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:
MEMBERS OF THE LEASK LAB
Andrew Leask, PhD
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, Ophthalmology & Pathology, Western University
Wei Sha, Assistant Professor, Chaoyang Hospital, Beijing
Chris Elliott, MD Student, University of Ottawa
Shangxi Liu, PhD, Research Scientist back to top
Liu S, Thompson K, Leask A. CCN2 expression by fibroblasts is not required for cutaneous tissue repair. Wound Repair Regen. 2014 Jan;22(1):119-24.
Liu S, Herault Y, Pavlovic G, Leask A. Skin progenitor cells contribute to bleomycin-induced skin fibrosis. Arthritis Rheum. 2013 Nov 18. doi: 10.1002/art.38276
Liu S, Leask A. CCN2 modulates hair follicle cycling in mice. Mol Biol Cell. 2013 Dec;24(24):3939-44.
Liu S, Parapuram SK, Leask A. Fibrosis caused by loss of PTEN expression in mouse fibroblasts is crucially dependent on CCN2. Arthritis Rheum. 2013 Nov;65(11):2940-4.
Bedore J, Sha W, McCann MR, Liu S, Leask A, Séguin CA. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2. Arthritis Rheum. 2013 Oct;65(10):2634-44
Guo F, Hutchenreuther J, Carter DE, Leask A. TAK1 is required for dermal wound healing and homeostasis. J Invest Dermatol. 2013 Jun;133(6):1646-54.
Liu S, Leask A. Integrin β1 is required for dermal homeostasis. J Invest Dermatol. 2013 Apr;133(4):899-906.
Shi-wen X, Thompson K, Khan K, Liu S, Murphy-Marshman H, Baron M, Denton CP, Leask A, Abraham DJ. Focal adhesion kinase and reactive oxygen species contribute to the persistent fibrotic phenotype of lesional scleroderma fibroblasts. Rheumatology (Oxford). 2012 Dec;51(12):2146-54.
Lagares D, Busnadiego O, García-Fernández RA, Kapoor M, Liu S, Carter DE, Abraham D, Shi-Wen X, Carreira P, Fontaine BA, Shea BS, Tager AM, Leask A, Lamas S, Rodríguez-Pascual F. Inhibition of focal adhesion kinase prevents experimental lung fibrosis and myofibroblast formation. Arthritis Rheum. 2012 May;64(5):1653
Elliott CG, Wang J, Guo X, Xu SW, Eastwood M, Guan J, Leask A, Conway SJ, Hamilton DW. Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair. J Cell Sci. 2012 Jan 1;125(Pt 1):121-32
Parapuram SK, Huh K, Liu S, Leask A. Integrin β1 is necessary for the maintenance of corneal structural integrity. Invest Ophthalmol Vis Sci. 2011 Oct 3;52(11):7799-806
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.
The following agencies support ongoing research in this lab:
2015 Summer Research Student Program
Congratulations to David Freere (DDS 2018) who was awarded a Summer Research Studentship to work in Dr. Leask's Lab. Project: The effect of NADPH oxidase inhibitor CPI on CCN family expression in gingival fibroblasts'
Dr. Leask awarded CIHR Operating Grant
Congratulations to Dr. Leask on his 2014 CIHR Operating Grant, funded for 5 years at $156,940 per year, for a total of $784,700. Project: 'CCN2 Action in Fibrosis: Cellular and Molecular Mechanisms’
2014 Summer Research Student Program
Congratulations to Kimberly Williams (DDS 2017) who was awarded a Summer Research Studentship to work in Dr. Leask's Lab. Project: 'Regulation of CCN2 by antioxidants in gingival fibroblasts'
Dr. Leask awarded EULAR Abstract Award
June 2013 - Dr. Andrew Leask, was honoured with one of six European League Against Rheumatism (EULAR) Abstract Awards in Basic Science at a recent meeting in Madrid, Spain. This phenomenal accomplishment highlights the importance of Dr. Leask’s research focused on fibrotic diseases that is caused by excessive and persistent formation of scar tissue. It affects those people living with a variety of different chronic diseases such as liver cirrhosis, diabetes, heart disease, lung fibrosis and scleroderma. There are no therapies on the market today that have been shown to stop or prevent fibrotic disease, which can result in organ failure and death for sufferers.
“Collectively 45 per cent of the deaths and health care costs in developed countries are caused by such diseases, and there is no cure. We want to understand how these diseases occur in the first place,” stated Dr. Leask. “We do know that fibrosis is caused by the excessive production and remodeling of connective tissue by a certain cell type called a myofibroblast. The question we are asking is where did the myofibroblasts come from and how can we stop them from acting?”
Dr. Leask’s abstract, entitled “A Novel Model of Systemic Sclerosis?: Loss of PTEN in Fibroblasts Results in Lung Fibrosis in a CCN2/CTGF-Dependent Fashion”, focused on the lack of a tumor suppressor called PTEN, which the loss of is sufficient to generate myofibroblasts and fibrosis in mice.
“We also have uncovered a potential mechanism of how the loss of PTEN causes fibrosis, which appears to also work on other models of fibrosis as well,” explained Dr. Leask. “Thus we think that targeting this mechanism might result in a therapy for fibrosis”.
The EULAR Congress, which hosted more than 14,000 people offered a wide range of topics including clinical innovations, clinical translational and basic science. Meetings were organized by people with arthritis, health professionals, and the health care industry.
Now a major event in the calendar of world rheumatology, the annual EULAR congress is a significantly recognized platform to facilitate interactions between patients, medical doctors, scientists, health professionals and professionals representing the pharmaceutical industry.
Dr. Leask awarded CIHR Operating Grant
Congratulations to Dr. Leask on his 2012 CIHR Operating Grant of $273,429 (3 years)
Project: "TAK1: A novel fibrogenic mediator?"
Please direct research position and other inquiries to:
Dr. Andrew Leask firstname.lastname@example.org
Schulich Dentistry / Physiology & Pharmacology
Schulich School of Medicine & Dentistry
Western University, London, Ontario, CANADA N6A 5C1
Phone 519.661.2111 x81102 | Fax 519.850-2459