Jason Maynes

Novel Drug Targets for Heart Failure

Even with current therapeutic options, heart failure maintains a 50% five-year mortality rate. Using a combination of acquired patient heart tissue and cell and molecular models, we have discovered new therapeutic targets for cardiac dysfunction. This includes biophysical analysis of pertinent protein:protein interactions, drug screening, and the rational design of new therapeutic small molecules. Our work includes significant collaboration with industry/pharma, in particular for the design of new therapies targeting Integrin-linked kinase, and the pathogenic processes involved in heart/vascular fibrosis. We recently were part of an international collaborative team that described a new biomarker for heart failure. 

(a) Chung, S., Gouveia, Z., Shrestha, S., Coles, J. G., Maynes, J. T., and Santerre, J. P., (2025), Nanoparticles for the Delivery of Pro-regenerative Cardiac Progenitor Secretory Proteins Targeting Cellular Senescence and Vasculogenesis. ACS Appl. Bio Mater., doi:10.1021/acsabm.4c01361, Role: co-Principal Investigator. 
(b) Dou W, Shan G, Zhao Q, Malhi M, Jiang A, Zhang Z, González-Guerra A, Fu A, Law J,  Hamilton R, Bernal JA, Liu X, Sun Y, and Maynes JT, (2024), Identifying novel gap junction modifiers by robotic cardiomyocyte microinjection for arrhythmogenic cardiomyopathy, Science Robotics, doi:10.1126/scirobotics.adm8233, Role: Principal Investigator. 
(c) 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, Principal Investigator. 

Measurements of Cardiomyocyte Function

A significant limitation to the development of new pharmacologic options for cardiac dysfunction and heart failure is the lack of representative and translatable pre-clinical drug testing platforms. This gap in knowledge is additionally reflected in the high post-market withdrawal of drugs for unexpected cardiac toxicity. Utilizing iPSC-cardiomyocyte tissue, we have developed and tested platform technologies and algorithms that more accurately reflect the in vivo environment, allowing for disease modeling and the testing of new or existing drugs. 

(a) 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. 23, 2321–2331, Role: Principal Investigator. 
(b) Dou, W., Malhi, M., Cui, T., Wang, M., Wang, T., Shan, G., Law, J., Gong, Z., Plakhotnik, J., Filleter, T.,  Li, R., Simmons, C. A., Maynes, J. T., and Sun, Y. (2022) A Carbon-Based Biosensing Platform for Simultaneously Measuring the Contraction and Electrophysiology of iPSC-Cardiomyocyte Monolayers. ACS Nano. 16, 11278–11290, Role: Principal Investigator. 
(c) Dou, W., Wang, L., Malhi, M., Liu, H., Zhao, Q., Plakhotnik, J., Xu, Z., Huang, Z., Simmons, C. A.,  Maynes, J. T., and Sun, Y. (2021) A microdevice platform for characterizing the effect of mechanical strain magnitudes on the maturation of iPSC-Cardiomyocytes. Biosensors and Bioelectronics. 175, 112875. Role: Principal Investigator. 
(d) Wang, L., Dou, W., Malhi, M., Zhu, M., Liu, H., Plakhotnik, J., Xu, Z., Zhao, Q., Chen, J., Chen, S., Hamilton, R., Simmons, C. A., Maynes, J. T., and Sun, Y. (2018) Microdevice Platform for Continuous Measurement of Contractility, Beating Rate, and Beating Rhythm of Human-Induced Pluripotent Stem Cell-Cardiomyocytes inside a Controlled Incubator Environment. ACS Appl. Mater. Interfaces. 10, 21173–21183. Role: Principal Investigator. 

Cellular Mechanisms and Toxicities of Anesthetics

The pharmaceuticals commonly administered during anesthesia, necessarily, modulate neuronal activity, but may have effects that extend beyond the peri-operative period. This can manifest as changes to patient cognitive function, with undefined permanence (i.e., post-operative cognitive dysfunction). We have investigated the molecular, cellular, and patient factors that may contribute to adverse anesthetic effects, illustrating how gas anesthetics can alter mitochondrial form and function, protein folding, and ER function but do not appear to affect post-operative sleep patterns or long-term development in the pediatric population. 

(a) 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. Role: Principal Investigator. 
(b) O’Leary, J. D., Janus, M., Duku, E., Wijeysundera, D. N., To, T., Li, P., Maynes, J. T., Faraoni, D., and Crawford, M. W. (2018) Influence of Surgical Procedures and General Anesthesia on Child Development Before Primary School Entry Among Matched Sibling Pairs. JAMA Pediatr. 173, 29, Role: Co-Investigator. 
(c) Coghlan, M., Richards, E., Shaik, S., Rossi, P., Vanama, R. B., Ahmadi, S., Petroz, C., Crawford, M., and Maynes, J. T. (2018) Inhalational Anesthetics Induce Neuronal Protein Aggregation and Affect ER Trafficking. Sci Rep. 8, 5275, Role: Principal Investigator. 
(d) O’Leary, J. D., Janus, M., Duku, E., Wijeysundera, D. N., To, T., Li, P., Maynes, J. T., and Crawford, M.W. (2016) A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry. Anesthesiology. 125, 272–279, Role: Co-Investigator. 

Appointments, Cross Affiliations, Memberships 

Chief of Anesthesia and Pain Medicine at the Hospital for Sick Children. 
Associate Chief of Perioperative Services (Research) at the Hospital for Sick Children. 
Curtis Joseph and Harold Groves Chair in Anesthesia and Pain Medicine. 
Director of Research, Anesthesia and Pain Medicine 
Senior Scientist, Division of Molecular Structure and Function, SickKids Research Institute 
Adjunct Professor, Department of Biochemistry, University of Toronto 

Courses Taught 

BCH449H Medical Biochemistry
STF111 Structure and Function
MNU111 Metabolism and Nutrition