Picture of  Robert Laprairie

Robert Laprairie Assistant Professor

GSK-CIHR 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 the GlaxoSmithKline-CIHR chair in Drug Discovery and Development. He is a member of the Drug Discovery and Development Research Group (DDDRG) and the Cannabinoid Research Initiative of Saskatchewan (CRIS). He is the Director of Education for the Canadian Consortium for the Investigators of Cannabinoids (CCIC).  His teaching responsibilities include basic molecular pharmacology and neuroscience in the undergraduate and graduate Pharmacy programs. He is also involved in committee work with the Canadian Institutes of Health Research and the Animal Research Ethics Board of the University of Saskatchewan.

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 cannabis (e.g. THC and cannabidiol). CB1R is a potential target for the regulation of appetite and the treatment of pain, Huntington’s disease, and epilepsy 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 cannabis 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 cannabis as a medicine, and possibly lead to the development of new drug compounds.

Publications

Kovalchuk I, Pellino M, Rigault P, van Velzen R, Ebersbach J, Ashnest JR, Mau M, Schranz ME, Alcorn J, Laprairie RB, McKay JK, Burbridge C, Schneider D, Vergara D, Kane NC, Sharbel TF. The Genomics of Cannabis and Its Close Relatives. Annu Rev Plant Biol. 2020 Apr 29;71:713-739. doi: 10.1146/annurev- arplant-081519-040203. Epub 2020 Mar 10. PMID: 32155342.

Bagher AM, Young AP, Laprairie RB, Toguri JT, Kelly MEM, Denovan-Wright EM. Heteromer formation between cannabinoid type 1 and dopamine type 2 receptors is altered by combination cannabinoid and antipsychotic treatments. J Neurosci Res. 2020 Sep 2. doi: 10.1002/jnr.24716. Epub ahead of print. PMID: 32881145.

Cohen J, Wei Z, Phang J, Laprairie RB, Zhang Y. Cannabinoids as an Emerging Therapy for Posttraumatic Stress Disorder and Substance Use Disorders. J Clin Neurophysiol. 2020 Jan;37(1):28-34. doi: 10.1097/WNP.0000000000000612. PMID: 31895187.

Smolyakova AM, Zagzoog A, Brandt AL, Black T, Mohamed K, Laprairie RB. The Endocannabinoid System and Synthetic Cannabinoids in Preclinical Models of Seizure and Epilepsy. J Clin Neurophysiol. 2020 Jan;37(1):15-27. doi: 10.1097/WNP.0000000000000633. PMID: 31895186.

Garai S, Kulkarni PM, Schaffer PC, Leo LM, Brandt AL, Zagzoog A, Black T, Lin X, Hurst DP, Janero DR, Abood ME, Zimmowitch A, Straiker A, Pertwee RG, Kelly M, Szczesniak AM, Denovan-Wright EM, Mackie K, Hohmann AG, Reggio PH, Laprairie RB, Thakur GA. Application of Fluorine- and Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators. J Med Chem. 2020 Jan 23;63(2):542-568. doi: 10.1021/acs.jmedchem.9b01142. Epub 2020 Jan 3. PMID: 31756109; PMCID: PMC7077750.

Laprairie RB, Mohamed KA, Zagzoog A, Kelly MEM, Stevenson LA, Pertwee R, Denovan-Wright EM, Thakur GA. Indomethacin Enhances Type 1 Cannabinoid Receptor Signaling. Front Mol Neurosci. 2019 Oct 18;12:257. doi: 10.3389/fnmol.2019.00257. PMID: 31680861; PMCID: PMC6813218.

Laprairie RB, Vemuri K, Stahl EL, Korde A, Ho JH, Grim TW, Hua T, Wu Y, Stevens RC, Liu ZJ, Makriyannis A, Bohn LM. Probing the CB1 Cannabinoid Receptor Binding Pocket with AM6538, a High-Affinity Irreversible Antagonist. Mol Pharmacol. 2019 Nov;96(5):619-628. doi: 10.1124/mol.119.116483. Epub 2019 Sep 12. PMID: 31515283; PMCID: PMC6785652.

Laprairie RB, Bagher AM, Rourke JL, Zrein A, Cairns EA, Kelly MEM, Sinal CJ, Kulkarni PM, Thakur GA, Denovan-Wright EM. Positive allosteric modulation of the type 1 cannabinoid receptor reduces the signs and symptoms of Huntington's disease in the R6/2 mouse model. Neuropharmacology. 2019 Jun;151:1-12. doi: 10.1016/j.neuropharm.2019.03.033. Epub 2019 Mar 30. PMID: 30940536; PMCID: PMC6544167.

Toguri JT, Leishman E, Szczesniak AM, Laprairie RB, Oehler O, Straiker AJ, Kelly MEM, Bradshaw HB. Inflammation and CB2 signaling drive novel changes in the ocular lipidome and regulate immune cell activity in the eye. Prostaglandins Other Lipid Mediat. 2018 Nov;139:54-62. doi: 10.1016/j.prostaglandins.2018.09.004. Epub 2018 Sep 16. PMID: 30232034.

Grim TW, Park SJ, Schmid CL, Laprairie RB, Cameron M, Bohn LM. The effect of quinine in two bottle choice procedures in C57BL6 mice: Opioid preference, somatic withdrawal, and pharmacokinetic outcomes. Drug Alcohol Depend. 2018 Oct 1;191:195-202. doi: 10.1016/j.drugalcdep.2018.05.034. Epub 2018 Aug 2. PMID: 30138791; PMCID: PMC6317844.

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.