Grant: Doctoral Research Award: Canada Graduate Scholarships

Primary immunodeficiency diseases (PIDs) are a group of rare genetic disorders in which the immune system is broken or missing at birth. Since the immune system is our primary defense against germs such as bacteria and viruses, this leaves affected patients much more vulnerable to developing life-threatening infections. Patients with PIDs face frequent health issues and often develop severe and devastating illnesses that are difficult to cure. Thus, studying how these gene defects cause disease can drastically improve patient treatment and quality of life. Recently, our lab identified various children presenting with recurrent infections and severe inflammation affecting multiple parts of the body. Examining their genetic make-up using sophisticated next-generation DNA sequencing uncovered that they are some of the first patients ever found to have disabling mutations in genes called CARD11 and MALT1. These genes usually cooperate with another gene called BCL10 to form the CBM complex, which is a critical regulator of immune cell function. Consequently, patient immune cells developed abnormally and were unable to respond efficiently to foreign invaders. However, how this complex mediates these processes and diseases is not well understood in humans. In the proposed research, we will work to carefully understand how deficiencies in these genes disable normal protective immune function by measuring the numbers and activity of key immune cells. As these are some of the only cases of CARD11 and MALT1 deficiency ever discovered, this study will not only benefit affected patients, but will broadly inform the development and implementation of therapy for other related diseases in the future.