Leask Laboratory
Fibroproliferative Disease Research
 

Ongoing Research
Members of the Leask Lab
Alumni
Publications
Research Funding
News
Contact Information
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ONGOING RESEARCH

Fibrotic Diseases

We are using a combination of transgenic and gene knockout approaches to uncover the processes involved in progressive fibrotic disease. Although the individual diseases may be rare, there is no effective therapy. Collectively they present a significant health care burden. Genetic manipulation of the central cell type that involved in connective tissue deposition, the fibroblast, is a prerequisite to developing targeted therapeutic modalities for fibrotic diseases.  In particular, we work on the growth factors and signaling cascades resulting in fibrogenesis with an aim in identifying specific target points for drug intervention in fibrotic disease, using scleroderma as a model. Currently, we are interested in the regulation and function of connective tissue growth factor (CTGF, CCN2) in normal and fibrotic cells.  In addition, we are interested in understanding the interplay among TGFbeta, endothelin-1 and CTGF and how pro-fibrotic pathways downstream of these proteins might be selectively blocked, in the expectation that our approach will uncover novel anti-fibrotic therapies.

The Leask Lab collaborates with the following individuals and organizations:

• David Abraham, Carol Black, Richard Stratton, Chris Denton
  University College, London, UK 
• Cheryle Seguin
  The University of Western Ontario 
• Lynne Postovit
  The University of Western Ontario 
• David Brigstock
  Nationwide Children's Hospital (Columbus, Ohio)
• George Bou-Gharios
  Imperial College 
• Thomas Krieg
  University of Cologne
• Murray Baron
  McGill University

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MEMBERS OF THE LEASK LAB


		Dr. Andrew Leask, PhD  Principal Investigator Department of Physiology & Pharmacology Schulich Dentistry Schulich School of Medicine & Dentistry The University of Western Ontario London, Ontario, CANADA N6A 5C1 Phone: 519.661.2111 x81102   Fax: 519.850.2459 Email: andrew.leask@schulich.uwo.ca
		Dr. Shangxi Liu, PhD Research Scientist sliu232@uwo.ca Project:  Adhesive Signaling in Fibrosis
		Fen Guo, Postdoc fguo9@uwo.ca Project: Gingival fibrosis
		Katherine Thompson, Undergraduate kthomp58@uwo.ca Project:  Role of CCN family members in fibrosis
		Jake Bedore, PhD Candidate Project: Role of CCN family members in notochord function
		James Hutchenreuther, MSc Candidate Role of CCN2 in cancers
		Hanna Kuk, MSc Candidate Project: Role of TAK1 in fibroblast function
		Chris Elliott, PhD Candidate Project: Role of periostin in tissue remodelin

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ALUMNI / CURRENT POSITION
 

Mohi Kapoor, Research Assistant Professor, Montreal  

Jason Rockel, Postdoc, University of Toronto

Susan Sa, Senior Research Associate, Genentech

June Chen, Senior Research Associate, Genentech  

Alan Holmes, Project Leader, Novartis 

Xu Shiwen, Senior Lecturer, University College London 

Yunliang Chen, Scientist, Imperial College London

Laura Kennedy, Clinical Trials Ccoordinator, St Joseph's Hospital, London, ON

Sunil Parapuram, Assistant Professor, Depts of Ophthalmology and Pathology, The University of Western

Wei Sha, Assistant Professor, Chaoyang Hospital, Beijing  

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SELECTED PUBLICATIONS 

Trainees are underlined. 

• Guo F, Carter DE, Mukhopadhyay A, Leask A. Gingival fibroblasts display reduced adhesion and spreading on extracellular matrix: a possible basis for scarless tissue repair? PLoS One 2011;6(11):e27097.

• Parapuram SK, Shi-wen X, Elliott C, Welch ID, Jones H, Baron M, Denton CP, Abraham DJ, Leask A.  Loss of PTEN expression by dermal fibroblasts causes skin fibrosis. J Invest Dermatol 2011 Oct;131(10):1996-2003

• Liu S, Shi-wen X, Abraham DJ, Leask A.  2011.  CCN2 is required for bleomycin-induced skin fibrosis in mice.  Arthritis Rheum 63:239-46    

• Thompson K, Hamilton DW, Leask A.  2010.  ALK5 inhibition blocks TGFß-induced CCN2 expression in gingival fibroblasts.  J Dent Res 89:1450-4 

• Liu S, Shi-wen X, Blumbach K, Eastwood M, Eckes B, Denton CP, Krieg T, Abraham DJ, Leask A.  2010.  Expression of integrin beta1 by fibroblasts is required for tissue repair in vivo. J Cell Sci 123, 3674-82   

• Leask A.  2010.  Potential therapeutic targets for cardiac fibrosis: TGFbeta, Angiotensin, endothelin, CCN2 and PDGF, partners in fibroblast activation.  Circ Res 106:1675-80  

• Shi-wen X, Liu S, Eastwood M, Sonnylal S, DentonCP, Abraham DJ, Leask A.  2009. Rac inhibition reverses the phenotype of fibrotic fibroblasts.  PLoS ONE 4(10):e7438

• Kapoor M, McCann M, Liu S, Huh K, DentonCP, Abraham DJ, Leask A. 2009.  Loss of PPARg in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum 60, 2822-2829

