教育背景
1995–2000 北京中医药大学 医学/学士
2003–2005 荷兰乌特勒支大学 化学/硕士
2005–2010 荷兰莱顿大学 物理/博士
工作经历
2010-2013 中国科学院化学研究所 博士后
2013-2024 清华大学医学院 副研究员
2024-至今 清华大学基础医学院 副研究员
研究领域
细胞膜的外界感知和跨膜信号传导。研究聚焦在真核细胞膜上的脂质分子与蛋白质受体之间的相互作用。经典的细胞膜受体激活理论是以配受体识别，即蛋白质-蛋白质互作为中心的。然而越来越多的实验数据证实在没有配体分子存在的情况下，受体分子可以自发激活。这种非配体依赖的受体激活通常发生在脂质微环境发生改变的情况下，这就提示脂质分子在受体激活过程中扮演了重要角色。因此，经典的以蛋白质为中心的受体激活理论需要完善和补充，而以蛋白质和脂质分子互作为基础的受体激活理论应该得到应有的审视。借助先进的生物物理手段，一方面可以在单分子水平，原位表征受体的聚集和运动状态，另一方面，通过体外重构跨膜蛋白与脂质胶束复合物，利用液体核磁表征受体跨膜的结构及脂质分子构成对其的影响。最终，希望可以全面的理解真核细胞膜上的受体激活全貌。
科学贡献
在细胞膜感知外界固体颗粒方面，参与发现了基于细胞膜脂质分子(PIP2)感知而触发的新型吞噬作用的分子机理，并找到该信号通路中将膜上信号转导至胞内信号的重要分子Moesin（nature communication 2018）。PIP2-moesin-syk这条古老且保守的吞噬信号通路，应该是后出现的FcR信号通路的物质基础。然而，这种基于膜感知的古老信号通路仍旧被保留至今，当吞噬细胞遇到非生物性固体颗粒，这套系统仍然继续发挥它的余热。
在微生物对宿主免疫调控方面，参与揭示了绿农杆菌分泌的群集感应信号分子通过对宿主细胞膜脂筏结构的破坏，实现调控宿主免疫信号的分子机制(Nature Microbiology 2019)。由于受体的激活常常受到脂筏调控，脂筏的结构破坏会引起受体的自发多聚而激活下游信号。绿农杆菌利用自身分泌的群集感应信号分子干扰宿主免疫细胞膜上的脂筏结构，引起死亡受体非配体依赖的自发激活，导致宿主免疫细胞的死亡，从而使自身更好的在宿主中存活。该研究很好的佐证了受体可以不依赖配体而自发激活，而这种自发激活受到脂质分子的调控。
在免疫耐受方面，通过力学效应角度，参与发现并揭示了调节性T细胞（Treg）发挥免疫机制的核心机理，即Treg和DC之间有很强的结合力，这个强结合力造成DC内细胞骨架在细胞接触面的极化富集，阻止了其向其他T细胞进行抗原呈递，从而抑制了免疫反应的发生（JEM 2017）。后续，又将整个（在T细胞中）调控T cell/DC结合力的信号通路完整的解析出来（JCI 2023），为未来开发Treg免疫治疗打下了理论基础。
荣誉奖励
2011 中国博士后科学基金面上资助二等（No.20110490604）
2010 中国科学院王宽诚博士后工作奖励基金
代表性论文
1.Li S, Huang F, Xia T, Shi Y, Yue T* (2023) Phosphatidylinositol 4,5-Bisphosphate Sensing Lipid Raft via Inter-Leaflet Coupling Regulated by Acyl Chain Length of Sphingomyelin, Langmuir 39: 5995-6005.
2.Yang C, Wang X, Xie R, Zhang Y, Xia T, Lu Y, Ye F, Zhang P, Cao T, Xu Y, Fan Q* (2023) Dynamically Reconstructed Collagen Fibers for Transmitting Mechanical Signals to Assist Macrophages Tracing Breast Cancer Cells, Advanced Functional Materials 33:9.
3.Xu Y, Song D, Wang W, Li S, Yue T, Xia T, Shi Y* (2023) Clec12a inhibits MSU-induced immune activation through lipid raft expulsion, Life Science Alliance 6:9.
4.Lyu H, Yuan G, Liu X, Wang X, Geng S, Xia T, Zhou X, Li Y, Hu X, Shi Y* (2023) Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs, eLife 12:257-277.
5.Wang X, Geng S, Meng J, Kang N, Liu X, Xu Y, Lyu H, Xu Y, Xu X, Song X, Zhang B, Wang X, Nuerbulati, Nuerdida, Zhang Z, Zhai D, Mao X, Sun R, Wang X, Wang R, Guo J, Chen, S R Wayne, Zhou X, Xia T, Qi, H, Hu X, Shi Y* (2023) Foxp3-mediated blockage of ryanodine receptor 2 underlies contact-based suppression by regulatory T cells, The Journal of clinical investigation 133:24.
6.Ruan H, Zou C, Xu Y, Fang X, Xia, T*, Shi Y* (2022) N-(3-Oxododecanoyl) Homoserine Lactone Is a Generalizable Plasma Membrane Lipid-Ordered Domain Modifier, FRONTIERS IN PHYSIOLOGY 12:257-277.
7.Xu S, Liu Y, Cernava, Tomislav, Wang H, Zhou Y, Xia T, Cao S, Berg, Gabriele, Shen X, Wen Z, Li C, Qu B, Ruan H, Chai, Y, Zhou X, Ma Z, Shi Y, Yu Y, Bai Y, Chen Y* (2022) Fusarium fruiting body microbiome member Pantoea agglomerans inhibits fungal pathogenesis by targeting lipid rafts, Nature Microbiology 7:831-843.
