Picture of  Robert Laprairie

Robert Laprairie Assistant Professor, Saskatchewan-GlaxoSmithKline Research Chair in Drug Discovery and Development

Address
3B36 Health Sciences

Education

  • BSc. Hon. Biochemistry – University of Saskatchewan (2010)
  • MSc. Pharmacology & Neuroscience – Dalhousie University (2012)
  • PhD Pharmacology – Dalhousie University (2016)
  • Postdoctoral fellowship – The Scripps Research Institute, Florida (2017)

Bio

Dr. Laprairie is a member of the Drug Discovery and Development Research Group and the Cannabinoid Research Initiative of Saskatchewan (CRIS). He is a member of the Canadian Society for Pharmacology and Therapeutics (CSPT), the Canadian Consortium for the Investigators of Cannabinoids (CCIC), the American Society for Pharmacology and Experimental Therapeutics (ASPET), and the International Cannabinoids Research Society (ICRS). 

Research

Dr. Laprairie’s research focuses on the endocannabinoid system and specifically the type 1 cannabinoid receptor (CB1R). CB1R is activated by the body’s own cannabinoids, synthetic cannabinoids, and cannabinoids from marijuana (e.g. THC and cannabidiol). CB1R is a potential target for the regulation of appetite and the treatment of pain, spasticity in multiple sclerosis, Huntington’s disease, epilepsy, and anxiety, among others. Despite its potential as a therapeutic target, we are still learning how CB1R is regulated by cannabinoids to alter physiology. His laboratory is working to (1) understand how the many different cannabinoids from marijuana affect CB1R function; and (2) develop new compounds known as allosteric modulators that increase or decrease CB1R activity. Dr. Laprairie’s research utilizes molecular biology, cell culture and animal models to study the endocannabinoid system in an attempt to further our understanding of marijuana as a medicine, and possibly lead to the development of new drug compounds.

Publications

Bagher AM, Laprairie RB, Kelly MEM, Denovan-Wright EM (2016). Bidirectional allosteric interactions between cannabinoid receptor 1 (CB1) and the dopamine receptor 2 long (D2L) heterotetramers. Eur J Pharmacol. In press.

Laprairie RB, Stahl EL, Bohn LM (2017). Approaches to assess biased signalling as the CB1R receptor. Cannabinoids and their Receptors. Methods in Enzymology Springer Protocols Humana Press. In press. Ed. Reggio PH.

Hua T, Vemuri K, Nikas SP, Laprairie RB, Wu Y, Qu L, Pu M, Korde A, Jiang S, Ho JH, Han GW, Ding K, Li X, Liu H, Hanson MA, Zhao S, Bohn LM, Makriyannis A, Stevens RC, Liu ZJ (2017). Crystal structures of agonist-bound human cannabinoid receptor CB1. Nature. doi: 10.1038/nature23272.

Laprairie RB, Kulkarni PM, Deschamps JR, Kelly ME, Janero DR, Cascio MG, Stevenson LA, Pertwee RG, Kenakin T, Denovan-Wright EM, Thakur GA (2017). Enantiospecific Allosteric Modulation of CB1 Cannabinoid Receptor. ACS Chem Neurosci. 8: 1188-1203.

Laprairie RB, Bagher AM, Denovan-Wright EM (2016). Cannabinoid receptor ligand bias: implications in the central nervous system. Curr Opin Pharmacol. 32: 32-43.

Hua T, Vemuri K, Pu M, Qu L, Han GW, Wu Y, Zhao S, Shui W, Li S, Korde A, Laprairie RB, Stahl EL, Zvonok N, Zhou H, Kufareva I, Hanson MA, Bohn LM, Makriyannis AM, Stevens RC, Liu Z-J (2016). Crystal structure of the human cannabinoid receptor CB1. Cell. 167: 750-762.

Laprairie RB, Denovan-Wright EM, Wright JM (2016). Subfunctionalization of peroxisome proliferator response elements accounts for retention of duplicated fabp1 genes in zebrafish. BMC Evol Biol. 16: 147.

