Principal investigator:

Aleixo Muise MD, PhD, FRCPC, Co-Director SickKids IBD Centre, Division of Gastroenterology, Hospital for Sick Children, SickKids IBD Centre, University of Toronto

His 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, the genetic analysis has lead to curative treatments in a number of Canadian and international VEOIBD patients with IL10R, XIAP, and LRBA mutations. Furthermore his lab described a novel form of VEOIBD with severe apoptotic entero-colitis and identified the causative mutations – TTC7A-deficiency was termed. 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 is critical in development of this disease. He identified a causative PLVAP mutation resulting in a novel form of sieving Protein Losing Enteropathy (PLE) characterized by hypoproteinemia, hypoalbuminemia, and hypertriglyceridemia. Most recently his group identified ARPC1b as a cause PID and autoimmunity. He has also identified 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, he 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 Pediatric IBD Cohort Study (NEOPICS; www.NEOPICS.org) consortium. His Canadian and International collaborations with leaders in IBD genetics and immunology have lead to a greater understanding of the genetic factors associated with VEOIBD and changed our treatment of these young patients.

Principal investigator:

Dr. Kanya Suphapeetiporn, Head of Medical Genetics and Metabolism Unit, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok

1. Characterization of genes associated with diseases with genetic susceptibility

• Skeletal dysplasia
• Primary immune deficiency
• Inherited epilepsy syndrome

2. Using human induced pluripotent stem cells for modeling genetic diseases

• Wiskott-Aldrich syndrome
• Osteogenesis imperfecta

3. Targeted gene editing in Patient-specific human induced pluripotent stem cells and development of stem cell-based therapy

• Wiskott-Aldrich syndrome
• Osteogenesis imperfecta

Principal investigator:

Dr. Roya Sherkat, Director Acquired Immunodeficiency Research Center, Isfahan University  Hospital

1) Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis

2) Comparative evaluation of cell-mediatetd immunity to cytomegalovirus, in pregnant women with early onset preeclampsia and women with

normal pregnancy

3) Natural killer cell Ig-like receptor (KIR) genes genotypes in patients with chronic hepatitis B , families with hepatitis B and healthy subjects

4) Pregnancy, child bearing and prevention of giving birth to an affected child in Primary Immunodeficiency Disease

5) Genetic and functional evaluation of Th17 cells in patients with susceptibility to Candidiasis

6) Evaluation of B cell maturation antigen (BCMA) expression on B cells as well as counting peripheral blood plasma blast cells in patients with CVID in compare with healthy controls