton PM, Wootten D, Furness SGB. Characterization of signalling and regulation of common calcitonin receptor splice variants and polymorphisms. Biochem Pharmacol. 2018 Feb;148:111-129. https://doi.org/10.1016/j.bcp.2017.12.016. PubMed PMID: 29277692.
Gilabert-Oriol R*, Furness SGB*, Stringer BW, Weng A, Fuchs H, Day BW, Kourakis A, Boyd AW, Hare DL, Thakur M, Johns TG, Wookey PJ (2017). Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma. Cancer Immunol Immunother. 2017 Sep;66(9):1217-1228. doi: 10.1007/s00262-017-2013-z. PubMed PMID: 28501939.
2017
Liang YL, Khoshouei M, Radjainia M, Zhang Y, Glukhova A, Tarrasch J, Thal DM, Furness SGB, Christopoulos G, Coudrat T, Danev R, Baumeister W, Miller LJ, Christopoulos A, Kobilka BK, Wootten D, Skiniotis G, Sexton PM. Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. Nature. 2017 Jun 1;546(7656):118-123. doi: 10.1038/nature22327. PubMed PMID: 28437792.
Furness SG, Sexton PM (2017). Coding GPCR-G protein specificity. Cell Res. 2017 Oct;27(10):1193-1194. doi: 10.1038/cr.2017.92. PubMed PMID: 28695889.
Furness SG, Wootten D, Sexton PM. What determines the magnitude of cellular response for activation of G protein-coupled receptors? Cell Cycle. 2017 Mar 4;16(5):392-394. doi: 10.1080/15384101.2016.1271634. PubMed PMID: 28055294.
Furness SG, Liang YL, Nowell CJ, Halls ML, Wookey PJ, Dal Maso E, Inoue A, Christopoulos A, Wootten D, Sexton PM. Ligand-Dependent Modulation of G Protein Conformation Alters Drug Efficacy. Cell. 2016 Oct 20;167(3):739-749.e11. doi: 10.1016/j.cell.2016.09.021. PubMed PMID: 27720449.
2016
Furness SG, Hare DL, Kourakis A, Turnley AM, Wookey PJ. A novel ligand of calcitonin receptor reveals a potential new sensor that modulates programmed cell death. Cell Death Discov. 2016 Oct 10;2:16062. https://doi.org/10.1038/cddiscovery.2016.62 PubMed PMID: 27777788; PubMed Central PMCID: PMC5056446.
Wootten D, Reynolds CA, Smith KJ, Mobarec JC, Furness SG, Miller LJ, Christopoulos A, Sexton PM (2016). Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor. Biochem Pharmacol. Oct 15;118:68-87. doi: 10.1016/j.bcp.2016.08.015. Epub 2016 Aug 26. PubMed PMID: 27569426; PubMed Central PMCID: PMC5063953.
Wootten D, Reynolds CA, Smith KJ, Mobarec JC, Koole C, Savage EE, Pabreja K, Simms J, Sridhar R, Furness SG, Liu M, Thompson PE, Miller LJ, Christopoulos A, Sexton PM. The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism. Cell. 2016 Jun 16;165(7):1632-43. doi:10.1016/j.cell.2016.05.023. PubMed PMID: 27315480; PubMed Central PMCID: PMC4912689.
Wootten D, Reynolds CA, Koole C, Smith KJ, Mobarec JC, Simms J, Quon T, Coudrat T, Furness SG, Miller LJ, Christopoulos A, Sexton PM (2016). A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures. Mol Pharmacol. Mar;89(3):335-47. doi: 10.1124/mol.115.101246. Epub 2015 Dec 23. PubMed PMID: 26700562; PubMed Central PMCID: PMC4767408.
Cook AE, Mistry SN, Gregory KJ, Furness SG, Sexton PM, Scammells PJ, Conigrave AD, Christopoulos A, Leach K. Biased allosteric modulation at the CaS receptor engendered by structurally diverse calcimimetics. Br J Pharmacol. 2015 Jan;172(1):185-200. doi: 10.1111/bph.12937. PubMed PMID: 25220431; PubMed Central PMCID: PMC4280977.
2015
Andreassen KV, Hjuler ST, Furness SG, Sexton PM, Christopoulos A, Nosjean O, Karsdal MA, Henriksen K. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias. PLoS ONE. 2014 Mar 18;9(3):e92042. doi: 10.1371/journal.pone.0092042
2014
Pabreja K, Mohd MA, Koole C, Wootten D, Furness SG. Molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by GLP-1R activation. Br J Pharmacol. 2014 Mar;171(5):1114-28. doi: 10.1111/bph.12313. PubMed PMID: 23889512.
Savage EE, Wootten D, Christopoulos A, Sexton PM, Furness SG. A simple method to generate stable cell lines for the analysis of transient protein-protein interactions. Biotechniques. 2013 Apr;54(4):217-21. doi: 10.2144/000114013. PubMed PMID: 23581469.
