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Department of Pharmacology and Toxicology staff profiles

Professor Debbie Hay

PositionProfessor
DepartmentDepartment of Pharmacology and Toxicology

Research

After 18 years at the University of Auckland, Debbie moved to the University of Otago in 2020. Research in the Hay laboratory focuses on G protein-coupled receptors (GPCRs). These proteins are the cellular targets of natural hormones and are some of the most important drug targets. Her research aims to contribute to the development of medicines to treat migraine, among other conditions. Debbie is passionate about raising the profile of migraine in New Zealand and improving the lives of patients who have this condition.

Work in the lab spans a range of areas with local and international collaborators in academia and industry, including: pharmacology, medicinal chemistry, peptide chemistry, structural biology, molecular biology, immunohistochemistry and culture of cell lines and primary cells. A particular focus of the lab is class B GPCRs and their interactions with accessory proteins known as “receptor activity-modifying proteins”.

Debbie is a well-cited researcher (Web of Science, Highly Cited), who was elected Fellow of the British Pharmacological Society in 2018 (FBPhS). Other honours include the Gavin and Ann Kellaway Medical Research Fellowship for senior medical researchers (2018), an RSNZ James Cook Research Fellowship (2017), the prestigious 2015 Tregear Award (Australian Peptide Association), the 2013 Novartis Prize (British Pharmacological Society) and the 2013 Custom Science NZSBMB award.

She is an Editorial Board member of the British Journal of Pharmacology since 2015 (Editor Performance Award 2016), and Corresponding Member of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), chairing its subcommittee on nomenclature of CGRP peptide family receptors. This committee provides influential educational resources for pharmacologists and non-pharmacologists, the pharmaceutical industry and academia.

Debbie is an active mentor of young researchers, is a British Pharmacological Society Women in Pharmacology mentor (2012-present), and has given many invited talks on mentoring, such as 'Mentors: what are they and how do I find one', 'Keep calm and write a paper', 'Keep calm and write a grant application', for early career researchers.

Publications

Tasma, Z., Wills, P., Hay, D. L., & Walker, C. S. (2020). Agonist bias and agonist-dependent antagonism at corticotrophin releasing factor receptors. Pharmacology Research & Perspectives, 8(3), e00595. doi: 10.1002/prp2.595

Chuang, C.-L., & Hay, D. L. (2020). Amylin. In S. Offermanns & W. Rosenthal (Eds.), Encyclopaedia of molecular pharmacology. Cham, Switzerland: Springer. doi: 10.1007/978-3-030-21573-6_10021-1

Noh, D., Bower, R. L., Hay, D. L., Zhyvoloup, A., & Raleigh, D. P. (2020). Analysis of amylin consensus sequences suggests that human amylin is not optimized to minimize amyloid formation and provides clues to factors that modulate amyloidogenicity. ACS Chemical Biology, 15(6), 1408-1416. doi: 10.1021/acschembio.9b01050

Gingell, J. J., Rees, T. A., Hendrikse, E. R., Siow, A., Rennison, D., Scotter, J., … Hay, D. L. (2020). Distinct patterns of internalization of different calcitonin gene-related peptide receptors. ACS Pharmacology & Translational Science, 3(2), 296-304. doi: 10.1021/acsptsci.9b00089

Hendrikse, E. R., Liew, L. P., Bower, R. L., Bonnet, M., Jamaluddin, M. A., Prodan, N., … Hay, D. L. (2020). Identification of small-molecule positive modulators of calcitonin-like receptor-based receptors. ACS Pharmacology & Translational Science, 3(2), 305-320. doi: 10.1021/acsptsci.9b00108

Chapter in Book - Research

Pioszak, A. A., & Hay, D. L. (2020). RAMPs as allosteric modulators of the calcitonin and calcitonin-like class B G protein-coupled receptors. In C. J. Langmead (Ed.), From structure to clinical development: Allosteric modulation of G protein-coupled receptors. (pp. 115-141). Cambridge, MA: Academic Press. doi: 10.1016/bs.apha.2020.01.001

Chuang, C.-L., & Hay, D. L. (2020). Amylin. In S. Offermanns & W. Rosenthal (Eds.), Encyclopaedia of molecular pharmacology. Cham, Switzerland: Springer. doi: 10.1007/978-3-030-21573-6_10021-1

