Dr Natasha Lillia Grimsey

PhD Pharmacology, BCom/BSc(Hons)

Biography

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 Affiliate 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.

Publications: Google ScholarNCBI

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:

  • Learning more about CB2 function via the design and study of novel potential therapeutic drugs with potential to activate or inhibit specific signals via CB2 and/or target different populations of CB2, in collaboration with Dr Andrea Vernall (University of Otago).
  • Investigating CB2 signalling and functional effects in primary human immune cells, in collaboration with Dr Scott Graham (School of Medical Sciences and Centre for Brain Research, University of Auckland) and Professor Rod Dunbar (School of Biological Sciences and Maurice Wilkins Centre, University of Auckland).
  • Determining how the subcellular distribution of CB2 is controlled, including the protein-protein interactions responsible (which might in themselves represent novel therapeutic targets), in collaboration with Dr Darren Saunders (University of New South Wales, Australia).
  • Comparison of CB2 function in different species, which assists in defining the molecular mechanisms of human CB2 function and is particularly important for validation of preclinical models.
  • Development and characterisation of ligands for Positron Emission Tomography (PET) imaging of CB2, in collaboration with Dr Muneer Ahamed (University of Queensland, Australia).

Techniques include: mammalian cell culture (cell lines and primary human immune cells), radioligand binding, signalling assays (lysate and real-time RET and fluorescence biosensors), immunocytochemistry, widefield and confocal microscopy, high-throughput/content imaging and analysis, western blotting, bimolecular fluorescence complementation, cytometric bead array.

Publications: Google ScholarNCBI

Enquiries from prospective graduate students and postdocs are welcome
Projects on offer: UoA FindAThesisFindAPhD.com; other projects may also be availabe.

Teaching | Current

Lecturing:
- MEDSCI204 Pharmacology & Toxicology
- MEDSCI304 Molecular Pharmacology

Postgraduate supervision

Enquiries from prospective graduate students and postdocs are welcome
Projects on offer: UoA FindAThesisFindAPhD.com; other projects may also be availabe.

Current Students

Caitlin Oyagawa (PhD primary supervisor)
Emma Carruthers (PhD primary supervisor)
Shree Kumar (PhD co-supervisor)
Madhurima Dhar (Masters primary supervisor)
Nat Glenn (Masters primary supervisor)
Monica Patel (PhD advisor)

Current Staff

Christa Macdonald, Research Technician (2018 - current)
Caitlin Oyagawa, Research Assistant (2020)


Completed Students

PhD
David Finlay (2018, co-supervisor)
Morag Hunter (2015, co-supervisor)

Masters
Caitlin Oyagawa (2016, primary supervisor)
David Finlay (2014, co-supervisor)

Honours
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: Karren Wood (2019), Lauren Carlton (2019), Emma Carruthers (2018), Kate Velasco (2018), Samuel King (2014), David Finlay (2013), AJ Sykes (2008)
Intern: Erica O'Beirne (2018)

Prior Staff

Chevonne Linderboom, Research Technician (2016 - 2017)
Jules Devaux, Research Technician (2019 - 2020)

Areas of expertise

  • Cannabinoids
  • Cannabinoid receptors 1 and 2 (CB1 & CB2)
  • G-protein coupled receptor trafficking and signalling
  • Receptor intracellular trafficking
  • Molecular pharmacology
  • Neuropharmacology
  • Signalling biosensors
  • High content analysis and high throughput screening

Selected publications and creative works (Research Outputs)

  • 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
  • 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, online first10.1021/acsptsci.9b00049
    Other University of Auckland co-authors: Michelle Glass, Scott Graham
  • Waters, S., Dieriks, B., Swanson, M., Zhang, Y., Grimsey, N., Murray, H., ... An, J. (2019). Blood-spinal cord barrier leakage is independent of motor neuron pathology in ALS. 10.1101/704270
    Other University of Auckland co-authors: Henry Waldvogel, Helen Murray
  • 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
    URL: http://hdl.handle.net/2292/46072
    Other University of Auckland co-authors: Caitlin Oyagawa, Michelle Glass
  • 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
    URL: http://hdl.handle.net/2292/46927
    Other University of Auckland co-authors: Michelle Glass
  • 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
    URL: http://hdl.handle.net/2292/45757
    Other University of Auckland co-authors: Caitlin Oyagawa, Michelle Glass
  • Cooper, A. G., Oyagawa, C. R. M., Manning, J. J., Singh, S., Hook, S., Grimsey, N. L., ... Vernall, A. J. (2018). Development of selective, fluorescent cannabinoid type 2 receptor ligands based on a 1,8-naphthyridin-2-(1H)-one-3-carboxamide scaffold. MedChemComm10.1039/C8MD00448J
    URL: http://hdl.handle.net/2292/45906
    Other University of Auckland co-authors: Caitlin Oyagawa, Michelle Glass
  • Finlay, D., Cawston, E., Grimsey, N., Hunter, M., Korde, A., Vemuri, V., ... Glass, M. (2017). Gαs signalling of the CB₁ receptor and the influence of receptor number. British Journal of Pharmacology, 174 (15), 2545-2562. 10.1111/bph.13866
    URL: http://hdl.handle.net/2292/35307
    Other University of Auckland co-authors: Michelle Glass, Erin Cawston

Identifiers

Contact details

Primary office location

M&HS BUILDING 503 - Bldg 503
Level 5, Room 501
85 PARK RD
GRAFTON
AUCKLAND 1023
New Zealand

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