ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
effects on cell proliferation, MMP2/9 production and tubule formation. Furthermore Wei has demonstrated
that VEGF +Ang2 synergistically induces NOTCH 1IC, 3IC and 4IC signalling pathways. Currently we are
using an RA human synovial /SCID mouse model (in collaboration with Prof. Costantino Pitzalis, London) to
examine the effect of blocking either the NOTCH signalling pathway or the Tie-2 receptor on blood vessel
regression Wei was awarded Seed funding through the UCD scheme to travel to the American College of
Rheumatology Boston to present his work.
Fig 3: (above) Dual immunoflourescent staining with
Factor VIII (red) and ·SMA (GREEN). Blood vessel
staining red are immature and those staining for red and
green are mature. This figure shows there is a mixture
of immature and mature vessels in the joint.
(iv) GMCSF and TLRs
Dr. Sinead Nic An Ultaigh has been examining the role of Granulocyte-Macrophage Colony Stimulating
Factor (GM-CSF) as part of our continuing work on cytokine networks in inflammatory arthritis. GM-CSF is
found at higher levels locally in the joints of patients with inflammatory arthritis, while levels in serum were
practically undetectable. Anti-GM-CSF may inhibit pro-inflammatory cytokines in our ex-vivo explant model
from patients with inflammatory arthritis. Preliminary data also indicates that GM-CSF receptor alpha is
expressed in the lining layer of the synovial tissue and in the endothelial cells of blood vessels of arthritis
patients. Sinead is also examining the role of Toll-Like Receptors (TLRs) in inflammatory arthritis. TLRs have
been implicated in autoimmune diseases, and TLR expression has been found in joint tissue and at the sites
of invasion into cartilage/bone of patients with RA and PsA. Sinead has shown that cytokines and
chemokines are increased in PBMCs, primary fibroblasts and novel ex-vivo synovial explants from patients
with inflammatory arthritis when stimulated with TLR 2 and 4 agonists. Prelimiary data has also
demonstrated induction of NOTCH 1 in synovial fibroblasts in response to TLR-2 and TL-4 stimulation.
Future work will focus on the interaction of Notch and NFκB in response to TLR signalling.
(v) Proof of Concept Studies
Jennifer Mc Cormick is an integral part of the team and is involved in a number of projects in the group. In
particular Jenny works on the signalling pathways and matrix invasion using zymography with Mary, Aisling
and Ellen. She processes the tissue, cells, serums/ synovial fluids from all of the arthroscopies which are
vital to all of the research carried out in the group. We have developed a number of partnerships with the
drug discovery and translational teams within industry led by Prof Veale. Jenny, Ursula and Sinead carry out
these studies using synovial explant cultures, MSD multiplex assays and transcriptomics to establish preclinical
and ‘proof of concept’ drug development studies of novel bio therapeutics and small molecular weight
candidates.
(2) Remission study and Rituximab therapy for resistant arthritis
Withdrawal of anti-TNFα therapy in patients with rheumatoid arthritis in clinical remission: can maintenance
of remission be predicted? The primary goal of this trial is to determine if clinical remission can be maintained
Return to Contents
26