Qianxia Zhang, Ph.D., Postdoctoral Fellow Boston Children's Hospital

The mammalian adaptive immune system relies on a series of intricate selection process on immune repertoires to enforce a robust discrimination between self and non-self, which is the key to prevent autoimmunity. However, since self-antigens are shared in tumor tissues, robust self-tolerance can also limit effective anti-tumor immune responses. Therefore, a clear molecular understanding of how the immune system discriminate self and non-self can provide therapeutic guidance for autoimmune disease and cancer immunotherapies. 

One protein that is important to establish T cell tolerance is Aire (Autoimmune Regulator). Aire is responsible for upregulating more than one-third of self-antigens to be expressed in thymus, so that self-reactive T cells can be eliminated or develop into immunosuppressive regulatory T cells. While the physiological importance of Aire has been well demonstrated, mechanistically how Aire upregulates self-antigens remains elusive. Dr. Hur’s lab has recently discovered that Aire directly interacts with CBP and P300, factors that are known to assist in the regulation of gene expression. Therefore, Dr. Zhang will use a combination of advanced techniques to interrogate the functional consequence of their interaction. She will also identify additional factors that are important for Aire-mediated self-antigen expression. 

In summary, Dr. Zhang’s work may provide direct molecular evidence on how Aire cooperates with other factors to induce T cell tolerance and will link the gap between molecular mechanism and physiological impact of Aire.

Projects and Grants