Dr Natasha Lillia Grimsey
PhD Pharmacology, BCom/BSc(Hons)
Dr Natasha Grimsey leads the G Protein-Coupled Receptor (GPCR) Molecular Pharmacology lab in the Department of Pharmacology and Clinical Pharmacology.
She holds a Sir Charles Hercus Health Research Fellowship (Health Research Council NZ), is a Principal Investigator of the Centre for Brain Research, and is an Associate Investigator of the Maurice Wilkins Centre for Molecular Biodiscovery.
Dr Grimsey is a University of Auckland graduate (BSc/BCom, Hons Biomedical Science, PhD Pharmacology 2010) who completed postdoctoral training under eminent molecular pharmacologist Professor Michelle Glass. Dr Grimsey's independent lab was established in 2016 and she has been awarded prestigious grants as principal investigator including a Marsden Fast-Start project grant, a Health Research Council Emerging Researcher First Grant, and an Auckland Medical Research Foundation Edith C. Coan Fellowship.
Natasha's research focuses on GPCR signalling and intracellular trafficking, with emphasis on the cannabinoid receptors and how these influence normal physiology and disease, as well as the development of quantitative assays utilising high-throughput techniques.
Research | Current
The G Protein-Coupled Receptor (GPCR) Molecular Pharmacology lab is interested in the fundamental mechanisms of GPCR function, both in normal and disease states, and how these fascinating proteins might be harnessed for therapeutic gain.
Our current focus is on Cannabinoid Receptor 2 (CB2). This is one of the receptors for the active components of Cannabis, however does not mediate the psychotropic effects of Cannabis. Rather, this receptor is primarily found in immune cells and thought to mediate immunosuppression. It is therefore hoped that targeting CB2 might be therapeutically useful in a wide range of disorders, including neuroinflammation (e.g. stroke, neurodegeneration), auto-immunity (e.g. multiple sclerosis), atherosclerosis, and various cancers. However, study of this receptor is in its infancy in comparison with many other GPCRs and there is still much to be learned about how this receptor functions at a fundamental level.
Current lines of inquiry include:
- Design and study of novel potential therapeutic drugs for activation or inhibition of specific signals via CB2 and/or target and detect different populations of CB2, in collaboration with Dr Andrea Vernall (University of Otago) and Dr Uwe Grether (Roche Pharmaceuticals, Switzerland).
- Investigating CB2 signalling and functional effects in human primary immune cells, in collaboration with Dr Scott Graham (University of Auckland) and Professor Rod Dunbar (University of Auckland).
- Determining how cannabinoid receptor signalling and subcellular distribution are controlled, including protein-protein interactions, in collaboration with Dr Christopher Walker (University of Auckland), Dr Kathy Mountjoy (Universtiy of Auckland) and Dr Darren Saunders (University of New South Wales, Australia).
- Comparison of CB2 function in different species; definition of the molecular mechanisms of human CB2 function and validation of preclinical models.
- Development and characterisation of ligands for Positron Emission Tomography (PET) imaging of CB2, in collaboration with Dr Muneer Ahamed (South Australian Health and Medical Research Institute, Australia).
- Assessing the activity of synthetic cannabinoids of abuse at CB2; project led by Professor Michelle Glass (University of Otago).
- Investigating biased signalling of Parathyroid Hormone Receptor 1 (PTH1R) for potential therapeutic application in osteoporosis with Dr Raewyn Poulsen (University of Auckland) and Dr Barbara Lipert (University of Auckland).
- Understanding melanocortin receptor signalling and impacts on lipid metabolism; project led by Dr Kathy Mountjoy (Universtiy of Auckland).
Techniques include: mammalian cell culture (cell lines and human primary immune cells), radioligand binding, signalling assays (lysate and real-time BRET/FRET and fluorescence biosensors), immunocytochemistry, widefield and confocal microscopy, high-throughput/content imaging and analysis, western blotting, bimolecular fluorescence complementation, cytometric bead array.
Teaching | Current
Enquiries from prospective graduate students and postdocs are welcome
Projects on offer: Please contact me - new project advertisement system coming soon, FindAPhD.com; other projects may also be available.
