Toronto Lung Transplant Program's Research

Dr. Meghan Aversa obtained her MD from McGill University in 2011. Following residency training in Internal Medicine and Respirology at the University of Toronto, she completed a one-year combined fellowship in Pulmonary Hypertension and Lung Transplantation at Toronto General Hospital. She was an Assistant Professor in the Columbia University Medical Center Lung Transplant Program from 2017 to 2020 before returning to the Toronto Lung Transplant Program as a Respirologist and Clinician-Investigator. She earned her Masters of Science in Biostatistics from Columbia University's Mailman School of Public Health in 2021. Her clinical practice currently includes both pre- and post-lung transplant patients.

Chung-Wai Chow is a transplant respirologist at the Toronto Lung Transplant Program, Ajmera Multi-Organ Transplant Program, University Health Network. She completed her MD and PhD studies at the University of Toronto in Adult Respiratory Medicine and Cell Biology, respectively, before a Postdoctoral Fellowship in Molecular Cell Biology at the Max Planck Institute, Germany as an Alexander von Humboldt Fellow. She is a clinician-scientist in the Division of Respirology, Department of Medicine, Faculty of Medicine and is cross-appointed to the Dalla Lana School of Public Health and the Faculty of Applied Science & Engineering at the University of Toronto.

UHN Research Profile

Dr. Marcelo Cypel is a Staff Thoracic Surgeon at University Health Network (UHN), Senior-Scientist at the Toronto General Hospital Research Institute (TGHRI), and Professor of Surgery at the University of Toronto. He is the Surgical Director of the Ajmera Transplant Centre and the Surgical Director of the Artificial Lung Program at UHN. During his post-doctoral research fellowship at the Latner Thoracic Research Laboratories at TGHRI, he developed a new method of donor lung preservation and repair called Ex Vivo Lung Perfusion (EVLP). This method is now used clinically in Toronto and many other centres and has significantly increased the number of transplantable lungs. His main clinical and research interests are in artificial lung devices, EVLP, in vivo Lung Perfusion, and lung transplantation. He has secured substantial peer-reviewed funding, including the prestigious Tier 2 Canada Research Chair in Lung Transplantati on (Government of Canada). He is also the principal investigator of innovative clinical trials in Donation after Cardiac Death, localized chemotherapy to treat lung metastases and semi-elective lung transplantation.

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Dr. de Perrot's research focuses on innovative approaches to integrate immunotherapy with a short course of radiation and surgery for the treatment of mesothelioma. His work also focuses on the role of the immune system in the development of pulmonary hypertension, particularly in the context of pulmonary emboli. The surgical treatment of CTEPH with pulmonary thromboendarterectomy (PTE) performed at UHN provides unique opportunities to analyze this condition in the his laboratory. His laboratory has developed multiple experimental models to study the development and treatment of mesothelioma.

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Dr. Stephen Juvet is a clinician-scientist and lung transplant respirologist. After obtaining his MD, speciality training and PhD in Toronto, he pursued a postdoctoral research fellowship at the University of Oxford prior to his faculty appointment at UHN and the University of Toronto in 2015. He is involved in the care of patients with advanced lung disease before and after lung transplantation. His research interests include the mechanisms of chronic lung allograft dysfunction, and preventing allograft loss via strategies to promote immune tolerance. Another area of focus is the development of engineered tolerogenic cell therapies for use in transplantation.

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Dr. Golnaz Karoubi research interest is acute and chronic forms of lung disease remain major health care burdens and are expected to increase with an aging population. Altering the course of this intractable disease will require innovative and novel approaches to understand the underlying mechanisms of disease and develop therapeutic alternatives with a realistic path to clinical translation. The regenerative medicine landscape for the lung and trachea can be categorized into the following:

1. Cell-based therapeutic approaches for attenuation and/or abrogation of disease;
2. Ex vivo cell culture systems as platforms for disease modeling and therapeutics;
3. Tissue regeneration for replacement of damaged airway tissue.

Importantly, all of these approaches require practical numbers of functional therapeutic cells. We also need a thorough understanding of the cells and their function in their native and applied microenvironments. My research program is focused on the application of pluripotent stem cell sources in 'Airway Regeneration', balancing translational and exploratory approaches with the goal to better understand cell-microenvironment interactions. We seek to use the acquired information to develop and utilize physiologically relevant ex vivo platforms and thus engineer clinically applicable therapeutic strategies.

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Dr. Shaf Keshavjee is a world-renowned thoracic surgeon-scientist with a history of breakthroughs and discoveries in lung transplantation. He is the current Surgeon-in-Chief of the Sprott Department of Surgery, the Director of the Toronto Lung Transplant Program and Latner Thoracic Research Laboratories at UHN, and Professor of Thoracic Surgery at the University of Toronto.

Dr. Keshavjee completed his medical training at the University of Toronto in 1985, and specialized in General Surgery, Cardiac Surgery and Thoracic Surgery. He participated in the world's first successful double lung transplant at Toronto General Hospital in 1986. Dr. Keshavjee completed fellowships at Harvard University and the University of London. During his Master's studies, Dr. Keshavjee developed a lung preservation solution for donor lungs that has now been translated into clinical use around the world. Since then, he has led the development and translation of many innovations to the clinic, including the Ex Vivo Lung Perfusion (EVLP) system.

