Research Streams

Basic Research

The Beazely lab interested in basic mechanisms of GPCR and growth factor signaling in neurons, and how these classes of receptors regulate ion channel signaling. Specifically, we focus on the interactions between 5-HT and dopamine receptors, platelet-derived growth factor (PDGF) receptors and TrkB, and NMDA receptors. This work will expand our understanding of neuronal function and dysfunction in mental health conditions including schizophrenia and depression, as well as susceptibility to addiction and substance use.

Substance Use Research

Dr. Beazely’s research includes the evaluation of undergraduate pharmacy education with respect to substance use and ongoing educational tool development for practicing health professionals. He is interested in assessing interventions by community pharmacists aimed at reducing harms associated with substance use and understanding the intersection between drug use and ongoing pharmaceutical care, and making community pharmacists leaders in harm reduction.

Ongoing Projects

Assessing pharmacy-based take-home naloxone (THN) programs and addressing gaps.

Despite being available without a prescription from pharmacies since 2016, and despite opioid-induced respiratory depression (OIRD) and opioid-associated deaths at an all time high, pharmacy THN programs are not being used to their maximum potential. In addition, there are provincial and regional disparities with respect to accessing naloxone and its dosage forms. We are assessing barriers to pharmacy THN distribution via scoping reviews and surveys and are creating and updated naloxone training program for pharmacists.

Short vs. longterm 5-HT7 receptor regulation of RTKs and NMDA receptor activity: implications for neuroprotection

Acute (5 min) activation of 5-HT7 receptors increases NMDA-evoked currents in isolated hippocampal neurons. Interestingly, long-term (2-24 h) exposure to 5-HT7 receptor agonists downregulates the NR1 and NR2B NMDA receptor subunits and upregulates the PDGFβ receptor, a negative regulator of NMDA receptor signaling, and TrkB, often associated as a positive regulator of NMDA receptorsignaling. Thus, thereis aretemporally different regulatory pathways of NMDA receptors after 5-HT7 receptor activation. We have recently demonstrated that 5-HT7 receptor activation was able to protect hippocampal neurons against NMDA-induced excitotoxicity via its ability to increasePDGFβ receptorsignalling.

Receptor tyrosine kinase transactivation by GPCRs and the heterologous desensitization of transactivation

Application of 5-HT to primary cortical neurons or SH-SY5Y results in the transactivation of the PDGFβ receptor and TrkB. Many of the intracellular signaling steps in this pathway are similar to other transactivation pathways. However an interesting difference is that in this system compared to other transactivation pathways is that ERK1/2 phosphorylation is not dependent upon transactivation of the RTK. We recently demonstrated that such GPCR-RTK pathways can undergo a desensitization process.

Transactivated vs. ligand-activated RTKs

There is a growing number of examples of GPCR-RTK transactivation pathways. We are taking a step back and asking some fundamental questions about transactivation. Is a transactivated RTK the same as a ligand-activated RTK? Are the same tyrosine residues phosphorylated? Is the magnitude of transactivation sufficient to initiate signaling events (often the maximal increase in tyrosine phosphorylation is 2-3 fold, compared to up to 100 fold increases with ligands)?

Current Research Support

2020-2021, Interdisciplinary Seed Grant (UW Pharmacy), “Intersectionality between clinical and sociodemographic factors in the influence on the relationship between use of codeine, meperidine and morphine-containing medications and opioid-related morbidity and mor-tality after surgery in the Canadian population from 2000-2017 “ (co-PI)

2019-2024, NSERC Discovery Grant, “Receptor Tyrosine Kinase Transactivation in Neuronal Signalling, Survival, and Stress” (PI)

2019-2021, Substance Use and Addictions Program, Health Canada, “Scaling Up National

Substance Use Education for Primary Care Clinicians and Community Partners” (Co-PI)

2019-present, Network for Aging Research, Catalyst Grant, “Changes in neuronal cellular mem-brane composition in aging and Alzheimer's disease” (co-PI)

2019-present, Dean’s Undergraduate Teaching Initiative, Faculty of Science, “Integrating and Evaluating Active Learning in Clinical Skills-Based Courses” (Co-Investigator)

Recent Publications

Cid A, Daskalakis G, Grindrod K, Beazely MA. What Is Known about Community Pharmacy-Based Take-Home Naloxone Programs and Program Interventions? A Scoping Review.Pharmacy. 2021; 9(1):30.

Robinson M, Lou J, Mehrazma B, Rauk A, Beazely M, Leonenko Z. Pseudopeptide Amyloid Aggregation Inhibitors: In Silico, Single Molecule and Cell Viability Studies. Int J Mol Sci. 2021;22:1051.

