Grant: Doctoral Research Award: Canada Graduate Scholarships

Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are severe skin reactions, often caused by medications, which can be life-threatening. These conditions cause the skin to blister and peel off, leading to significant pain and risk of infection. Currently, there's no specific treatment for SJS/TEN because we don't fully understand how they develop. Our research focuses on a protein that acts as molecular scissors called Granzyme B (GzmB), which is usually involved in the body's defense against viruses, bacteria, or cancer cells by cutting up the proteins inside the affected cells and leading to cell death. However, in conditions like SJS and TEN, GzmB might accumulate in the space surrounding cells - doing more harm than good. We have seen so far that GzmB levels are high in the blister fluids of SJS/TEN patients and GzmB can cut up proteins that hold the skin layers together, leading to the blistering seen in these conditions. We believe that the proteins cleaved by GzmB might also trigger inflammation, making the condition worse. In our study, we aim to: 1.Understand how GzmB changes the behavior of skin cells by looking at which genes are turned on or off when GzmB is present. 2.Figure out exactly how GzmB damages these key skin proteins and see if the protein fragments it creates can worsen inflammation and delay wound healing. 3.Examine the role of inflammatory molecules which are released in the presence of GzmB. By understanding these processes, we hope to find new ways to treat or even prevent these severe skin reactions by targeting GzmB or the pathways it activates. This could lead to better outcomes for patients suffering from SJS and TEN.