Tian Lab

@ SYSUCC

The research in the lab focuses on understanding the molecular mechanisms and clinical relevance of tumor microenvironment plasticity. We are particularly interested in how the tissue-resident stromal cells exhibit phenotypic and functional plasticity in response to inflammatory niche factors. Our ultimate goal is to develop better therapeutic strategies that leverage anti-tumor stromal cells to eradicate cancer cells and impair the pro-tumor stromal cells for the benefit of patients.

Cell identity is initiated by lineage-determining factors and is subsequently maintained by niche factors. The formation of a tumor, which creates a deteriorating environment, disrupts tissue homeostasis and alters cellular phenotypes. Consequently, immunostaining alone is insufficient to distinguish the origin of the cells due to the loss of cell identity markers. We developed novel lineage tracing tools (e.g., split-Cre, dual recombinase) to precisely label subsets of tissue-resident stromal cells and investigate their role in tumor progression.

The tumor microenvironment (TME) of overt malignancy is highly complex, making it challenging to delineate and difficult to intervene pharmacologically at later stages. Identifying early tumor-stromal interactions not only provides insights into how cancer cells exploit stromal cells to promote their growth but also reveals potential targets for cancer progression. To elucidate early microenvironmental cell-cell interactions, we employ various niche labeling approaches, including soluble lipid-permeable (sLP) mCherry penetration and SrtA-based biotinylation, in both autochthonous tumor models and experimental metastasis models.

Epigenetic reprogramming, which encompasses the modification of histones and DNA, is critical for phenotypic plasticity and functional alterations. By combining our fluorescent lineage-tracing mouse models, we isolate cells of identical origin from both normal and malignant tissues to explore the epigenetic rewiring in these cells through CITE-seq, SLAM-seq, ATAC-seq, and CUT&Tag-seq.