For Dr. Keshavjee's achievements and leadership in the field, he has been appointed as an Officer of the Order of Canada, the country's highest civilian honour that recognizes outstanding achievement, dedication to the community and service to the nation. Furthermore, he is a member of the Order of Ontario and has been awarded two Queen Elizabeth II Diamond Jubilee Medals. In 2020, he received the prestigious Governor General of Canada's Innovation Award. Other notable recognitions include UHN's Inventor of the Year Award, Canada's Top 40 Under 40, and the Lifetime Achievement Award from the Canadian Society of Transplantation.

UHN Research Profile

The major interest of our laboratory is the cellular and molecular mechanisms of acute lung injury in lung transplantation.

We are focusing on the ischemia-reperfusion induced lung injury in lung transplantation, especially on the role of different types of inflammation related programmed cell death. Bioinformatics, immunohistochemistry and ELISA are used to determine changes of cell death signals in patient plasma and in ex vivo lung perfusion (EVLP) perfusate. The results are correlated with clinical outcome to select biomarkers for donor lung assessment.

Another major research project is to develop new donor lung preservation solution and EVLP perfusion solution. Cell culture models are used for high throughput screening of components, concentrations and combinations of solution. Selected formulas are tested on animal lung transplantation and EVLP to determine improvement of donor lung function. The selected solution will be used to enable donor lung reconditioning (e.g., gene editing) and to improve clinical lung transplant outcome.

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Dr. Tereza Martinu is a lung transplant respirologist and clinician-scientist with the Toronto Lung Transplant Program. Dr. Martinu obtained her Medical Degree from McGill University in Montreal, Canada. She subsequently completed training in Internal and then Pulmonary and Critical Care Medicine at Duke University, in North Carolina, USA, before joining the Duke Lung Transplant Program. She was recruited to the Toronto program in August 2014. In her clinical time, Dr. Martinu cares for lung transplant patients and candidates with end-stage lung diseases. Her research studies focus on immunological and cellular mechanisms of chronic lung allograft dysfunction in humans as well as in animal models. Her goal is to develop improved diagnostic and therapeutic approaches for lung transplant patients with allograft dysfunction.

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Dr. Andrew T. Sage is an Assistant Scientist with the Toronto Lung Transplant Program at the Toronto General Hospital Research Institute and an Assistant Professor at the University of Toronto. Dr. Sage received a BSc (Biochemistry) from Queen's University in 2007, MSc from McMaster University (Biochemistry and Biomedical Sciences) in 2009, and a PhD from the University of Toronto (Pharmaceutical Sciences) in 2015. His research focuses on identifying and translating novel biomarkers and medical devices to aid in surgical decision-making during lung transplantation. He has a keen interest in cutting-edge technologies, including machine learning, artificial intelligence, and remote piloted aircrafts.

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Dr. Aman Sidhu is a Respirologist with the Toronto Lung Transplant Program and the Director of Quality and Innovation for the Ajmera Transplant Centre. She completed her medical school training at the University of Ottawa, followed by residency training in Internal Medicine at UBC, Respirology at the University of Alberta and finally a Lung Transplant fellowship at the University of Toronto. She holds an MSc in Epidemiology from the University of London, UK as well as additional training in clinical quality improvement. Aman's clinical practice includes pre and post-lung transplant care, as well as general respiratory medicine.

Her academic interests include improving the quality of care and patient experience in transplantation and lung disease. This includes work on the implementation and evaluation of innovative care delivery models using digital health technologies.

Research Interests:

• Xenotransplantation
• Leukocyte-endothelial cell interactions
• Endothelial cell activation and apoptosis

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Dr. Yasufuku is Professor of Surgery at the University of Toronto, Staff Thoracic Surgeon at the World prestige Division of Thoracic Surgery at Toronto General Hospital with special interest in minimally invasive diagnostics and therapeutics. He is the Director of the Interventional Thoracic Surgery Program at the University Health Network (UHN) which includes the Interventional Thoracic Surgery Animal OR capable of high end endoscopic development and the "state-of-the-art" Interventional Thoracic Surgery Suite at the Toronto General Hospital for clinical application of new developments. He is also the clinical lead of Thoracic Surgery within the GTx program within UHN. He is a Senior Scientist at the Latner Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, University Health Network and his research interests include development of new technology in early diagnosis and ultra-minimally invasive thoracic surgery, translational research in thoracic image guided therapeutics (GTx), nanotechnology enabled image guided intervention for lung cancer, and molecular profiling of advanced stage lung cancer by minimally invasive procedures.

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Dr. Jonathan Yeung is using modern genomic approaches to study diseases important to esophageal cancer and lung transplantation. For esophageal cancer, he is aiming to improve the personalization of treatment for patients by understanding the genetic makeup of each patient's tumors using an organoid model. For lung transplantation, he is aiming to develop the basic bioinformatic tools for the genomic study of transplantation.

UHN Research Profile