Yisong Wan

Job Description

The overarching goal of our research is to uncover critical mechanisms underlying T cell function in immune homeostasis, immunological aging, immunity, and immune diseases including autoimmunity and cancer.

1. Function and regulation of Treg cells
   Treg cells, a CD4 T cell subset that specifically express a transcription factor Foxp3, are critical to the suppression of immune responses and anti-tumor immunity. We found that a transcription factor GATA-3 is highly expressed in Treg cells and controls Treg cell function and immune homeostasis (Immunity 2011). In addition, we found that GATA-3 is fundamental for T cell maintenance, metabolism and proliferation downstream of TCR and cytokine signaling (Nature Immunology, 2013). Moreover, we discovered novel factors including DCAF1 (Nature Communications, 2016) and BPTF (Journal of Immunology, 2016) critical for Treg cell function. We are currently identifying the factors and mechanisms critical for Treg cell function in tolerance, tumor and aging.
2. TGF-beta signaling in T cells
   Initially identified as a tumor promoting factor, transforming growth factor beta (TGF-beta) is essential for immune suppression and tumor immune evasion. TGF-beta activates Smad- and MAPK-dependent pathways to control cellular function. We found these pathways play distinct roles in Treg and non-Treg cells (PNAS 2016). In addition, we revealed an unexpected TGF-beta-independent function of Smad4 in controlling T cell mediate autoimmunity and tumor rejection (Immunity 2015). Furthermore, we discovered a novel TGF-beta/SKI/Smad4 dependent pathway in controlling the function of Th cells for autoimmunity (Nature 2017). We are investigating how this new pathway is critically involved in pathogen clearance, inflammation, autoimmunity and anti-tumor immunity.
3. Molecular networks underlying T cell function during normal physiology and disease
   We have been studying the functional proteomes during T cell function. One of our main goals is to use cutting-edge mass-spectrometry based proteomic analysis to elucidate the protein-networks underlying T cell function. We have been analyzing the protein expression profiles and protein-protein interaction networks during T cell growth, quiescence exit, proliferation and differentiation in a global fashion. Such an approach has been quite effective in uncovering previously unappreciated critical factor for T cell proliferation and differentiation (Nature Communications 2016, Nature 2017, Immunity 2018). By combing genomic, epi-genomic and epi-proteomic analysis, we are obtaining a more detailed information the molecular network underlying T cell function to pinpoint the critical factors and molecular targets for immune regulation and diseases.