Areas of Interest
I am interested in manipulating signaling pathways in T cells to understand their behavior in the setting of cancers for the development of new immunotherapy strategies. My project focuses on manipulating antigen recognition of T cells to boost their reactivity against tumors bearing low- affinity antigens. To achieve this, I aim to target a membrane-proximal machinery in T cell receptor (TCR) signaling, Lck kinase. Lck is critical in setting the threshold of T cell activation since it phosphorylates ZAP70 to initiate TCR signaling cascade. It has been found that Lck is basally active prior to antigen recognition by T cells, and its basal activity affects discrimination in antigen recognition. Typically, antigens of low affinity for TCRs generate weaker responses. Immunoediting of some malignancies generate tumors that possess antigens of low-affinity or less abundancy, making them poorly immunogenic, which thwarts some patients from responding to current checkpoint therapies. Our lab has developed a virus-derived Lck activator. I aim to use it to sensitize T cells against low-affinity antigens in vivo and boost their anti-cancer responses against poorly immunogenic tumors.