2013
Koole C, Pabreja K, Savage EE, Wootten D, Furness SG, Miller LJ, Christopoulos A, Sexton PM. Recent advances in understanding GLP-1R (glucagon-like peptide-1 receptor) function. Biochem Soc Trans. 2013 Feb 1;41(1):172-9. doi: 10.1042/BST20120236. Review. PubMed PMID: 23356279.
Harikumar KG, Wootten D, Pinon DI, Koole C, Ball AM, Furness SG, Graham B, Dong M, Christopoulos A, Miller LJ, Sexton PM. Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery. Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18607-12. doi: 10.1073/pnas.1205227109. PubMed PMID: 23091034; PubMed Central PMCID: PMC3494884.
2012
Hao N, Lee KL, Furness SG, Bosdotter C, Poellinger L, Whitelaw ML (2012). Xenobiotics and loss of cell adhesion drive distinct transcriptional outcomes by aryl hydrocarbon receptor signaling. Mol Pharmacol. 2012 Dec;82(6):1082-93. doi: 10.1124/mol.112.078873. Aug 30. PubMed PMID: 22936816.
Willard FS, Wootten D, Showalter AD, Savage EE, Ficorilli J, Farb TB, Bokvist K, Alsina-Fernandez J, Furness SG, Christopoulos A, Sexton PM, Sloop KW. Small molecule allosteric modulation of the glucagon-like peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin. Mol Pharmacol. 2012 Dec;82(6):1066-73. doi: 10.1124/mol.112.080432. PubMed PMID: 22930710.
Sato M, Hutchinson DS, Halls ML, Furness SG, Bengtsson T, Evans BA, Summers RJ (2012). Interaction with caveolin-1 modulates G protein coupling of mouse β3-adrenoceptor. J Biol Chem. Jun 8;287(24):20674-88. doi: 10.1074/jbc.M111.280651. Epub 2012 Apr 25. PubMed PMID: 22535965; PubMed Central PMCID: PMC3370250.
Wookey PJ, McLean CA, Hwang P, Furness SG, Nguyen S, Kourakis A, Hare DL, Rosenfeld JV. The expression of calcitonin receptor detected in malignant cells of the brain tumour glioblastoma multiforme and functional properties in the cell line A172. Histopathology. 2012 May;60(6):895-910. doi: 10.1111/j.1365-2559.2011.04146.x. PubMed PMID: 22335784.
Furness SG, Wootten D, Christopoulos A, Sexton PM. Consequences of splice variation on Secretin family G protein-coupled receptor function. Br J Pharmacol. 2012 May;166(1):98-109. doi: 10.1111/j.1476-5381.2011.01571.x. Review. PubMed PMID: 21718310; PubMed Central PMCID: PMC3415641.
prior to 2012
Whelan F, Hao N, Furness SG, Whitelaw ML, Chapman-Smith A. (2010). Amino acid substitutions in the aryl hydrocarbon receptor ligand binding domain reveal YH439 as an atypical AhR activator. Mol Pharmacol. 77(6):1037-46. DOI: 10.1124/mol.109.062927 Epub 2010 Mar 15. PubMed PMID: 20231332.
Furness SG, Whelan F. (2009) The pleiotropy of dioxin toxicity--xenobiotic misappropriation of the aryl hydrocarbon receptor's alternative physiological roles. Pharmacol Ther. 124(3):336-53. DOI: 10.1016/j.pharmthera.2009.09.004 Epub 2009 Sep 23. PubMed PMID: 19781569.
Dave KA, Whelan F, Bindloss C, Furness SG, Chapman-Smith A, Whitelaw ML, Gorman JJ. Sulfonation and phosphorylation of regions of the dioxin receptor susceptible to methionine modifications. Mol Cell Proteomics. 2009 Apr;8(4):706-19. doi: 10.1074/mcp.M800459-MCP200. Epub 2008 Dec 4. PMID: 19059900
Furness SG & Whelan F. The pleiotropy of dioxin toxicity—xenobiotic misappropriation of the aryl hydrocarbon receptor's alternative physiological roles. Pharmacol Ther. 2009 Dec;124(3):336-53. doi: 10.1016/j.pharmthera.2009.09.004. PubMed PMID: 19781569.
Morfis M, Tilakaratne N, Furness S.G., Christopoulos G, Werry T.D., Christopoulos A, Sexton P.M. (2008) Receptor activity modifying proteins differentially modulate the G protein-coupling EFFICIENCY of amylin receptors. Endocrinology. 2008 Jul 3. [Epub ahead of print doi:10.1210/en.2007-1735]
Furness SGB & McNagny K. (2006) Beyond mere markers – functions for CD34 family sialomucins in hematopoiesis. Immunologic Research. 34:13-34 doi: 10.1385/IR:34:1:13
Tan PC, Furness SG, Merkens H, Lin S, McCoy ML, Roskelley CD, Kast J, McNagny KM. (2006) NHERF-1 is an hematopoietic ligand for a subset of the CD34 family of stem cell surface proteins. Stem Cells. 24, 1150-61. doi: 10.1634/stemcells.2005-0426