Aleixo Muise

Research Synopsis

Dr. Muise’s clinical work and laboratory research is focused on understanding the genetic susceptibility and function of identified genes in pathogenesis of Very Early Onset Inflammatory Bowel disease (VEOIBD; diagnosed prior to 6 years of age and infantile disease). This has led to a number of publications from his laboratory describing novel genetic and functional studies in IBD (E-cadherin, RAC1, and PTPRS) and VEOIBD. Most importantly, this genetic analysis has led to curative treatments in a number of Canadian and international VEOIBD patients with IL10R mutations. Furthermore, his work has described a novel form of VEOIBD with severe apoptotic entero-colitis and identified the causative mutations – termed TTC7A-deficiency. His lab has shown that mutations in the TTC7A gene result in the severe phenotype through disruption of PI4K signaling and that the PI4K-TTC7A-EFR3B pathway are critical in development of this disease. They have also identified VEOIBD rare functional variants in the NADPH oxidase genes, iNOS, and IL10R that lead to risk of developing VEOIBD and a hope to identify novel treatment strategies based on these genetic findings.

In order to further these studies, Dr. Muise has created the largest repositories of DNA from well phenotyped VEOIBD patients by establishing (a) a clinic at SickKids to ascertain, treat, and follow infants and young children with VEOIBD, and (b) founding the SickKids-based interNational Early Onset Paediatric IBD Cohort Study (NEOPICS; www.NEOPICS.org) consortium. His Canadian and International collaborations with leaders in IBD genetics and immunology have led to a greater understanding of the genetic factors associated with VEOIBD and changed the treatment of these young patients.