Dr. Gregory Downey

Biographical Sketch

Dr. Downey received his B.Sc. (Med) and M.D. from the Faculty of Medicine at the University of Manitoba. He completed training in General Internal Medicine at the Beth Israel and Brigham and Women's Hospital, Harvard University in Boston, MA. He then undertook subspeciality training in Pulmonary and Critical Care Medicine at the University of Colorado affiliated hospitals, followed by research training in pulmonary immunology at National Jewish Medical and Research Center in Denver, CO in the laboratory of Peter Henson. Dr. Downey is currently Director of the Division of Respirology, and Professor and Vice Chair of the Department of Medicine, University of Toronto, a senior scientist in the Toronto General Hospital Research Institute of the University Health Network and the recipient of a Tier 1 Canada Research Chair in Respiration Sciences.

University Appointments

Director, Division of Respirology, The University of Toronto, Professor and Vice-Chair, Department of Medicine, University of Toronto

Hospital Appointments

Staff Physician, Division of Respirology, University Health Network and Mount Sinai Hospital.
Physician, Multi-Organ Transplant Unit, Toronto General Hospital.
Associate Staff, Division of Respiratory Medicine, Hospital for Sick Children.

Clinical Activities

General Respiratory Medicine
Lung Transplantation
Pulmonary Fibrosis
Rare Lung Diseases (lymphangioleiomyomatosis, pulmonary alveolar proteinosis)
Pulmonary Immunology
Pulmonary Vasculitis

Educational Activities

Associate Director, Institute of Medical Sciences, University of Toronto

Current Local, Provincial, National and International Activities

Member of the CIHR Institute of Circulatory and Respiratory Health Advisory Board
Chair, CIHR Investigators committee
Member, Planning Committee, Assembly on Allergy, Immunology, and Inflammation, American Thoracic Society
Chair, Assembly on Allergy, Immunology, and Inflammation International Committee, American Thoracic Society
Associate Editor, American Journal of Respiratory Cell and Molecular Biology
Member of the Rare Lung Diseases Consortium, National Institutes of Health

Research Interests

Mechanisms of inflammatory injury to the lung
Leukocyte activation in sepsis and lung injury
Cell signaling in innate immunity
Focal Adhesion Regulation of Cell Signaling
Regenerative Medicine
The innate immune system in Cystic Fibrosis

Current Grant Support

Agency: National Sanatorium Association
Date and Duration: 06/01-06/06
Title: Program in Pulmonary Fibrosis
PI: Downey, G.
Amount: $1,000,000

Agency: Canada Research Chair, Tier 1 Date and Duration 01/2001-12/2007
Title: Acute Lung Injury and Inflammation
PI: Downey G.
Amount: $200,000 per annum ($1,400,000 total).

Agency: Canada Foundation for Innovation
Date and Duration: 01/2001-12/2007
Title: Acute Lung Injury and Inflammation
PI: Downey G.
Amount: $330,000 total equipment award.

Agency: Canadian Institutes of Health Research Grant #MT-12255
Date and Duration: 10/05-9/10
Title: Tyrosine Phosphatase Regulation of Leukocyte Activation. Implications for Lung Injury
PI: Downey G.
Amount: $129,993 per annum ($649,965 total).

Agency: Canadian Institutes of Health Research Group Grant
Date and Duration: 10/03-10/08
Title: Cellular and Molecular Mechanisms of Organ Injury
PI: Levy G. Co-PIs Downey G, Marsden P, Rotstein O, Cybulsky M, Zhang L.
Amount: $226,259 per annum ($1,131,295 total).

Agency: Canadian Institutes of Health Research Grant # MT-10994
Date and Duration: 4/2004-3/2009
Title: Inflammatory Injury to the Lung Epithelium; Implications for Acute Lung Injury
PI: Downey G.
Amount: $122,295 per annum ($511,475 total)

Agency: Canadian Institutes of Health Research Grant# MOP13187
Date and Duration: 3/2001-3/2006
Title: Signaling of IL-1 through focal adhesions
PI: McCulloch, C Role Co-PI with Dr. C. McCulloch
Amount: $117,000 per annum ($585,305 total)

Agency: Canadian Foundation for Innovation
PI: Arthur Slutsky Role Project Leader
Date and Duration: 7/2001-6/2006
Title: Center for Critical Care Research Excellence
Amount: $5,000,000.

