Professor and doctoral supervisor of Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Director of Stem Cell Clinical Research Quality Control laboratory, Peking Union Medical College Hospital. Her research expertise is in the tissue repair and reconstruction, based on cross disciplines such as stem cell frontier technology, multiomics, and histopathology, forming independent and innovative core technologies such as complex skin organoid construction and spatial proteomics.

Topic title: Construction and Application of Complex Skin Organoid

Abstract:

Xeroderma pigmentosum (XP) is a rare disease with birth defects. Due to a lack of DNA damage repair enzymes, patients receiving sunlight can trigger incorrect damage repair mechanisms and accumulate mutations, leading to basal tumor development. XP patients usually die before the age of 10, and there is currently no cure. In previous, we firstly established the strategy of spatial quantitative proteomics by combining decellularization, laser-capture microdissection, and mass spectrometry. Using the strategy, we successfully established a complete hierarchical skin proteome map and analyzed the specific function of different structures of normal and dermatologic skin tissues in situ. We found TGFβ induced (TGFBI), a glycoprotein of epidermal stem cells (EpSCs)’ niche, enhance the growth and function of EpSCs and promotes the process of wound healing. In this study, we utilized spatial proteomics methods to establish proteomic maps of XP skin EpSCs and their niches, and discovered new mechanisms for DNA damage repair during the development of the tumors from XP. In addition, we utilized the previously established skin organoid model to construct a human-induced pluripotent stem cell (hiPSC) derived XP skin organoid model from XP patients and a PDX model derived from XP organoid transplant mice. By combining multidimensional omics techniques such as single-cell transcriptome and spatial proteomics, as well as physiological, pathological, and molecular biology methods, we identified therapeutic targets for skin basal carcinoma in XP patients. Finally, we discovered a potential small molecule drug that can serve as a preventive measure against XP tumors after surgery.