Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by arthritis affecting predominantly the joints of the spine. It is the most common arthritis of the spine and affects 1% of the Canadian population. Uncontrolled inflammation can lead to osteoproliferation, with pathologic new bone formation and eventually bony ankylosis of the spine. The cause of AS is unknown and the basic mechanisms underlying chronic inflammation remains undefined. With the advent of genome-wide association studies (GWAS), several new genes have been identified and this could potentially open up information of novel pathways and drug targets in AS.
- Clinical ResearchThe clinical arm of my research program includes identification of biomarkers and prediction models of severe disease. We recently reported a 70% reduced risk of progression of AS if we start treating these patients early with a class of medicines that target Tumor Necrosis Factor α. This was the first report to suggest that damage in AS can be prevented with appropriate therapy. Currently we are working on identifying patients with spondyloarthritis even before the x-rays become abnormal. We are using MRI techniques and gene expression profiles to develop a prediction model.
- Translational and Basic Science ResearchMy laboratory research program involves identifying novel pathogenic pathways in AS. We are currently exploring the role of a new gene 'ERAP1' that was found to be strongly associated with AS in GWAS studies. ERAP1 is an aminopeptidase that clips peptides to be presented on Major Histocompatibility Complex Class-I molecules like HLA-B27. HLA-B27 is present in 90% of AS patients and the ERAP1 association is seen only in HLA-B27 positive patients. Thus there is likely a functional interaction between these two genes that may be pathogenic in AS. We were the first group to report on the receptor shedding function of ERAP1 in AS patients. Subsequently we showed for the first time that AS associated ERAP1 variants cause changes in HLA-B27 expression on monocytes of AS patients. We are looking at the impact of this genetic interaction on several cellular pathways and trying to identify novel targets for the treatment of AS.
Arthritis Rheumatol. 2019 Jan 07;:
Evolving concepts of new bone formation in axial spondyloarthritis: Insights from animal models and human studies.
Best Pract Res Clin Rheumatol. 2017 12;31(6):877-886
Curr Rheumatol Rep. 2018 Nov 08;20(12):82
Ann Rheum Dis. 2018 Oct 04;:
Pro-inflammatory CX3CR1+ CD59+ TL1A+ IL-23+ monocytes are expanded in patients with Ankylosing Spondylitis and modulate ILC3 immune functions.
Arthritis Rheumatol. 2018 Jun 05;:
Nat Rev Rheumatol. 2018 May 11;:
Simultaneous inhibition of α4/β7 integrin and tumour necrosis factor-α in concomitant spondyloarthritis and inflammatory bowel disease.
Ann Rheum Dis. 2017 Dec 29;:
Arthritis Care Res (Hoboken). 2017 Nov 10;:
Rheumatology (Oxford). 2017 Oct 01;56(10):1740-1745
Arthritis Care Res (Hoboken). 2017 Jul 21;:
Scientist, Krembil Research Institute (Krembil)
Clinician Scientist, University Health Network
Assistant Professor of Medicine and Rheumatology, University of Toronto
Chair, Wait Time Alliance Initiative, Canadian Rheumatology Association
Member, Research Ethics Board, University Health Network
Faculty, School of Graduate Studies, Institute of Medical Sciences, University of Toronto
Graduate Faculty Member, Toronto Musculoskeletal Center, University of Toronto