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The Washington Research Foundation Fellowship

Bryn Smith, Microbiology, 2012-13 WRFF

Bryn SmithI have always had a love for science and knew it would be my focus at UW. As I progressed through the prerequisite science classes, I realized my interest in science lies in the specific processes that play into the larger system. It was my sophomore year, and in addition to declaring a major in Microbiology, I was hired as an undergraduate research assistant in Dr. Carol Miao's lab at Seattle Children's Research Institute. Dr. Miao's lab focuses on increasing the efficiency of Hemophilia treatments via gene therapy and immunomodulation techniques. The immunology side of the lab's research ties into my interests well - it delves into specific pathways in the immune system, but still focuses on the larger picture of treating patients affected by the condition.

I have been lucky to receive outstanding training and guidance in working with mouse models and immunology lab techniques to answer questions in immunomodulation. Now, as a senior, I am working on my own project in the lab utilizing these techniques. Being a part of the Miao lab has also exposed me to different areas of research, such as gene therapy, and has given me a more complete idea of the work that goes into discovering new treatments for diseases. In the future, I plan to pursue a PhD in Immunology or a related biomedical science. I am extremely thankful for the support of the Washington Research Foundation and the dedication they have to encouraging scientific discovery.

Mentor: Carol H. Miao, Pediatrics

Project Title: In vitro expansion of factor VIII-specific T regulatory cells

Abstract: Hemophilia A patients have a deficiency of factor VIII, a protein necessary for the formation of blood clots. Treatment usually involves infusions of replacement clotting factor, but about one-third of patients develop inhibitors to the clotting factor, resulting in reduced efficacy of the infusion. Inhibitors can develop at any time and greatly increase the cost of treatment. T regulatory (Treg) cells have been well characterized in their role of reducing an immune response to an antigen. Additionally, their proliferation in vivo in response to treatment with IL-2 has been studied previously in the Hemophilia A mouse model by the Miao lab. This research project aims to expand factor VIII-specific CD4+CD25+ Treg cells in vitro by costimulation with anti-CD3 and anti-Crry, accompanied by IL-2 treatment. The desired result is an increased number of Tregs that maintain Foxp3 expression and suppressive ability in order to have the same functionality as naturally derived Tregs. Expansion of these antigen-specific cells has implications for further experiments in the adoptive transfer to naive Hemophilia A mice in order to limit the development of inhibitor titers and increase efficacy of factor VIII treatment. This method of treatment has translational potential for treating human patients with hemophilia for long-term results.