The Li Lab studies the immunoregulatory mechanisms regulating anti-tumor immunity and autoimmune responses. We are currently pursuing three major projects:

Regulation of anti-tumor immunity by regulatory CD8+ T cells

Previously, we have demonstrated the important role of KIR+CD8+ regulatory T cells in maintenance of peripheral tolerance by suppressing autoreactive T cells. Since a large fraction of tumor antigens is derived from the self, we are curious whether the regulatory functions of KIR+CD8+ T cells extend to anti-tumor immunity. We will leverage cutting-edge technologies, mouse cancer models and patient-derived specimens to understand the role of KIR+/Ly49+CD8+ Tregs in regulating anti-tumor immunity and how their differentiation or functions are regulated by the tumor microenvironment.

Dynamic changes of cell-surface proteomes on tumor-infiltrating T cells

In the field of tumor immunology, a central question that requires further investigation is how T cells ‘talk’ to neighboring cells through signaling at the cellular interface to promote tumor progression. We will use a newly developed technology to profile the dynamic changes of cell-surface proteomes on anti-tumor T cells and regulatory T cells in situ in the tumor microenvironment. We aim to identify new targets to reinvigorate the anti-tumor T cells or suppress the regulatory T cells for cancer immunotherapy.

Understanding the pathogenesis of human Type 1 Diabetes

We are currently working on the analysis of samples obtained from the TEDDY cohort, a study that involves the longitudinal collection of PBMCs from individuals at various stages: before seroconversion, during seroconversion, and up to the onset of Type 1 Diabetes (T1D). Our primary objective is to gain insights into the breakdown of immune tolerance during the progression to T1D and to identify antigenic drivers of T1D. To achieve this, we will monitor the quantitative and phenotypic changes in CD4+ and CD8+ regulatory T cells over time using single-cell RNA sequencing. Additionally, we will be collaborating with Dr. Alok Joglekar to decode the antigen specificities of T cell receptors associated with disease progression.