Shaf Keshavjee, MD, MSc, FRCSC, FACS

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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 is a global leader in lung transplantation—a life-saving intervention for patients with end-stage lung disease. However, there still remains a vastly insufficient supply of suitable donor organs to meet current and future transplantation needs. Our multidisciplinary research team is part the Latner Thoracic Research Laboratories, a clinical and research program that aims to revolutionize how the world performs lung transplantation. My research group focuses on the molecular mechanisms of lung preservation, injury and repair. Our projects include a focus on precision diagnostics, therapeutics, stem cell therapies, CRISPR gene regulation and novel methods of tissue and whole organ preservation.

Our group has attracted international recognition for our Ex Vivo Lung Perfusion (EVLP) system, a pioneering technology that enables us to objectively assess donor lungs outside of the body prior to transplantation. Importantly, we can use this system to enable therapies that actually repair damaged lungs. Since our first clinical trial in 2008, EVLP has dramatically increased donor utilization rates and significantly improved recipient outcomes.

We have leveraged EVLP to develop several diagnostic platforms that measure lung injury and can predict a patient’s trajectory following transplantation. Our TORdx LUNG™ diagnostic measures inflammatory biomarkers and produces a lung “score” that accurately determines the suitability of donor lungs for transplantation. Similarly, our RALI-Dx™ (Rapid Acute Lung Injury Diagnostic) assay measures biomarkers to predict the severity of upper respiratory infection and viral infection, helping to accurately triage patients into the appropriate care. We used RALI-Dx™ in one of UHN’s largest COVID-19 research studies to predict the severity of COVID-19 infection.

In addition, we are researching novel repair therapies to prevent organ rejection and dramatically reduce post-transplant morbidity and mortality. These therapies include alpha-1 antitrypsin (A1AT) and regulatory T cell therapy. Our research shows that A1AT has excellent potential to reduce ischemia reperfusion injury and primary graft dysfunction, which are two of the most prevalent post-transplant complications. With industry support, we are set to begin a Phase I prospective randomized controlled trial to use A1AT in human lung transplantation.

We have also found that CD4+CD25+FOXP3+ regulatory T cells (Tregs) play a critical role in establishing immunological tolerance in lung transplant recipients and preventing the development of chronic lung allograft dysfunction (CLAD), the primary cause of post-transplant mortality.

Finally, we are researching CRISPR/Cas9-based transcriptional gene activation of IL-10—a critical anti-inflammatory cytokine that can significantly improve lung transplant outcomes. Our promising results thus far advance the possibility of creating epigenetically modified donor organs.

Ultimately, our goal at the Latner Labs is to continue to translate our research findings to the clinic, eliminate the transplant waitlist and ensure that donor lungs are available to all in need.

For a list of Dr. Keshavjee's publications, please visit PubMed, Scopus or ORCID.

 

Recent Publications

Kanou T, Nakahira K, Choi AM, Yeung JC, Cypel M, Liu M, Keshavjee S. Cell-free DNA in human ex vivo lung perfusate as a potential biomarker to predict the risk of primary graft dysfunction in lung transplantation. J Thorac Cardiovasc Surg. 2020 Aug 11: S0022-5223.

Cypel M, Keshavjee S. When to consider lung transplantation for COVID-19. Lancet Respir Med. 2020 Oct;8(10):944-946.

Elmi M, Wakeam E, Azin A, Presutti R, McCready DR, Cil TD, Keshavjee S. Surgical Morbidity of Full-Thickness Chest Wall Resection for Breast Cancer: A Retrospective Study of a National Database. J Surg Res. 2021 Jan;257:161-166.

Yeung JC, Machuca TN, Chaparro C, Cypel M, Stephenson AL, Solomon M, Saito T, Binnie M, Chow CW, Grasemann H, Pierre AF, Yasufuku K, de Perrot M, Donahoe LL, Tikkanen J, Martinu T, Waddell TK, Tullis E, Singer LG, Keshavjee S. Lung transplantation for cystic fibrosis. J Heart Lung Transplant. 2020 Jun;39(6):553-560.

Waddell TK, Tullis E, Singer LG, Keshavjee S. Lung transplantation for cystic fibrosis. J Heart Lung Transplant. 2020 Jun;39(6):553-560.


Surgeon-in-Chief, Sprott Surgery, University Health Network
James Wallace McCutcheon Chair in Surgery, University Health Network
Director, Toronto Lung Transplant Program
Director, Latner Thoracic Research Laboratories
Professor, Department of Surgery, University of Toronto
Vice Chair of Innovation, Department of Surgery, University of Toronto
Cross Appointed Faculty, Institute of Biomedical Engineering, University of Toronto