Hay, D. L. (2019). CGRP receptor biology: Is there more than one receptor? In S. Brain & P. Geppetti (Eds.), Calcitonin gene-related peptide (CGRP) mechanisms: Focus on migraine. (pp. 13-22). Cham, Switzerland: Springer. doi: 10.1007/164_2018_131

Gingell, J. J., Walker, C. S., & Hay, D. L. (2017). Class B GPCR: Receptors and RAMPs. In K. Herrick-Davis, G. Milligan & G. Di Giovanni (Eds.), G-protein-coupled receptor dimers. (pp. 289-305). Cham, Switzerland: Humana Press. doi: 10.1007/978-3-319-60174-8_11

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Journal - Research Article

Tasma, Z., Wills, P., Hay, D. L., & Walker, C. S. (2020). Agonist bias and agonist-dependent antagonism at corticotrophin releasing factor receptors. Pharmacology Research & Perspectives, 8(3), e00595. doi: 10.1002/prp2.595

Lu, B. L., Loomes, K. M., Hay, D. L., Harris, P. W. R., & Brimble, M. A. (2020). Synthesis of isotopically labelled αCGRP8-37 and its lipidated analogue. Journal of Labelled Compounds & Radiopharmaceuticals, 63, 325-332. doi: 10.1002/jlcr.3838

Gingell, J. J., Rees, T. A., Hendrikse, E. R., Siow, A., Rennison, D., Scotter, J., … Hay, D. L. (2020). Distinct patterns of internalization of different calcitonin gene-related peptide receptors. ACS Pharmacology & Translational Science, 3(2), 296-304. doi: 10.1021/acsptsci.9b00089

Noh, D., Bower, R. L., Hay, D. L., Zhyvoloup, A., & Raleigh, D. P. (2020). Analysis of amylin consensus sequences suggests that human amylin is not optimized to minimize amyloid formation and provides clues to factors that modulate amyloidogenicity. ACS Chemical Biology, 15(6), 1408-1416. doi: 10.1021/acschembio.9b01050

Liang, Y.-L., Belousoff, M. J., Fletcher, M. M., Zhang, X., Khoshouei, M., Deganutti, G., … Hay, D. L., … Sexton, P. M. (2020). Structure and dynamics of adrenomedullin receptors AM1 and AM2 reveal key mechanisms in the control of receptor phenotype by receptor activity-modifying proteins. ACS Pharmacology & Translational Science, 3(2), 263-284. doi: 10.1021/acsptsci.9b00080

Garelja, M. L., Au, M., Brimble, M. A., Gingell, J. J., Hendrikse, E. R., Lovell, A., … Hay, D. L. (2020). Molecular mechanisms of class B GPCR activation: Insights from adrenomedullin receptors. ACS Pharmacology & Translational Science, 3(2), 246-262. doi: 10.1021/acsptsci.9b00083

Hendrikse, E. R., Liew, L. P., Bower, R. L., Bonnet, M., Jamaluddin, M. A., Prodan, N., … Hay, D. L. (2020). Identification of small-molecule positive modulators of calcitonin-like receptor-based receptors. ACS Pharmacology & Translational Science, 3(2), 305-320. doi: 10.1021/acsptsci.9b00108

Musa, H., Hendrikse, E. R., Brimble, M. A., Garelja, M. L., Watkins, H. A., Harris, P. W. R., & Hay, D. L. (2019). Pharmacological characterization and investigation of N-terminal loop amino acids of adrenomedullin 2 that are important for receptor activation. Biochemistry, 58(32), 3468-3474. doi: 10.1021/acs.biochem.9b00571

Yule, L. R., Garelja, M. L., Hendrikse, E. R., Gingell, J. J., Poyner, D. R., Harris, P. W. H., Brimble, M. A., & Hay, D. L. (2019). A potent fluorescent calcitonin gene-related peptide analogue enables visualization of receptor internalization. Peptide Science, 111(6), e2416. doi: 10.1002/pep2.24126

Alexander, S. P. H., Christopoulos, A., Davenport, A. P., Kelly, E., Mathie, A., Peters, J. A., … and CGTP Collaborators, including Hay, D. (2019). The concise guide to pharmacology 2019/2020. British Journal of Pharmacology, 176(Suppl. 1), S1-S493. doi: 10.1111/bph.14746

Hay, D. L., Garelja, M. L., Poyner, D. R., & Walker, C. S. (2018). Update on the pharmacology of calcitonin/CGRP family of peptides: IUPHAR Review 25. British Journal of Pharmacology, 175(1), 3-17. doi: 10.1111/bph.14075

