Doctoral Research

During my PhD research, I studied the mechanism of focused secretion of T cells. Focused secretion lies at the heart of T cell effector functions. It requires movement of the microtubule organizing (MTOC) center to the immune synapse and movement of secretory vesicles towards the MTOC. Without focused secretion, the ability of CTLs to clear pathogens and tumor cells is impaired. Yet the mechanism is unknown and controversial to some extent.  I found that MTOC translocation is accomplished through the association of dynein, a motor protein with NDE1/Lis1, whereas the dynein-dynactin complex is required for vesicle clustering. NDE1 is a neurodevelopmental protein that was never studied before to have role in T cell effector function. I further show that NDE1 localization at the synapse occurs in the absence of dynein but is essential for recruitment of dynein to the immunological synapse. Thus NDE1 provides a key link in establishing polarity for focused secretion. Moreover, I identified DISC1, a protein that is mutated in schizophrenia, to be recruited at the synapse formed by T lymphocytes (see image below). This suggest a possible link between schizophrenia and immune-dysfunction. The work was published in the Journal of Immunology.