In the last installment, I discussed some of the exciting research featured at the Neuroinflammation Symposium that really highlights the breadth and diversity of expertise in the field of MS, both here in Canada and abroad. The trainees in particular were a true source of pride and inspiration, and the quality of their work is emblematic of the importance of cultivating talent and collaboration in the field by attracting and retaining the brightest minds and providing a forum for sharing ideas.
During this year’s research poster presentations, three trainees were selected from the pool of excellent candidates by a panel of judges for having the most meritorious research posters. These winners were:
- Kirsten Fiest (University of Manitoba)
- Dessalegn Melesse (University of Manitoba)
- Linda Fei Zhao (University of Toronto)
In this post, I will be profiling Ms. Linda Fei Zhao, doctoral student in Dr. Shannon Dunn’s laboratory at the University of Toronto and MS Society-funded trainee. Ms. Zhao’s research focus is on identifying novel drug targets for the purposes of influencing the development of harmful immune cells and deterring autoimmunity, a critical component of the MS disease process. I had a chance to catch up with Ms. Zhao and chat a little bit about her research and its impact for people living with MS, as well as how her experiences at the Neuroinflammation Symposium have influenced her research career.
1. Describe the research that you presented in your poster.
Multiple sclerosis is an autoimmune disease where specific immune cells called T cells attack myelin in the brain, leading in turn to progressive disability. My project aims to understand how a specific chemical receptor that has anti-inflammatory properties – called peroxisome proliferator-activated receptor delta (PPARδ) – keeps these T cells at bay. We found that when we shut off PPARδ in mice with an MS-like disease, they experience more severe disease symptoms. These PPARδ-deficient mice have defective T cell development in the thymus (a specialized organ of the immune system where T cells mature), as well as low white blood cell count, which makes them more susceptible to autoimmunity. We also found that this defect appears to be caused by specific non-immune cells called thymic epithelial cells. When we remove PPARδ specifically from thymic epithelial cells, we saw similar defects in T cell development in the thymus. Taken together, these findings indicate that PPARδ may impact the development of autoimmunity in the central nervous system at the earliest stages of T cell development.
2. What is the impact of your research for people affected by MS?
T cells that are involved in the MS disease process develop in the thymus, where multiple cell types, including thymic epithelial cells, “train” T cells not to attack one’s own body. The resulting T cells that leave the thymus are considered to be “tolerant” to the body’s own cells. However, this training process is not perfect, and self-reactive T cells (so called because they attack the body’s own tissues) can escape elimination and, in the case of MS, end up targeting myelin in the brain. Therefore, finding new genes that are responsible for maintaining tolerance is a crucial step in the development of new drugs to prevent autoimmune diseases. We have found that the anti-inflammatory molecule PPARδ regulates T cell development by affecting thymic epithelial cells. Without PPARδ, mice have abnormally low numbers of white blood cells, a state called lymphopenia that can potentially bring on autoimmune disease. Our work helps to shed light on how these harmful T cells that may cause MS and other autoimmune diseases are generated as well as open up new avenues for preventing the development of autoimmune T cells.
3. What feedback did you receive from other researchers when you presented your poster and how may that feedback influence future directions of your study?
One of the judges mentioned that iron receptor-deficient mice do not get experimental autoimmune encephalomyelitis (EAE), a disease in mice that mirrors the signs and symptoms of MS. This is very interesting because the iron receptor in question, called CD71, is crucial during T cell development and expansion during an immune response. Without iron receptors, T cells do not receive sufficient nutrients to grow and divide, which may contribute to EAE resistance in iron receptor-deficient mice. Perhaps, the lack of iron receptor may also be limiting the development of self-reactive T cells. This comment that I received made me aware of other implications of my work and pointed out new interesting research questions that can guide my project.
Another common question I receive all the time is how will my research help people with living MS. As a person working in the field of basic sciences, it is easy to get carried away by the bench work. This crucial question has constantly reminded me of why I am doing research in the first place. It also reminds me to make sure that I ask questions that may be translatable, from bench to beside, in the future.
4. How have the Neuroinflammation Symposium and other similar events opened up new networking opportunities and avenues for collaboration between you and other MS researchers?
I have been deeply involved with the MS Society of Canada for many years. The MS Society has supported me in attending numerous conferences and endMS Summer Schools. These opportunities have allowed me to meet world-leading MS researchers, as well as young trainees like myself. I have received helpful feedback from them that provided me with fresh perspectives on my research. These events kept me up-to-date with the cutting edge research in the MS field and exposed me to new techniques that I can incorporate into my research.