Carina Lee (2022, primary supervisor)
Raahul Sharma (2022, primary supervisor)
Emma Carruthers (2019, primary supervisor)
Zak Whiting (2019, primary supervisor)
Karren Wood (2019, primary supervisor)
Monica Patel (2018, co-supervisor)
Braden Woodhouse (2014, primary supervisor)
Karan Govindpani (2014, co-supervisor)
Summer students: Maddie Whiting (2021), Carina Lee (2020), Karren Wood (2019), Lauren Carlton (2019), Emma Carruthers (2018), Kate Velasco (2018), Samuel King (2014), David Finlay (2013), AJ Sykes (2008)
Intern: Madhurima Dhar (2020), Erica O'Beirne (2018)
Jules Devaux, Research Technician (2019 - 2020)
Nat Glenn, Research Assistant (2021)
Chevonne Linderboom, Research Technician (2016 - 2017)
Christa Macdonald, Research Technician (2018 - 2021)
Caitlin Oyagawa, Research Assistant (2020)
Areas of expertise
- Cannabinoid receptors 1 and 2 (CB1 & CB2)
- G-protein coupled receptor trafficking and signalling
- Receptor intracellular trafficking
- Molecular pharmacology
- Signalling biosensors
- High content analysis and high throughput screening
Selected publications and creative works (Research Outputs)
- Patel, M., Manning, J. J., Finlay, D. B., Javitch, J. A., Banister, S. D., Grimsey, N. L., & Glass, M. (2020). Signalling profiles of a structurally diverse panel of synthetic cannabinoid receptor agonists. Biochemical pharmacology, 17510.1016/j.bcp.2020.113871
- Gillis, A., Gondin, A. B., Kliewer, A., Sanchez, J., Lim, H. D., Alamein, C., ... Schmiedel, F. (2020). Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists. Science signaling, 13 (625).10.1126/scisignal.aaz3140
- Grimsey, N. L., Savinainen, J. R., Attili, B., & Ahamed, M. (2019). Regulating membrane lipid levels at the synapse by small-molecule inhibitors of monoacylglycerol lipase: new developments in therapeutic and PET imaging applications. Drug discovery today10.1016/j.drudis.2019.10.004
- Sachdev, S., Boyd, R., Grimsey, N. L., Santiago, M., & Connor, M. (2019). Brodifacoum does not modulate human cannabinoid receptor-mediated hyperpolarization of AtT20 cells or inhibition of adenylyl cyclase in HEK 293 cells. PEERJ, 710.7717/peerj.7733
- Singh, S., Oyagawa, C. R. M., Macdonald, C., Grimsey, N. L., Glass, M., & Vernall, A. J. (2019). Chromenopyrazole-based High Affinity, Selective Fluorescent Ligands for Cannabinoid Type 2 Receptor. ACS medicinal chemistry letters, 10 (2), 209-214. 10.1021/acsmedchemlett.8b00597
Other University of Auckland co-authors: Caitlin Oyagawa
- Saroz, Y., Kho, D. T., Glass, M., Graham, E. C., & Grimsey, N. L. (2019). Cannabinoid Receptor 2 (CB2) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes. ACS Pharmacology and Translational Science, 2 (6), 414-428. 10.1021/acsptsci.9b00049
Other University of Auckland co-authors: Scott Graham
- Ibsen, M. S., Finlay, D. B., Patel, M., Javitch, J. A., Glass, M., & Grimsey, N. L. (2019). Cannabinoid CB1 and CB2 Receptor-Mediated Arrestin Translocation: Species, Subtype, and Agonist-Dependence. Frontiers in pharmacology, 1010.3389/fphar.2019.00350
- Oyagawa, C. R. M., de la Harpe, S. M., Saroz, Y., Glass, M., Vernall, A. J., & Grimsey, N. L. (2018). Cannabinoid Receptor 2 Signalling Bias Elicited by 2,4,6-Trisubstituted 1,3,5-Triazines. Frontiers in Pharmacology, 9, 1202-1202. 10.3389/fphar.2018.01202
Other University of Auckland co-authors: Caitlin Oyagawa
Primary office location
M&HS BUILDING 503 - Bldg 503
Level 5, Room 501F
85 PARK RD