Agency: Canadian Institutes of Health Research Training Grant
Date and Duration: 4/2002-3/2006
Title: Regenerative Medicine
PI: Levy, G. Role Co-PI with Dr. G. Levy
Amount: $225,000 per annum ($675,000 total)

Agency: Canadian Cystic Fibrosis Foundation
Date and Duration: 4/06-4/09
Title: Defective Clearance of Apoptotic Neutrophils from the Lung in Cystic Fibrosis
PI: Downey, G Role Co-PI with Dr. S. Grinstein
Amount: $96,866 per annum ($278,598 total)

Agency: Canadian Foundation for Innovation
PI: Gary Levy Role Project Leader
Date and Duration: 7/2004-6/2009
Title: Center for Research in Immune Tolerance
Amount: $12,000,000.

Agency: National Institutes of Health grant #HL-04-001
PI: Slutsky, AS. Co-PIs: Dorian P and Morrison L.
Role: Scientific Consultant
Date and Duration: 7/2004-6/2009
Title: From Bench to Bedside to Curbside. University of Toronto regional clinical center application to: Clinical research consortium to improve resuscitation outcomes.
Amount: $2,454,201 US over 5 years.

Selected Recent Publications

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Chapters and Monographs

Book Chapters and Reviews 2001-2007.

Chow C-W, and GP. Downey. The Battlefield: Cells and Mediators. In Sepsis and Organ Dysfunction; From Chaos to rationale. Baue AE, Berlot G, Guilo A, and Vincent J-L (Eds). Springer-Verlag Italy. pp 67-76, 2002. SRA

Chow CW, Downey GP, Grinstein S. Phacocytosis. Current Protocols in Cell Biology. Publisher: John Wiley and Sons Inc. Supplement 22. 15.17.7-15.17.31. 2004.

Moraes T, Suzuki T, Downey GP. The Neutrophil; Balancing Antimicrobial Effectiveness and the Potential for Damage to the Host. In 'Textbook of Critical Care, 5th Edition. Fink, Abraham, Kochanek, and Vincent Editors. Elsevier Saunders, Philadelphia PA. pp 133-139, 2005. SRA

Chow CW, Downey GP. Inflammation. Clinical Critical Care Medicine. Editors. Albert, Slutsky, Ranieri, Takala, Torres. Chapter 1, pages 1-12.2005. Publisher: Elsevier, Philadelphia, PA.

Moraes T, Downey GP. Non Immune Host Defenses of the Lung. In: Respiratory Infections - Edited by Torres, Ewig, Mandell & Woodhead. In press, 2005.

oraes TJ, Zurawska J, and Downey GP. Neutrophil Granule Contents in The Pathogenesis Of Lung Injury. Current Opinion In Hematology. 13:21-27, 2006.

Herridge M, Downey GP, Darling G. Bacterial Infections of the Lung. In: Textbook of Thoracic Surgery. Third Edition Ed. Ginzberg R. 2006. Co-Author.

Research Laboratory

The focus of research in my laboratory is on transmembrane signaling events regulating leukocyte activation. The relevance of this is to diseases characterized by inflammatory injury to the lung including acute lung injury and ARDS, cystic fibrosis, and asthma. State of the art techniques in cell and molecular biology including single cell microfluoresence imaging, microinjection, molecular cloning and DNA sequencing, reverse transcriptase PCR, fusion protein expression and mammalian cell transfection with dominant negative proteins, and the generation and study of knockout mice are currently in use in our laboratory. Specific projects currently ongoing include:

1. Genomic and functional characterization of tyrosine and lipid phosphatases expressed in leukocytes. We are focusing on the study of these key signaling molecules including SHP-1, SHP-2, MEG-2, SHIP-1, and PTEN.
2. Interaction of neutrophils with lung epithelial cells related to mechanisms of epithelial dysfunction in lung injury.
3. Determination of the role of tyrosine phosphatases in focal adhesion-dependent signaling in fibroblasts
.
4. Mechanisms of clearance of apoptotic cells in inflammation