KD is a multi-system vasculitis affecting children. The vessels most commonly damaged are the coronary arteries, making KD the number one cause of acquired heart disease in children from the industrialized world.  I use KD as an experimental model for studying autoimmunity and have applied our findings to study childhood arthritis. Exposure to an environmental agent in a genetically susceptible host is common to systemic autoimmune diseases, making KD a prototypic disease model. I study the molecular and cellular mechanisms responsible for inflammation and vessel breakdown and am also actively involved in clinical care of affected children. I care for the largest cohort of multi-ethnic children with KD in the world, I have built a multi-disciplinary nation-wide team in KD research and linked Canada with the International KD Genetics Consortium, on which I serve as chair of the scientific committee. My goals are to define the genetic, molecular and cellular interactions, which dictate immune dysfunction in KD, and therefore gain new understanding of disease pathogenesis, identify biomarkers for aneurysm formation, improve management and disease outcome. Our current research encompasses multiple facets accounting for factors stemming from various levels: genetic blueprint, gene and protein expression, biologic function, immune response to novel environment danger signals and impact on disease, outcome and quality of life for the affected child and family.

Childhood arthritis is not one disease but a group of rare and heterogeneous diseases. Despite advances in understanding the immunobiology of arthritis, few have proved useful for predicting response to treatment in childhood arthritis. Recent work by my team has established that patients and treatment response can be meaningfully classified using approaches that integrate comprehensive proteomic, transcriptomic and clinical data. No single individual or centre can tackle the complex interactions of genetics, environment and lifestyle on the risks and outcomes of rare diseases such as KD and childhood arthritis. Collaboration is the key to resolving biology and improving outcome in these rare diseases. To foster research, improve efficiencies and combine resources to study rare diseases, I helped develop a national research network (CAPRI-Canadian Alliance of Paediatric Rheumatology Investigators), and served as the inaugural chair, helping to lead four Canada-wide, multi-disciplinary group grants to study childhood arthritis, continuing my thematic studies on immune activation in childhood autoimmunity. We have developed a robust national research infra-structure to support translational research including: a standardized data collection system for clinical phenotyping, processing and storage of biologic specimens, communications website, partnership funding for trainee support, and a strong organizational structure to develop guidelines, monitor research and tackle issues related to science, education, publication and knowledge translation and exchange. My laboratory currently houses the national tissue repository. I am honored to have served as the inaugural chair of CAPRI, our national research network, whose mission is to foster research, improve efficiencies and combine resources. Building on the lessons learned from our national network, I have assembled a multi-disciplinary, international translational research network that will extend our ongoing collaborations. Most recently we successfully launched UCAN CAN-DU:  Canada-Netherlands Network in Precision Medicine in Childhood Arthritis and Rheumatic Disease.

We initiated studies on molecular mechanisms starting with children who suffer from rare forms of systemic vasculitis with extreme phenotypes and very early onset disease. Whole exome sequencing (WES) has been carried out on DNA of probands and parent-child trios (and siblings when available) without a family history. In addition, WES was performed on a small number of familial cases with multiply affected family members. By prioritizing patients with rare severe early onset forms of disease we enriched for monogenetic Mendalian forms of disease to provide clues on the molecular pathogenesis of these inflammatory disorders. Massively parallel next-generation DNA sequencing technology is revolutionizing our understanding of disease. This recent work is in collaborations in the context of a CIHR funded team in chronic inflammatory diseases (Brumell – team lead) has partnered pioneering work in very early onset IBD and extended it to systemic vasculitis. Using this model of discovery in those with extreme phenotypes has proven to be extremely successful in children with systemic vasculitis. Novel findings in a single gene has lead not only to actionable treatment in those with extreme phenotypes, but also lead to identification of key biologic pathways in those with more common presentations of similar diseases.