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PGP 2008-2009 | PGP 2009-2010 | PGP 2010-2011
SRP 2009-2010 | SRP 2010-2011
DAP: 2008 | 2009 | 2010 | 2011
PPG: 2008 | 2009 | 2010
SRI in OA 2003-2008 | SRI in IJD 2006-2011 | SRI in BIO 2008-2012
SRID: 2007-2008 | 2006-2007 | 2005-2006 | 2004-2005 | 2003-2005 | 2002-2004
Research Grants Awards
Research funding: 2003-2005
Genetics
Inflammation
Cellular and molecular biology of joint tissues
Diagnostics & therapeutics
Methodologies & outcomes
Genetics
Analysis of Extracellular Matrix
Molecule Mutations in Individuals
with Ehlers-Danlos Syndromes: A Cause
of Premature Osteoarthritis
Principle Investigator: Dr. W.G. Cole
Co-Principle Investigator: P. Roughley
Abstract
Instability of multiple joints, resulting in chronic joint
pain and premature osteoarthritis, is a major feature of
the Ehlers-Danlos syndrome. The proposed project will complete
current studies of novel mutations of the type V collagen
genes in patients with the types I-III forms of the syndrome.
The gene responsible for a novel form of type III Ehlers-Danlos
syndrome and severe myopia will also be identified. The
disease-gene has been localized to chromosome 17q. Detailed
analyses of the production of the extracellular matrix will
also be completed in all cases in whom mutations have been
identified. These studies also include gene expression studies
using DNA arrays as a means of determining the primary and
secondary events involved in the molecular pathology of
the syndrome.
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Inflammation
Cellular Interactions in the synovium:
Molecular and Functional Analysis
Principle Investigator: Walid
Mourad
Co-Principle Investigators: F. Aoudjit,
H. El-Gabalawy, J. Wilkins
Abstract
Signals for cell growth/survival, and redistribution are
initiated by membrane associated events. 75% of all new
biological therapies currently in clinical developent target
membrane proteins or their ligands.The proposed research
will use proteomics and cell biology for the identification
of new membrane targets for therapeutic intervention in
arthritis.
Regulation of inflammation by perturbation of adhesion
complexes
Principle Investigator: Chris
McCulloch
Co-Principle Investigators: C. Overall,
K. Siminovitch, J. Sodek
Abstract
Arthritic diseases are characterized
by inflammatory degradation of joint
tissues, pain and loss of function.
We have devised a novel approach to
regulation of inflammation in synoviocytes
based on inhibition of IL-1 signaling.
As pro-inflammatory signaling through
IL-1 receptors requires receptor clustering
in adhesion domains, we developed
peptides that inhibit IL-1 signaling
by interfering with receptor aggregation.
The objectives of this proposal are
to: 1) Determine if the novel peptides
block collagenase 1and 3 expression;
2) Identify which key signaling proteins
are blocked from aggregation by the
peptides; 3) On the basis of data
from #1 and #2, optimize the anti-focal
adhesion peptides so that they can
be then tested in animal models of
arthritis.
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Cellular and molecular biology of joint tissues
Promotion of cartilage health and repair by glucosamine
analogues
Principle Investigator: Suzanne
M. Bernier
Co-Principle Investigators: A. Recklies,
T. Anasstasiades
Abstract
Glucosamine is a major component of complementary therapies
used by the public to treat arthritis. These studies investigate
the mechanisms by which a specific glucosamine analogue
augments the ability of cartilage cells to replenish vital
matrix proteins. This process is critical for preventing
cartilage degeneration and improving cartilage regeneration.
Anti-inflammatory chemokine antagonists for treating
arthritis
Principle Investigator:
Chris Overall
Co-Principle Investigators: C. McCulloch,
C. Roberts, J. Schrader
Abstract
To identify novel inhibitors that will effectively block
recruitment and activation of pro-inflammatory immune and
inflammatory cells in articular cartilage and the synovium.
In particular, we will study how the group of pro-inflammatory
mediators termed chemokines are proteolytically inactivated.
Our previous CAN funded work identified that tissue-degrading
enzymes (matrix metalloproteinases; MMPs) also efficiently
cleave chemokines to produce chemokine antagonists. This
heralds a potentially new class of anti-inflammatory agents
for the treatment of arthritis.
Metalloproteases and Cartilage Destruction in Mouse
Models of Arthritis
Principle Investigator:
John S. Mort
Co-Principle Investigator: R. Khokha
Abstract
Cartilage destruction is an irreversible consequence of
arthritis pathology. The major objective of this proposal
is to use genetically modified mice to determine the role
of an endogenous inhibitor of metalloproteases in this process
and to investigate the use of such inhibitors as possible
therapeutic agents.
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Diagnostics & therapeutics
Validation of a rabbit model
of osteoarthritis using non-invasive
imaging echniques
Principle Investigator:
David W. Holdsworth
Co-Principle Investigators: S. Foster,
S. Laverty, C. Webber
Abstract
Osteoarthritis is characterized by focal degeneration of
articular cartilage and changes in underlying subchondral
bone. Evaluation early disease is difficult since, to date,
there has been no technique available to objectively quantify
the disease severity. We propose to apply novel non-invasive
imaging techniques to an animal model of OA, to quantify
disease progression.
Synovial Outcomes in Rheumatoid Arthritis Therapy
Principle Investigator:
Hani El-Gabalawy
Co-Principle Investigators: P. Haraoui,
E. Keystone, J. Wilkins
Abstract
Response to therapy in RA is unpredictable, incomplete,
and the mechanisms not well understood. To address these
challenges, we will undertake studies evaluating the effects
of therapy on RA synovium, blood, and urine, using molecular
pathology, gene expression microarrays, and proteomics.
We hope this will aid in predicting response to current
and future RA therapies, while enhancing the understanding
of how the drugs affect inflamed synovium.
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Methodologies & outcomes
Assessing the quality of care in RA at a population
level
Principle Investigator: Diane
Lacaille
Co-Principle Investigators: M. Abrahamowicz,
A. Anis, J. Esdaile
Abstract not available.
Is access to medication for musculoskeletal diseases
affected by PharmaCare funding in
B.C.?
Principle Investigator: Aslam
Anis
Co-Principle Investigators: J. Esdaile,
D. Lacaille
Abstract
Previous research conducted in the
U.S. has shown that patient co-payment
for prescription drugs leads to a
reduction in overall health resource
utilization. However, in the Canadian
system where health care is provided
free of charge except for drugs, the
converse may be true. Thus, in a disease
such as rheumatoid arthritis that
is primarily managed by increasingly
expensive medications, drug co-payment
may actually be increasing health
expenditures. The objective of this
research is to determine if this hypothesis
is true.
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