Sonia Dalal, Biological Sciences
“Determine the Mechanism CD80 Uses to Activate T-Cells and Induce Immunity in Individuals with Cancer”
Programmed Death Ligand-1 (PD-L1) is expressed by many tumor cells and increases tumor progression by binding to its receptor PD-1 on T-cells, thereby inhibiting T-lymphocyte activation and causing T-cell apoptosis. Cluster of Differentiation 80 (CD80), expressed by antigen presenting cells provides a potent costimulatory signal needed for T-cell activation by binding to T-cell-expressed CD28. We have recently identified another function for CD80 and shown that human cancer cells modified to express CD80 inhibit PD-L1 binding to its receptor, resulting in increased T-cell activation. To distinguish if tumor cell-expressed CD80 promotes T-cell activation by binding to CD28 and/or inhibiting PD-L1 we must construct a mutant CD80 that does not bind to CD28. We are generating a soluble CD80 mutant (sCD8096,97,99) because it is not feasible to inject cancer cells expressing CD80 into patients. Previous studies demonstrated that CD80 mutated at amino acids 96. 97, and 99 (CD8096,97,99) no longer binds CD28. To generate a mutant soluble molecule the sCD8096,97,99 gene was inserted into the pINFUSE-hIgG1-Fc vector. Mammalian cells are being transfected with the sCD8096,97,99 construct. sCD8096,97,99 will be purified and western blot analyzed and used in functional experiments to determine how CD80 restores T-cell activation.
How did you find your mentor for your research?
As a freshman entering UMBC, I hoped to pursue cancer research and learn related laboratory techniques. I read about professors’ research in the Biological Sciences Department and then emailed professors about research I was interested in. The Meyerhoff Scholarship Program helped me to get involved in research as early as the first summer after my freshman year and I have been working in Dr. Rosenberg’s Laboratory ever since.
How did you know this was the project you wanted to do?
Since I have a strong interest in focusing my future research endeavors on cancer biology and related fields, this project fit into my goals perfectly.
Is this your first independent research?
Though I had some research experience with NASA in high school, this was my first independent research project. It proved to be very fulfilling as I was able to learn many of the basic and advanced laboratory techniques necessary for a competent scientist.
Do you get course credit for this work?
Yes, I receive two or three pass/fail credits per semester.
How much time do you put into it?
Working on my research excited me and I put in about 15-20 hours per week during the academic year. During the summer and winter breaks I spent about 40 hours per week in the lab.
What has been the hardest part about your research?
Before working in Dr. Rosenberg's laboratory I believed that research was "black and white." I learned that research requires accepting many failed experiments. Working in the Rosenberg laboratory has allowed me to learn that although failure is a part of research, it will be overcome with experience. I have also learned how to work with graduate students and post doctoral researchers in a competitive and fast-paced environment.
What are your career goals?
I hope to pursue a M.D./Ph.D. due to my strong desire to perform research and identify solutions that benefit people.