• Liu S, Kapoor M, Leask A. 2009.  Rac1 expression by fibroblasts is required for tissue repair in vivo.  Am J Pathol 174:1847-56. Faculty of 1000 must read

• Rockel JS, Bernier SM, Leask A.  2009.  Egr-1 inhibits the expression of extracellular matrix genes in chondrocytes by TNF-alpha-induced MEK/ERK signaling.  Arthritis Res Ther 11, R8

• Leask A, Shi-Wen X, Khan K, Chen Y, Holmes A, Eastwood M, DentonCP, Black CM, Abraham DJ.  2008.  Loss of protein kinase Cepsilon results in impaired cutaneous wound closure and myofibroblast function.  J Cell Sci 121, 3459-67.  Faculty of 1000 must read  

• Kennedy L, Shi-wen X, Carter DE, Abraham DJ, Leask A.  2008.  Fibroblast adhesion results in the induction of a matrix remodeling gene expression program.  Matrix Biol 27:274-81. Faculty of 1000 recommended  

• Pala D, Kapoor M, Woods A, Kennedy L, Liu S, Chen S, Bursell L, Lyons K, Carter D, Beier F, Leask A.  2008.  FAK/src suppresses early chondrogenesis: Central role of CCN2. J Biol Chem 283: 9239-47 

• Liu S, Shi-wen X, Kennedy L, Pala D, Carter DE, Black CM, Abraham DJ, Leask A. 2007. FAK is required for TGFb-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix remodeling phenotype. Mol Biol Cell 18: 2169-2178 

• Shi-wen X, Rodrigues-Pascual F, Lamas S, Holmes A, Howat S, Pearson JD, Dashwood MR, du Bois RM, Denton CP, Black CM, Abraham DJ, Leask A. 2006.  Constitutive ALK5-indepenent JNK activation contributes to endothelin-1 over-expression in pulmonary fibrosis. Mol Cell Biol 26:5518-27. Faculty of 1000 Medicine must read

• Chen Y, Shi-wen X, van Beek J, Kennedy L, McLeod M, Renzoni EA, Bou-Gharios G, Wilcox-Adelman S, Goetinck PF, Eastwood M, Black CM, Abraham DJ, Leask A.  2005. Matrix contraction by dermal fibroblasts requires TGFbeta/ALK5, heparan sulfate containing proteoglycans and MEK/ERK: Insights into pathological scarring in chronic fibrotic disease. Am J Pathol 167: 1699-1711.  Faculty of 1000 Biology recommended

• Chen Y, Abraham DJ, Shi-wen X, Pearson JD, Black CM, LyonsKM, Leask A. 2004. CCN2 (Connective Tissue Growth Factor) Promotes Fibroblast Adhesion to Fibronectin. Mol Biol Cell 15:5635-46   

• Shi-wen X, Chen Y, Denton CP, Eastwood M, Renzoni E, Bou-Gharios G, Dashwood MR, duBois R, Black CM, Leask A, Abraham DJ.  2004. Endothelin-1 promotes mechanoregulation and myofibroblast formation in fibroblasts through the ETA receptor via Akt/PI3 kinase: implications for lung fibrosis. Mol Biol Cell 15:2707-19 

• Leask A, Abraham DJ.  2004.  TGFß signaling and the fibrotic response.  FASEB J 18:816-27   

• Stratton R, Rajkumar V, Ponticos M, Nichols B, Shi-wen X, Black CM, Abraham DJ, Leask A. 2002.  Prostacyclin derivatives prevent the fibrotic response to TGFß2 by inhibiting the ras/MEK/ERK pathway.  FASEB J 16: 1949-51  

• Stratton R, Shiwen X, Martini G, Holme A, Leask A, Haberberger T, Martin GR, Black CM, Abraham D.  2001. Iloprost suppresses connective tissue growth factor production in skin fibroblasts and in the skin of scleroderma patients. J Clin Invest 108: 241-50 

• Holmes A, Abraham DJ, Sa S, Shi-wen X, Black CM, Leask A. 2001. CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling.  J Biol Chem 276: 10594-601. 

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RESEARCH FUNDING

The following agencies support ongoing research in this lab:

• The Scleroderma Society
• The Raynaud's and Scleroderma Association
• The Canadian Institutes of Health Research
• The Arthritis Society
• The Canadian Foundation for Innovation

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NEWS
 

• We are pleased to announce that Mohit Kapoor, a post-doctoral fellow in the Leask lab, was recently awarded the Ontario Ministry of Research & Innovation Postdoctoral Fellowship. The award is a 2-year fellowship to investigate the role of PPAR gamma in wound and tissue repair. Congratulations to Mohit!
  Posted: August 24th, 2007


• Dr. Leask will be presenting at the upcoming Endothelin-1 meeting this coming September 16th-19th in Bergamo, Italy. The presentation will be: "The role of endothelin-1 in mediating adhesive responses".
  Posted: August 23rd, 2007

CONTACT INFORMATION

Please direct research position and other inquiries to:

Dr. Andrew Leask
Department of Physiology & Pharmacology
Schulich School of Medicine & Dentistry
The University of Western Ontario
London, Ontario, CANADA, N6A 5C1
Phone    519.661.2111 x81102
Fax        519.850-2459
Email     andrew.leask@schulich.uwo.ca

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