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1	Prof Fionula Brennan Strategies to identify novel targets for therapeutic intervention in chronic inflammatory disease
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3	Inflammatory synovial joint tissue from RA patients: a source of cells for experimental analysis
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5	RA synovial joint cell ex vivo culture
6	Good evidence that TNF is an important component in the pathology of RA
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9	Anti-TNF Biologicals : circa 2007 Over 1,000,000 patients treated since licensed. Very effect on inflammation and joint protection Market heading towards $10B however…………………………………….. 60-70% response rate Not a Cure Very Costly to make and buy Has to be injected Infectious Risks
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11	In RA synovial joint cell tissue what drives inflammation?
12	Cytokine-activated PBLs are surrogates for RA synovial T cell effector function
13	What is phenotype of Tck effector cell?
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15	Identification of ligand on Tck cells responsible for effector function
16	Microarray analysis
17	Microarray analysis
18	Tck membrane proteins identified by MS/MS (confirmed by FACS)
19	CD38^high population correlated with the CD4CD45RO Tck effector function
20	CD38 Type II transmembrane glycoprotein ectoenzyme catalyses synthesis of cyclic ADP ribose Express on early T and B cells, activated T cells, GC B cells and plasma cells Ligand CD31, expresses on monocytes, granulocytes, platelets, B cells and endothelial cells Induce cell proliferation, inflammatory cytokine production, activation, cell interaction CD38+ plasma cells found in synovial tissues and distinguishes RA from non-RA (Haringman et al, 1999, Rheumatology 38:1074-1080) huMaxCD38 pre-clinical trials (multiple myeloma) http://www.medicalnewstoday.com/medicalnews.php?newsid=44965
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33	"Viral & Non-Viral delivery systems" Viral & Non-Viral delivery systems
34	Applications in RA
35	Delivery Strategies
36	siRNA knockdown of Stat3 in Human Monocytes + Macrophages
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41	Summary TNF validated target in RA Selective abrogation of TNF synthesis at inflammatory sites desirable Opportunity to identify new therapeutic targets using RNAi knock down in models of chronic inflammation