Jonathan Cools-Lartigue

December 2015

  • Residency Program: McGill University
  • Supervisors: Lorenzo Ferri MD PhD,

Personal statement:

Jonathan is currently completing his fifth year of surgical residency in the department of General Surgery at McGill University. After completion of his general surgery training, I will pursue a fellowship in cardiothoracic surgery at Memorial Sloan Kettering in New York. During his training, he has remained active in both clinical and basic scientific research. In particular, he is currently in the process of completing a PhD in Experimental surgery through the Surgeon Scientist Program at McGill University under the supervision of Dr. Lorenzo Ferri. His research interests are focused in the field of thoracic oncology as reflected in numerous publications in both the clinical and basic research domains. His PhD thesis has focused primarily on elucidating the mechanisms by which systemic inflammation promotes tumor progression in patients with lung and esophageal malignancies. In particular, this work has contributed greatly to the understanding of the role of neutrophil extracellular traps in circulating tumor cell sequestration and tumor progression. This work represents a completely novel process and an exciting potential avenue for therapeutic intervention in the future. Most notably, the publications arising as a result of his doctoral thesis (Journal of Clinical Investigation – August 2013) have been widely reported in the global lay media including National Public Radio, Australian Broadcasting Corporation, and Radio Canada. In addition, this research was cited as one of the top 10 discoveries of 2014 by Quebec Science magazine.

Research Summary:

The majority of patients with cancer undergo at least one surgical procedure as part of their treatment. Severe postsurgical infection is associated with adverse oncologic outcomes; however, the mechanisms underlying this phenomenon are unclear. Emerging evidence suggests that neutrophils, which function as the first line of defense during infections, facilitate cancer progression. Neutrophil extracellular traps (NETs) are extracellular neutrophil-derived DNA webs released in response to inflammatory cues that trap and kill invading pathogens. The role of NETs in cancer progression is entirely unknown. We report that circulating tumor cells become trapped within NETs in vitro under static and dynamic conditions. In a murine model of infection using cecal ligation and puncture, we demonstrated microvascular NET deposition and consequent trapping of circulating lung carcinoma cells within DNA webs. NET trapping was associated with increased formation of hepatic micrometastases at 48 hours and gross metastatic disease burden at 2 weeks following tumor cell injection. These effects were abrogated by NET inhibition with DNAse or a neutrophil elastase inhibitor. These findings implicate NETs in the process of cancer metastasis in the context of systemic infection and identify NETs as potential therapeutic targets.