Jack Gauldie

, PhD, FRSC, DSc

Distinguished University Professor
Pathology and Molecular Medicine

Division: Molecular Medicine

John Bienenstock Chair in Molecular Medicine
Director, Institute for Molecular Medicine and Health
Member of the Ontario Research Fund (ORF) Advisory Board

McMaster University
4010 Michael DeGroote Centre for Learning & Discovery
905-525-9140 ext 22696
gauldie@mcmaster.ca

Not accepting students at this time

Education and Professional Standing

FRSC, 1997
PhD, University College London (UK), 1968
BSc, McMaster University, 1964

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Interests

Research Focus

Chronic inflammation and tissue remodeling

For a number of years our group has been interested in the molecular events that control the complex process of chronic inflammation. Acute events resulting in the initiation of the inflammatory response are in the most protective and lead to normal tissue repair and return to normal function. We have been studying the molecular controls that govern the conversion of acute responses to chronic inflammatory responses. The chronic nature of the response results in on-going repair and tissue remodeling, with altered cell and matrix deposition and compromise to tissue function. Such is the case in fibrosis, with common mechanisms and mediators in pulmonary, hepatic and dermal fibrosis, as well as joint remodeling.

We use gene transfer technologies to determine the role(s) of individual cytokine genes to the process of fibrogenesis and have shown that over-expression of active TGF 1 in a tissue- or organ-restricted manner leads to chronic fibrogenesis that involves, but is restricted to, the entire organ of expression. TGF 1 delivered to the lung induces progressive pulmonary fibrosis and represents an ideal model of this disease for therapeutic drug discovery. We also use drug- (bleomycin) and radiation-induced models to test the concepts of gene therapy in fibrosis using genes encoding natural inhibitors of TGF. Using a similar approach we are investigating the involvement of fibrogenesis in peritoneal dialysis membrane failure and uses of gene therapy for intervention.

Cytokine gene transfer and models of inflammation will be developed to identify new targets for therapeutic drug discovery through gene array assessments.

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Team Members

Lab Techicians: Xueya Feng, Jane Ann Smith

Selected Publications

• Bonniaud, P., Margetts, P.J., Kolb, M., Haberberger, T., Kelly, M., Robertson, J. and Gauldie,J. Adenoviral gene transfer of connective tissue growth factor in the lung induces transient fibrosis. Am. J. Respir. Crit. Care Med. 168:770-778, 2003.
• Gauldie, J. Letter to Editor: Role of inflammation in idiopathic pulmonary fibrosis: the steroid argument. Am. J. Respir. Crit. Care Med., 2003.
• Gauldie, J., Galt, T., Bonniaud, P., Robbins, C., Kelly, M. and Warburton, D. Transfer of the active form of transforming growth factor-b1 gene to newborn rat lung induces changes consistent with bronchopulmonary dysplasia. Am. J. Pathol. 163:2575-2584, 2003.
• Bonniaud, P., Martin, G., Margetts, P.J., Ask, K., Robertson, J., Gauldie, J. and Kolb, M. Connective tissue growth factor is crucial to inducing a profibrotic environment in “fibrosis-resistant” Balb/C mouse lungs. Am. J. Respir. Cell Mol. Biol. 31:510-516, 2004.
• Bonniaud, P., Kolb, M., Galt, T., Robertson, J., Robbins, C., Stämpfli, M., Lavery, C., Roberts, A.B., Margetts, P.J., Roberts, A.B. and Gauldie, J. Smad3 null mice develop airspace enlargement and are resistant to TGF-b mediated pulmonary fibrosis. J. Immunol. 173:2099-2108, 2004.
• Rodriguez-Lecompte, J.C., Kruth, S., Gyorffy, S., Wan, Y.H. and Gauldie, J. Cell-based cancer gene therapy: breaking tolerance or inducing autoimmunity? Anim. Health Res Rev. 5:227-234, 2004.
• Bonniaud, P., Margetts, P.J., Kolb, M., Schroeder, J.A., Kapoun, A.M., Damm, D., Murphy,A., Chakravarty, S., Dugar, S., Higgins, L., Protter, A.A. and Gauldie, J. Progressive transforming growth factor β1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am. J. Respir. Crit. Care Med. 171:889-898, 2005.
• Vallance, B.A., Gunawan, M.I., Hewlett, B., Bercik, P., Van Kampen, C., Galeazzi, F., Sime,P.J., Gauldie, J. and Collins, S.M. TGF-b1 gene transfer to the mouse colon leads to intestinal fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 289:G116-G128, 2005.
• Chua, F., Gauldie, J. and Laurent, G.J. Pulmonary fibrosis: Searching for model answers.  Am. J. Respir. Cell Mol. Biol. 33:9-13, 2005.
• Bonniaud, P., Margetts, P.J., Ask, K., Flanders, K., Gauldie, J. and Kolb, M. TGF-β and Smad3 signaling link inflammation to chronic fibrogenesis. J. Immunol. 175:5390-5395, 2005.
• Kelly, M.M., Leigh, R., Gilpin, S.E., Cheng, E., Martin, G.E., Radford, K., Cox, G. and Gauldie, J. Cell-specific gene expression in patients with usual interstitial pneumonia. Am. J. Respir. Crit. Care Med. 174:557-565, 2006.
• Gauldie, J., Kolb, M., Ask, K., Martin, G., Bonniaud, P. and Warburton, D.  Smad3 signaling involved in pulmonary fibrosis and emphysema.  Proc. Am. Thorac. Soc. 3:696-702, 2006.
• Kolb, M., Martin, G., Medina M., Ask, K. and Gauldie, J. Gene therapy for pulmonary disease. Chest 130:879-884, 2006.
• Robertson, J.V., Nathu, Z., Najjar, A., Dwivedi, D., Gauldie, J. and West-Mays, J.A. Adenoviral gene transfer of bioactive TGFβ1 to the rodent eye as a novel model for anterior subcapsular cataract. Mol. Vis. 13:457-469, 2007.
• Takenaka, S., Safroneeva, E., Xing, Z. and Gauldie, J.  Dendritic cells derived from murine colonic mucosa have unique functional and phenotypic characteristics. J. Immunol. 15:7984-7993, 2007.
• Gauldie, J., Martin, G.E.M., Ask, K., Gilpin, S. and Kolb, M. The transforming growth factor-beta (TFF) family and pulmonary fibrosis. Drug Discovery Today: Disease Mechanisms. (in press), 2007.
• Moeller, A., Ask, K., Gauldie, J., Warburton, D. and Kolb, M.  The bleomycin model: a useful tool to investigate therapies for idiopathic pulmonary fibrosis? Int. J. Biochem. Cell Biol. (in press), 2007.
• Décologne, N., Kolb, M., Margetts, P.J., Ménétrier, F., Artur, Y., Garrido, C., Gauldie, J., Camus, P. and Bonniaud, P. Transforming growth factor-β1 induces progressive pleural scarring and subpleural fibrosis. J. Immunol. 179:6043-6051, 2007.