肝细胞癌尤其是HBV阳性肝癌是我国重大疾病。申报人研究方向为肿瘤微环境调节肝癌血管转移及分子机制。结合肿瘤转移、天然免疫以及血管生物学方面研究背景，探讨HBV阳性肝癌中微环境的调控机制。研究成果包括：①发现天然免疫识别蛋白Lrrfip1 及其信号途径；②阐明肝癌中免疫微环境介导的肝癌门静脉血管转移机制，发现Treg亚群迁移新途径；③发现间充质干细胞改变肿瘤微环境新机制；④找到肝癌转移的SPECT检测探针和血管转移新分子。相关工作以第一（含并列）或共同通讯作者在Nat Immunol、Cancer Cell、Nat Cell Biol等杂志发表论文16篇，他引577次，单篇最高他引126次。获明治生命科学奖和美国杜克大学Fitzgerald学者奖，2013年入选青年千人。本项目拟结合多种血管转移和成像技术平台，集中研究新标志分子参与肝癌微环境、血管转移等机制，以期发现肝癌转移新诊断治疗靶标。

Hepatocellular carcinoma (HCC), especially HBV-associated HCC, is an important disease in China. My major research interests are the molecular mechanisms and immune control in the HBV-associated tumor microenvironment during the process of vascular metastasis. On the basis of my experience on cancer metastasis, innate immunology and vascular biology, my research has built interests on the mechanisms underlying this special HBV-associated tumor immune microenvironment. My previous finding includes: 1. found a new cytosolic nucleic acid sensor LRRFIP1, which mediates the production of type I interferon via a beta-catenin dependent pathway (Nature Immunology, 2010); 2. uncovered a causative link between HBV infection and development of portal vein tumor thrombus, which recruits regulatory T cells to tumor microenvironment (Cancer Cell, 2012); 3. found a pathway that regulates the recruitment of mesenchymal stem cells and inflammatory monocytes into the tumor stroma (Nature Cell Biology, 2013); 4. developed new radiotracers for SPECT monitoring of HCC metastatic site, and new molecules related with vascular metastasis. I am the first (including co-first) or co-corresponding author within 16 SCI research articles, including the journals of Nature Immunology, Cancer Cell and Nature Cell Biology. In 2013, I was elected as a member of Youth 1000-plan in China. In this study, we will investigate the functions and mechanisms of our new-found molecules that contribute to HCC progression and vascular metastasis, with exploiting our SPECT monitoring probes and vascular inflammatory model. This project represents our efforts in both translating the earlier findings into a potential therapeutic strategy and understanding new mechanistic functions in HBV-associated HCC development.