DR. BRENT W. WINSTON

 

MD (University of Alberta), FRCPC, FACP, FCCP, FCCM, Associate Professor, Departments of Medicine and Biochemistry & Molecular Biology.

Affiliations:  Member - Immunology Research Group.

Research Interests:

The research focus in my laboratory has been directed toward macrophage functional differentiation, specifically towards inflammatory gene regulation in macrophages.  For example, when murine bone marrow-derived macrophages are exposed to TNFa, they upregulate a set of genes (IGF-I is one example) and differentiate towards a pathway which may take part in wound repair/fibrosis. However, when these same macrophages are exposed to TNFa in the presence of interferons (IFN's), they differentiate along a pathway which upregulates inflammatory genes like the alternative complement cascade factor B (Bf) or inducible nitric oxide synthase (iNOS). Each of these pathways may have disease related implications.  For example, Bf is an important complement factor in the activation of the alternative complement cascade in sepsis, whereas IGF-I may play an important role in pulmonary fibroproliferation (scar formation in the lungs). Research in my laboratory has remained focused on macrophage functional differentiation, particularly on three main related themes:

1) Insulin-like growth factor-I (IGF-I) gene regulation and induction in fibrotic lung diseases.  We are involved in both human and murine studies to examine the role of IGF-I on pulmonary fibroproliferation.

2) Alternative complement cascade Factor B gene regulation and induction in sepsis.  We are involved in human studies and use murine in vivo models to examine the role of the alternative complement cascade, specifically factor B, in shock and organ dysfunction in sepsis.

3) TNFa signaling: activation of downstream kinases in macrophages.  We are particularly interested in TNFa-mediated MEKK1 activation in macrophages.   My laboratory is well positioned to conducting translational research on clinically relevant Critical Care and Pulmonary disease processes.

Winston Lab

Personnel:

BMB Graduate Student:	Ai Ni, M.Sc.
Graduate Student:	Stacey Bertsch
Technician:	Connie Mowat
Administrative Assistant:	Ms. Leslie Cooper

 

View Pub Med for Recent publications & abstracts

Recent Publications:

Book

Edward D. Chan, John B. Kortbeek, Lance S. Terrata, and Brent W. Winston . Bedside Critical Care Manual.  Second Edition.  Hanley and Belfus, Inc., Philadelphia, PA. 2002.

Journal Papers/Articles

• Yong Huang, Peter M. Krein, and Brent W. Winston.  Characterization of IFNg Regulation of the Complement Factor B Gene in Macrophages. Eur. J. Immunol.,  2001, Vol. 31:3676-3686. This was the last issue of last year.
• Peter M. Krein and Brent W. Winston.  Roles for Insulin-like Growth Factor I (IGF-I) and Transforming Growth Factor-beta (TGF-b) in Fibrotic Lung Disease.  Chest, 2002, Vol. 122(6): 289S-293S.
• Peter M. Krein, Peter Sabatini, William Tinmouth, Francis Green, and Brent Winston.  IGF-I Immunoreactivity is Increased in the Lungs of Patients with Fibroproliferative ARDS.  Am. J.  Resp. Crit. Care Med., 2002, 166(12):
• Yong Huang, Peter M. Krein, Daniel A. Muruve and Brent W. Winston.  Complement Factor B Gene Regulation: Synergistic effects of TNFa and IFNg in macrophages.  J. Immunol., 2002, 169: 2627-2635.
•  Peter M. Krein, Ron Brisebois, Christopher Doig, Francis  Green and Brent W. Winston. IGF-I levels are increased in the lungs of patients with fibroproliferative ARDS.  Manuscript submitted to the American Journal of Respiratory and Critical Care Medicine, (2002)
• Peter M. Krein,Yong Huang and Brent W. Winston. Growth Factor regulation and Manipulation in wound repair:  to scar or not to scar, that is the question. Expert. Opin. Ther. Patents, 2001, Vol. 11(7):1065-1079.
• David Zygun, Ian Anderson, Kevin Laupland, Andreas Kramer, Christopher Doig and Brent W. Winston. Update in Critical Care Medicine in the New Millennium. Annals  RCSPC, 2001, Vol. 34(5): 297-301.
• Yong Huang, Tiliang Deng and Brent W. Winston. Identification and Characterization of a Transcriptional and Splicing Factor Phosphorylation Kinase. Biochem. Biophys. Res. Commun., 2000, 271(2), pp 456-463.
• Connie Mowat, Sebine Bisson, Stephen Robbins and, Brent W. Winston. TNF" stimulates MEKK1 translocation into Lipid Rafts (or low density membrane microdomains, LDMC's) in macrophages. Am. J. Resp. and Crit. Care Med. Vol. 161 (3), 2000, pp A455.
• Yong Huang, Peter M. Krein and Brent W. Winston. Regulation of Complement factor B by IFN( and TNF" in macrophages. Am. J. Resp. and Crit. Care Med. Vol. 161 (3), 2000, pp A535.
• B. W. Winston, W. Tinmouth, G. Gelfand, S. McFadden; R. Brisebois, and F. H. Y. Green. Insulin-like Growth Factor-I (IGF-I) is expressed in human lung tissue in fibroproliferative ARDS. Am. J. Resp. and Crit. Care Med. Vol. 161 (3), 2000, pp A95.

Contact Information:

The University of Calgary,
Room 1843 Health Sciences Centre,
3330 Hospital Drive NW, Calgary, Alberta
Canada T2N 4N1
Phone (403) 220-4331
Fax: (403) 283-1267
E-mail: bwinston [at] ucalgary [dot] ca.