Dr. Jason Maynes

Lab Description

Dr. Maynes's laboratory is located in the Department of Anesthesia and Pain Medicine Hospital for Sick Children. He has 14 current lab members including research associates, technicians, graduate students and clinical fellows. The lab has over 40 collaborators including clinicians, surgeons, epidemiologists, engineers and basic scientists. The lab reserach focuses on three main areas that attempt to combine Dr. Maynes's clinical training in paediatrics and anaesthesia with his research training in biophysics: (1) the mechanism of anaesthetic action and anaesthetic off-targets, (2) proteins involved in mitochondrial dynamics and, (3) high-content imaging and image analysis. Methodologies span all spectrums, including X-ray crystallography, NMR, mammalian cell protein expression, fluorescence spectroscopy, high-resolution fluorescence imaging, high-content imaging, robotics, micro-injection, stem cell models, and animal models.

Research Focus

In a broad, overarching theme, the Maynes lab focuses on investigating mechanisms of drug toxicity and damage. Much of the unpredictability of drug toxicity is due to inadequate pre-clinical models to identify cellular dysfunction that would require massive numbers to identify in Stage III/IV clinical trials, owing to the potential diversity of the clinical phenotype resulting from the underlying toxicity being observed on a whole-organism scale. This concept leads to another key issue with drug toxicity, specifically the development of assays to measure cellular dysfunction in more complex systems than at the single enzyme level, taking into consideration the cellular ecosystem using a systems biology approach. Mitochondria are the primary metabolic organelles in the cell and also play important roles in modulating cell health including when to induce cell death via several different pathways. This organelle then is often a key component of drug toxicity. The lab addresses these concepts by looking at new models and assays to predict toxicity (including the use of stem-cell derived tissues), and investigating fundamental concepts in mitochondrial form, function and health. Researchers in the Maynes Lab are working to link current concepts and problems in clinical medicine with research techniques to form an active translational medicine research program.

Selected Publications 

1. Plakhotnik, J., Zhang, L., Estrada, M., Coles, J. G., Lonnqvist, P.-A., and Maynes, J. T. (2022) Local Anesthetic Cardiac Toxicity Is Mediated by Cardiomyocyte Calcium Dynamics. Anesthesiology. 137, 687–703
2. Hogarth, K., Vanama, R. B., Stratmann, G., and Maynes, J. T. (2021) Singular and short-term anesthesia exposure in the developing brain induces persistent neuronal changes consistent with chronic neurodegenerative disease. Sci Rep. 11, 5673
3. Dou, W., Daoud, A., Chen, X., Wang, T., Malhi, M., Gong, Z., Mirshafiei, F., Zhu, M., Shan, G., Huang, X., Maynes, J. T., and Sun, Y. (2023) Ultrathin and Flexible Bioelectronic Arrays for Functional Measurement of iPSC-Cardiomyocytes under Cardiotropic Drug Administration and Controlled Microenvironments. Nano Lett. 10.1021/acs.nanolett.3c00017
4. Toyama, Y., Harkness, R. W., Lee, T. Y. T., Maynes, J. T., and Kay, L. E. (2021) Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR. Proc Natl Acad Sci USA. 118, e2025022118
5. Diskin, C., Orkin, J., Dharmaraj, B., Agarwal, T., Parmar, A., McNaughton, K., Cohen, E., Sunderji, A., Faraoni, D., Fecteau, A., Fischer, J., Maynes, J., Mahant, S., and Friedman, J. (2023) Secondary impacts of the COVID-19 pandemic at a tertiary children’s hospital in Canada: a mixed-methods study. BMJ Open. 13, e059849, doi: 10.1136/bmjopen-2021-059849.