Laprairie RB, Denovan-Wright EM, Wright JM (2016). Divergent evolution of cis-acting peroxisome proliferator-activated receptor elements that differentially control the tandemly-duplicated fatty acid-binding protein genes, fabp1b.1 and fabp1b.2, in zebrafish. Genome. 25: 1-10.

Bagher AM, Laprairie RB, Kelly ME, Denovan-Wright EM (2016). Antagonism of dopamine receptor 2 long (D2L) affects cannabinoid receptor 1 (CB1) signaling in a cell culture model of striatal medium spiny projection neurons. Mol Pharmacol. 89: 652-666.

Laprairie RB, Kulkarni AR, Kulkarni PM, Hurst DP, Lynch DL, Reggio PH, Janero DR, Pertwee RG, Stevenson LA, Kelly M, Denovan-Wright EM, Thakur GA (2016). Mapping cannabinoid receptor 1 allosteric site(s): critical molecular determinant and signaling profile of GAT100 – a novel, potent and irreversibly binding probe. ACS Chem Neurosci. 7: 776-798.

Laprairie RB, Bagher AM, Kelly ME, Denovan-Wright EM. (2016). Biased type 1 cannabinoid receptor signaling influences neuronal viability in a cell culture model of Huntington disease. Mol Pharmacol. 89: 364-375.

Kulkarni PM, Kulkarni AR, Korde A, Tichkule RB, Laprairie RB, Denovan-Wright EM, Zhou H, Janero DR, Zvonok N, Makriyannis A, Cascio MG, Pertwee RG, Thakur GA. (2015). Novel Electrophilic and Photoaffinity Covalent Probes for Mapping the Cannabinoid 1 Receptor Allosteric Site(s). J Med Chem. 59: 44-60.

Laprairie RB, Bagher AM, Kelly MEM, Denovan-Wright EM (2015). Cannabidiol is a negative allosteric modulator of the type 1 cannabinoid receptor. Br J Pharmacol. 172: 4790-4805.

Laprairie RB, Bagher AM, Precious SV, Denovan-Wright EM (2014). Components of the Endocannabinoid and Dopamine Systems are Dysregulated in Huntington’s Disease: Analysis of Publicly Available Microarray Datasets. Pharmacol Res & Persp. 3: e00104.

Laprairie RB, Bagher AM, Dupré DJ, Kelly MEM, Denovan-Wright EM (2014). Type 1 Cannabinoid Receptor Ligands Display Functional Selectivity in a Cell Culture Model of Striatal Medium Spiny Projection Neurons. J Biol Chem. 289: 24845-24862.

Laprairie RB, Warford JR, Hutchings S, Robertson GS, Kelly MEM, Denovan-Wright EM (2013). The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington’s disease and in striatal tissue from Huntington’s disease patients. J Neuroimmunol 267: 61-72.

Toguri JT, Lehmann C, Laprairie RB, Szczesniak AM, Zhou J, Denovan-Wright EM, Kelly MEM (2013). Anti-inflammatory effects of Cannabinoid 2 receptor activation in endotoxin-induced uveitis. Br J Pharmacol 171: 1448-1461.

Bagher AM, Laprairie RB, Kelly MEM, Denovan-Wright EM (2013). Co-expression of the human cannabinoid receptor coding region splice variants (hCB1) affects the function of hCB1 receptor complexes. Eur J Pharmacol 721: 341-354.

Laprairie RB, Kelly MEM, Denovan-Wright EM (2013). Cannabinoids induce type 1 cannabinoid receptor expression in cell culture models of striatal neurons: implications for Huntington’s disease. Neuropharmacol 72: 47 – 57.

Laprairie RB, Kelly MEM, Denovan-Wright EM (2012). The dynamic nature of type 1 cannabinoid receptor (CB1) gene transcription. Br J Pharmacol 167: 1583-1595.

Hogel M, Laprairie RB, Denovan-Wright EM (2012). Promoters are differentially sensitive to N-terminal mutant huntingtin-mediated transcriptional repression. PLoS One 7: e411152.