Student’s Name: Jaclyn Law
Supervisor: Dr. Pamela S. Ohashi, Professor, Department of Immunology
Program: Hon BSc, Immunology Specialist Program, Department of Immunology
My interest in immunology was cemented by my current research project in Dr. Pam Ohashi’s lab at the Princess Margaret Cancer Centre, which was funded in part by an award granted by the Undergraduate Research Opportunity Program. Beginning last summer, my project with the Immunology Department focused on characterizing the genetic signature of functionally exhausted CD8+ T cells. Exhausted CD8+ T cells have impaired effector function due to the upregulated expression of cell surface inhibitory molecules when chronically stimulated by persistent antigen, leading to defective tumour and viral clearance. Thus the ability to identify and reverse exhaustion are imperative in treating disease. These cell surface molecules are frequently used to identify exhausted T cells; however, their reliability as markers has been contested due to their confounding expression on recently activated T cells.
Using qPCR and methylation-sensitive high resolution melting analysis on DNA isolated from LCMV challenged T cells in a pilot project to examine DNA methylation patterns of exhaustion, I have identified more than two novel epigenetic markers unique to the exhausted T cell subset, and present a potentially more accurate way of tracking differential T cell activation states.
Following this exciting discovery, my work has since expanded for my Honour’s thesis project to include the assessment of methylation inhibitors as potential therapeutics for the functional rescue of exhausted T cells through epigenetic reprogramming. Another facet of my project with the Ohashi lab involves the optimization of a 12 colour flow cytometry panel to serve dual purposes: the first is to heighten the precision with which we identify exhausted cells using surface markers, and the second is to examine the extent of exhaustion based on the accumulation or combination of these markers.
Presentation of my findings has earned me 3rd place at the annual Ontario Quebec Undergraduate Immunology Conference hosted by the University of Toronto.
In culmination of my project, this summer I will be focusing on the functional effects of methylation inhibitors on lymphocyte exhaustion using both an in vivo and in vitro approach, and subsequent genetic modifications post-treatment. I will also be investigating the functional consequences of genetic knock downs of the epigenetic markers we have identified.
I have since developed a strong interest in immunological signal transduction pathways in lymphocytes as a result of my project, especially in the contribution of lymphocyte dysregulation to infectious disease susceptibility and progression, and viral-host interaction. I hope to further pursue this topic when I begin my Master’s program with the Department of Immunology September 2016, for which I have been awarded the Merit Entrance Scholarship by the Faculty of Medicine.
I have earned a 4.0 GPA (90+) across all immunology courses throughout my undergraduate degree. Outside of science, I have been an annual recipient of the UofT Dean’s List, as well as a recipient of in-course scholarships from Trinity College.