Dr. John Laffey

Lab Description

Dr. Laffey's lab is focused on translational studies of cell and gene based therapies for Acute Respiratory Distress Syndrome (ARDS). They have substantial expertise and experience in relevant pre-clinical models of ARDS and sepsis for translational research. Additional capabilities include live cell imaging, intravital microscopy of intact lung, and flow cytomtery. They are located in the brand new, state-of-the-art Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto. Research Core Facilities includes both common and specialized facilities, such as Flow Cytometry, Molecular Biology, Histology and Bioimaging. The Research Bioimaging Facility has a variety of specialized equipment for image capture, analysis and display that we use regularly including confocal microscopes providing thin optical sections of single cells and an advanced live cell imaging system.  In addition, a state-of-the-art vivarium is available. 

Research Focus

Two areas are under study in Dr. Laffey's laboratory. The first strand is optimizing the therapeutic potential of mesenchymal stromal cells in relevant preclinical models of Acute Respiratory Distress Syndrome and Sepsis. Ongoing studies, in rodent and murine models of Ventilator Induced Lung Injury, LPS injury, E. coli pneumonia, and in cecal ligation and puncture, are determining the optimal MSC source, and dose related issues such as route, timing. Insights from these studies will inform subsequent early phase clinical trials.

The second area examines the mechanisms of action of mesenchymal stromal cells in ARDS and sepsis, in order to enhance the activity of these cells and to develop second generation cell therapies for subsequent preclinical testing. These studies utilize in vitro functional assays (epithelial and endothelial wound repair, monocyte inflammation and polarization status). Ongoing studies examine the fate of MSCs in the pulmonary vasculature using a microfluidics device in vitro and intra-vital sub-pleural imaging in vivo. 

Selected Publications 

1. Devaney J, Horie S, Masterson C, Elliman SJ, Barry F, O’Brien T, Curley GF, O’Toole D, Laffey JG. Human mesenchymal stromal cell therapy decreases the severity of acute lung injury induced by E.coli . ThoraxJul;70(7):625-35. doi: 10.1136/thoraxjnl-2015-206813. [PMID: 25986435].
2. MacLoughlin RJ, Higgins BD, O’Toole D, Laffey JG, O'Brien T. Aerosol-mediated delivery of AAV2/6-IkBa attenuates lipopolysaccharide-induced acute lung injury in rats. Hum Gene TherJan;26(1):36-46 [PMID: 25382145] 
3. Hayes M, Masterson C, Devaney J, Barry F, Elliman SJ, O’Brien T, O’Toole D, Curley G, Laffey JG. Anesthesiology2015 Feb;122(2):363-73. PMID: 25490744.
4. McAuley DF, Laffey JG, O’Kane CM, Perkins GD, Mullan B, Trinder J, Johnston P, Hopkins PA, Johnston AJ, McDowell C, McNally C, and the HARP-2 investigators* on behalf of the Irish Critical Care Trials Group. Simvastatin in Acute Respiratory Distress Syndrome. N Engl J Med. 2014 Oct 30;371(18):1695-703. [PMID: 25268516]
5. Devaney J, Curley GF, Hayes M, Masterson C, Ansari B, O’Brien T, O’Toole D, Laffey JG. Inhibition of pulmonary Nuclear Factor kappa-B decreases the severity of acute E. coli pneumonia but worsens prolonged pneumonia. Critical Care 2013 Apr 27;17(2):R82 

John Laffey

E: laffyej@smh.ca
P: (416) 864-5071
F: (416) 864-6014

http://stmichaelshospitalresearch.ca/research-programs/critical-illness-and-injury-research-centre/

Laboratory Members

Dr. John Laffey: Principal Investigator
Dr. Mirjana Jerkic, MD, PhD: Research Associate
Dr. Claire Masterson: Post-doctoral Fellow
Stéphane Gagnon: Research Technician
Grace Hogan: Masters’ Student
Dr Kate Tatham: Critical Care Fellow
Dr. Allen Volchuk, PhD: Research Associate