Research

Drug Discovery and Reverse Translation


Platform Leadership

Jane Foster, PhD
Francesco Leri, PhD

Active Sites

The Drug Discovery and Reverse Translation Platform operates at the following research sites:

  • St. Michael’s Hospital (Toronto, Ontario)
  • St. Joseph’s Healthcare Hamilton (Hamilton, Ontario)
  • University of Guelph (Guelph, Ontario)
  • University of Ottawa (Ottawa, Ontario)

Platform Overview

The Drug Discovery and Reverse Translation Platform tests clinical questions in preclinical settings to drive new findings. Animal models, including rodent and zebrafish models, are used to improve our understanding of the biological and behavioural underpinnings of depression and treatment response, and for drug discovery. For example, candidate microRNA biomarkers of antidepressant response identified by the CAN-BIND Molecular Platform have been used to develop fluorescent reporter zebrafish lines that will be used to screen for novel depression treatments. This is carried out in partnership with Janssen Pharmaceuticals and Canada’s first and only robotic, automated zebrafish high-throughput platform for drug discovery research. Researchers in this platform are also exploring how antidepressant medications from CAN-BIND clinical studies affect brain and behaviour in pre-clinical models, with the objective of uncovering key behavioural, electrophysiological and neurochemical mechanisms of depression.

 

Resources and Publications

 

Antidepressant drugs

Psychomotor effects of escitalopram plus aripiprazole in rats

Hudson, R., Zhou, Y., & Leri, F. (2017). The combination of escitalopram and aripiprazole: Investigation of psychomotor effects in rats. Journal of Psychopharmacology, 31(12), 1605-1614. doi:10.1177/0269881117732515

Buproprion and serotonin neuronal firing

El Mansari, M., Manta, S., Oosterhof, C., Iskandrani, K. S., Chenu, F., Shim, S., & Blier, P. (2014). Restoration of Serotonin Neuronal Firing Following Long-Term Administration of Bupropion but Not Paroxetine in Olfactory Bulbectomized Rats. International Journal of Neuropsychopharmacology, 18(4). doi:10.1093/ijnp/pyu050

 

Neural mechanisms of depression

Fatty acids and depression

Fernandes, M., Mutch, D., & Leri, F. (2017). The Relationship between Fatty Acids and Different Depression-Related Brain Regions, and Their Potential Role as Biomarkers of Response to Antidepressants. Nutrients, 9(3), 298. doi:10.3390/nu9030298

Monoamine system after stress

Oosterhof, C. A., Mansari, M. E., Merali, Z., & Blier, P. (2016). Altered monoamine system activities after prenatal and adult stress: A role for stress resilience? Brain Research, 1642, 409-418. doi:10.1016/j.brainres.2016.04.032

 

Depressive-like behaviours in pre-clinical models

Naltrexone and conditioned place avoidance

Daniels, S., Marshall, P., & Leri, F. (2015). Alterations of naltrexone-induced conditioned place avoidance by pre-exposure to high fructose corn syrup or heroin in Sprague–Dawley rats. Psychopharmacology, 233(3), 425-433. doi:10.1007/s00213-015-4121-9

Zebrafish models of depression (Review)
Fonseka, T. M., Wen, X., Foster, J. A., & Kennedy, S. H. (2015). Zebrafish models of major depressive disorders. Journal of Neuroscience Research, 94(1), 3-14. doi:10.1002/jnr.23639

Sugar self-administration in rats

Levy, A., Marshall, P., Zhou, Y., Kreek, M., Kent, K., Daniels, S., Shore, A., Downs, T., Fernandes, M.F., Mutch, D.M., Leri, F. (2015). Fructose:Glucose Ratios—A Study of Sugar Self-Administration and Associated Neural and Physiological Responses in the Rat. Nutrients, 7(5), 3869-3890. doi:10.3390/nu7053869

Operant intraoral self-administration in rats

Levy, A., Limebeer, C. L., Ferdinand, J., Shillingford, U., Parker, L. A., & Leri, F. (2014). A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration. Journal of Visualized Experiments, (84). doi:10.3791/50956