Gondora N, Sanyal C, Carter C, Nethercott A, Sproule B, Turcotte D, Halpape K, Bishop LD, Nissen L, Beazely MA, Kwong M, Versteeg S, Chang F. The role of pharmacists in opi-oid stewardship: Protocol. Res Soc Admin Pharm. 2020

So R, Al Hamarneh Y, Barnes M, Beazely MA, Boivin M, Laroche J, Patel H, Sihot A, Smith T, Tsuyuki RT. The status of naloxone in community pharmacies across Canada. Can Pharm J (Ott). 2020;153:352-6. doi: 10.1177/1715163520958435.

Tsuyuki RT, Arora V, Barnes M, Beazely MA, Boivin M, Chrisofides A, Patel H, Laroche J,

Sihota A, So R. Canadian national consensus guidelines for naloxone prescribing by pharmacists. Can Pharm J (Ott). 2020;153:347-51. doi: 10.1177/1715163520949973.

Vasefi MS and Beazely MA. Neuroprotective effects of direct activation and transactivation of PDGFbeta receptors. Vessel Plus, In Press

Lai D, Pham AT, Nekkar Rao PP, Beazely MA. The effects of heat and freeze-thaw cycling on naloxone stability. Harm Reduct J. 2019;16:17.

Liu H, Saffi GT, Vasefi MS, Choi Y, Kruk JS, Ahmed N, Gondora N, Mielke J, Leonenko Z, Beazely MA. Amyloid-beta inhibits PDGFbeta receptor activation and prevents PDGF-BB-induced neuroprotection. Curr Alzheimer Res. 2018 Epub Jan 9 2018.

Grindrod K and Beazely MA. Fitting Naloxone into community practice. Can Pharm J (Ott). 2016 Nov;149(6):329-331. This article was adapted and reproduced in the Spanish pharmacy journal el Farmaceutico.

Recent Posters and Presentations:

2020, Abstract, “Embedding an accredited cannabis module within an upper-year therapeutics course”, AFPC Conference (abstracts published in the Canadian Pharmacists Journal)

2020, Invited Seminar, Cannabis Use in Older Adults, Coalition of Pharmacists Caring for Aging Canadians, National Conference, Online

2020, Invited Seminar, Cannabis Edibles, Efficacy, and Special Populations, Canadian Nutrition Society, Monthly Webinar

2020, Community Talk, Cannabis and Brain Injury, Waterloo-Wellington Brain Injury Associa-tion (Guelph, Kitchener, Arthur)

2019, Invited Seminar, Medical, Recreational, or Both? What is my Role on the Front Lines of Cannabis Use, Walmart Pharmacy Conference, Toronto, ON

2019, Invited Seminar, Pharmacology of Cannabis, Regional Hospital Pharmacy Technician Conference, Kitchener, ON

2019, Seminar, Expert Witness Symposium, Ontario Association of Chiefs of Police, Opioid Pharmacology

2019, Seminar, Waterloo Pharmacy Reunion Weekend, Cannabis Edibles: What Pharmacists need to know

2019, Invited Webinar, Pharmacology of Cannabis: The Endocannabinoid System and the Role of Cannabinoids in the Body, Canadian Mental Health Association - Waterloo-Welling-ton, Via Ontario Telemedicine Network

2018, Invited Seminar, Illicit Substance Use: Understanding the impact on medication management and opportunities for harm reduction, Ontario Pharmacists Association, Huntsville, ON

2018, Seminar, with trainee Nyasha Gondora, Molecular Mechanisms of Stress, Drug Safety and Effectiveness Cross-Disciplinary Program Conference, Toronto

2017, Seminar, Cannabis Basics for Clinicians, Guelph Pharmacists Association

2017, Invited Webinar, Street Fentanyls: What Pharmacists Need to Know, Canadian Pharmacists Association, (over 180 pharmacists across Canada watched live, an additional 170 downloaded the video and resources)

2017, Seminar, Opioids, Fentanyls, Overdose, and Naloxone, Grand River Hospital Technicians Conference, Kitchener, ON

2017, Seminar, “Opioid overdose and naloxone - what parents and caregivers need to know” Public Lecture, School of Pharmacy, University of Waterloo

2017, Seminar, “Opioid overdose and naloxone in community pharmacy practice” McKesson Showcase, Toronto

2017, Seminar, “Opioid overdose and naloxone in primary care” PriMed Conference, Toronto

2017, Seminar, “Opioid overdose, naloxone, and opioid prescribing” Expert Witnesses in Drug Trials Conference, Toronto

2016, Seminar, “The Opioid Crisis”. School of Pharmacy, University of Waterloo, Public Lecture

2016, Seminar, “An emerging role for 5-HT7 receptors as a therapeutic target: focus on growth factor receptor cross-talk” Department of Psychology, Brock University

2016, Seminar, “Opioid Overdose and Naloxone” Ontario Association of Chiefs of Police Conference, Toronto

2016, Seminar, “Indirect activation of receptor tyrosine kinases (RTKs) in neurodegeneration and psychiatric disease” Soochow University, Suzhou, China

Michael Beazely 2016