8.Liu L, Yu H, Zhao H, Wu Z, Long Y, Zhang J, Yan X, You Z, Zhou L, Du Y, Wang Y, Xia T, Shi Y, Xiao B, Huang C* (2020) Matrix-transmitted paratensile signaling enables myofibroblast-fibroblast cross talk in fibrosis expansion, Proceedings of the National Academy of Sciences of the United States of America 117:10832-10838.
9.Luo, F, Qin, G, Xia, T, Fang X* (2020) Single-Molecule Imaging of Protein Interactions and Dynamics, ANNUAL REVIEW OF ANALYTICAL CHEMISTRY 13:337-361.
10.Song D, Meng J, Ruan H, Kang N, Xu Y, Wang X, Shu F, Mu L, Li T, Ren W, Lin X, Xia T, Shi Y, Cheng J, Lyn J, Fan Z, Wu W, Chen P, Yan L, Tu Z, Li N, Fang X, Zhu J, Amrein, Matthias W.* (2019) Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution, Nature Microbiology 4:97-111.
11.Chen J, Xu Y, Shi Y, Xia T* (2019) Functionalization of Atomic Force Microscope Cantilevers with Single-T Cells or Single-Particle for Immunological Single-Cell Force Spectroscopy, JOURNAL OF VISUALIZED EXPERIMENTS 2019:146
12.Zhao R, Yuan J, Li N, Sun Y, Xia T, Fang X* (2019) Analysis of the Diffusivity Change from Single-Molecule Trajectories on Living Cells, Analytical Chemistry 91:13390-13397.
13.Shu F, Chen J, Ma X, Fan Y, Yu L, Zheng W, Amrein M, Xia T, Shi Y* (2018) Cholesterol Crystal-Mediated Inflammation Is Driven by Plasma Membrane Destabilization, FRONTIERS IN IMMUNOLOGY 9:1163.
14.Mu L, Tu Z, Miao L, Ruan H, Kang N, Hei Y, Chen J, Wei W, Gong F, Wang B, Du Y, Ma G, Amerein, M, Xia T*, Shi Y* (2018) A phosphatidylinositol 4,5-bisphosphate redistribution-based sensing mechanism initiates a phagocytosis programing, NATURE COMMUNICATIONS 9:4259
15.Qi C, Li Y, Badger P, Yu H, You Z, Yan X, Liu W, Shi Y, Xia T, Dong J, Huang C, Du Y* (2017) Pathology-targeted cell delivery via injectable micro-scaffold capsule mediated by endogenous TGase, BIOMATERIALS 126:1-9.
16.Liu L, You Z, Yu H, Zhou L, Zhao H, Yan X, Li D, Wang B, Zhu L, Xu Y, Xia T, Shi Y, Huang C, Hou W, Du Y* (2017) Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis, NATURE MATERIALS 16:1251-1261.
17.Amrein M, Xia T, Shi Y* (2017) Other modern methods for studying biomembranes, Membrane Biophysics: New Insights and Methods 393-421.
18.Chen J, Ganguly A, Mucsi A D, Meng J, Yan J, Detampel P, Munro F, Zhang Z, Wu M, Hari A, Stenner M D, Zheng W, Kubes P, Xia T, Amrein M, Qi H, Shi Y* (2017) Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy, Journal of Experimental Medicine 214:327-338.
19.Wang B, Qin P, Zhao H, Xia T, Wang J, Liu L, Zhu L, Xu J, Huang C, Shi Y, Du Y* (2016) - Substrate stiffness orchestrates epithelial cellular heterogeneity with controlled proliferative pattern via E-cadherin/β-catenin mechanotransduction, Acta Biomaterialia 41:169-180.
20.Luo W, Xia T, Xu L, Chen Y, Fang X* (2014) Visualization of the post-Golgi vesicle-mediated transportation of TGF-beta receptor II by quasi-TIRFM, JOURNAL OF BIOPHOTONICS 7:788-798.
21.Xia T, Yuan J, Fang X* (2013) Conformational dynamics of an ATP-binding DNA aptamer: A single-molecule study, Journal of Physical Chemistry B 177:14994-15003.
22.Xia T, Li N, Fang X* (2013) Single-Molecule Fluorescence Imaging in Living Cells, ANNUAL REVIEW OF PHYSICAL CHEMISTRY 64:459-480.
23.Yuan H, Xia T, Plazanet M, Deme B, Orrit M* (2012) Communication: Crystallite nucleation in supercooled glycerol near the glass transition, JOURNAL OF CHEMICAL PHYSICS 136:041102
24.Yuan H, Xia T, Schuler B, Orrit M* (2011) Temperature-cycle single-molecule FRET microscopy on polyprolines, PHYSICAL CHEMISTRY CHEMICAL PHYSICS: 13:1762-1769.
25.Kulzer F, Xia T, Orrit M* (2010) Single Molecules as Optical Nanoprobes for Soft and Complex Matter, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION 49:854-866.
26.Möbius M, Xia T, van Saarloos W, Orrit M, van Hecke M* (2010) Aging and Solidification of Supercooled Glycerol, JOURNAL OF PHYSICAL CHEMISTRY B 114:7439-7444.
27.Xia T, Xiao L, Orrit M* (2009) Micron-Sized Structure in a Thin Glycerol Film Revealed by Fluorescent Probes, JOURNAL OF PHYSICAL CHEMISTRY B 113:15724-15729.
28.Zondervan R, Xia T, van der Meer H, Storm C, Kulzer F, van Saarloos W, Orrit M* (2008) Soft glassy rheology of supercooled molecular liquids, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 105:4993-4998.
