Yangyang Li, PhDAssistant Professor

 The dysfunction of T cell immunity and metabolism leads to severe inflammatory diseases. To clarify the regulatory mechanisms of T cell dysfunction, we utilized single-cell multi-omics sequencing, COMPASS analysis, ¹³C labelled metabolic flux, CUT&RUN-seq and murine disease models, and achieved major findings including: (1) Insulin signaling regulates the development and function of adipose regulatory T (Treg) cells to further modulate the progression of obesity and ageing (Nat Immunol 2021; Eur J Immunol 2022) and simultaneously activates transketolase expression in hepatocytes to promote MAFLD by limiting inosine-induced mitochondrial activity (Cell Metab 2024); (2) Glycolytic Th17-like Treg cells promote T cell exhaustion and colorectal cancer (Gastroenterology 2021); (3) The metabolite Gallic acid induces the generation of Th1-like Treg cells to prevent T cell exhaustion and colorectal cancer (Nat Commun 2016; J Immunother Cancer 2022). However, systematic investigation of metabolic factors that regulate the crosstalk between CD8⁺ T and Treg cells and their function remains uncommon. Therefore, we will try to identify tumor antigen-specific CD8⁺ T cells and maintain their persistence in tumor microenvironment. These efforts will help to provide strategic basis for clinical intervention and therapy of cancer.

We will carry out the following studies:

(a)Identify tumor antigen-specific CD8⁺ T cells based on their unique metabolic hallmarks;

(b)Explore metabolic and transcriptional circuits that enable CD8⁺ T cells to overcome Treg-mediated immune suppression in tumor microenvironment;

(c)Dampen the immunosuppressive and tumorigenic effects of Treg cells by targeting key metabolic enzymes.