Akter, R., Bower, R. L., Abedini, A., Schmidt, A. M., Hay, D. L., & Raleigh, D. P. (2018). Amyloidogenicity, cytotoxicity and receptor activity of bovine amylin: Implications for xenobiotic transplantation and the design of non-toxic amylin variants. ACS Chemical Biology, 13, 2747-2757. doi: 10.1021/acschembio.8b00690

Garelja, M. L., Walker, C. A., Siow, A., Yang, S. H., Harris, P. W. R., Brimble, M. A., … Hay, D. L. (2018). Receptor activity modifying proteins have limited effects on the class B G protein-coupled receptor calcitonin receptor-like receptor stalk. Biochemistry, 57(8), 1410-1422. doi: 10.1021/acs.biochem.7b01180

Dal Maso, E., Zhu, Y., Pham, V., Reynolds, C. A., Deganutti, G., Hick, C. A., … Hay, D. L., … Wootten, D. (2018). Extracellular loops 2 and 3 of the calcitonin receptor selectively modify agonist binding and efficacy. Biochemical Pharmacology, 150, 214-244. doi: 10.1016/j.bcp.2018.02.005

Walker, C. S., Raddant, A. C., Woolley, M. J., Russo, A. F., & Hay, D. L. (2018). CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured. Cephalagia, 38(3), 437-451. doi: 10.1177/0333102417691762

Liang, Y.-L., Khoshouei, M., Deganutti, G., Glukhova, A., Koole, C., Peat, T. S., … Hay, D. L., … Sexton, P. M. (2018). Cryo-EM structure of the active, Gs protein complexed, human CGRP receptor. Nature, 561(7724), 492-497. doi: 10.1038/s41586-018-0535-y

Booe, J. M., Warner, M. L., Roehrkasse, A. M., Hay, D. L., & Pioszak, A. A. (2018). Probing the mechanism of receptor activity-modifying protein modulation of GPCR ligand selectivity through rational design of potent adrenomedullin and calcitonin gene-related peptide antagonists. Molecular Pharmacology, 93(4), 355-367. doi: 10.1124/mol.117.110916

Alexander, S. P. H., Kelly, E., Marrion, N. V., Peters, J. A., Faccenda, E., Harding, S. D., … and CGTP Collaborators, including Hay, D. L. (2017). The concise guide to pharmacology 2017/18. British Journal of Pharmacology, 174(Suppl. 1), S1-S446. doi: 10.1111/bph.13987

Lee, S.-M., Booe, J. M., Gingell, J. J., Sjoelund, V., Hay, D. L., & Pioszak, A. A. (2017). N-glycosylation of asparagine 130 in the extracellular domain of the human calcitonin receptor significantly increases peptide hormone affinity. Biochemistry, 56(26), 3380-3393. doi: 10.1021/acs.biochem.7b00256

Woolley, M. J., Reynolds, C. A., Simms, J., Walker, C. S., Mobarec, J. C., Garelja, M. L., … Hay, D. L. (2017). Receptor activity-modifying protein dependent and independent activation mechanisms in the coupling of calcitonin gene-related peptide and adrenomedullin receptors to Gs. Biochemical Pharmacology, 142, 96-110. doi: 10.1016/j.bcp.2017.07.005

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Journal - Research Other

Gingell, J. J., Hendrikse, E. R., & Hay, D. L. (2019). New insights into the regulation of CGRP-family receptors. Trends in Pharmacological Sciences, 40(1), 71-83. doi: 10.1016/j.tips.2018.11.005

Hendrikse, E. R., Bower, R. L., Hay, D. L., & Walker, C. S. (2019). Molecular studies of CGRP and the CGRP family of peptides in the central nervous system. Cephalagia, 39(3), 403-419. doi: 10.1177/0333102418765787

Williams, E. T., Harris, P. W. R., Jamaluddin, M. A., Loomes, K. M., Hay, D. L., & Brimble, M. A. (2018). Solid-phase thiol–ene lipidation of peptides for the synthesis of a potent CGRP receptor antagonist. Angewandte Chemie International Edition, 57(36), 11640-11643. doi: 10.1002/anie.201805208

Hay, D. L. (2017). Amylin. Headache, 57(Suppl. 2), 89-96. doi: 10.1111/head.13077

Hay, D. L., & Walker, C. S. (2017). CGRP and its receptors. Headache, 57(4), 625-636. doi: 10.1111/head.13064

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