申请人任研究组长，发现了癌蛋白Gankyrin作为肝脏炎-癌转化的重要中介分子（Hepatology 2015，Cell Research 2007,2009），调控肝癌干细胞影响预后和耐药，可作为肝癌治疗新靶标（Gastroenterology 2012，Hepatology 2011, Autophagy 2015）；并开展其抗体和小分子抑制剂研制应用研究（申请专利3项）。发表第一作者和通讯作者（含并列）SCI论文10篇，影响因子10以上6篇。NAFLD是肝癌独立危险因素之一，机制尚不明确；其中癌基因和抑癌基因失调与脂代谢紊乱相关。斑马鱼肝内高表达Gankyrin可引发脂肪肝；而Gankyrin是Ras下游应答分子之一。Kras可引起脂代谢紊乱导致胰腺癌；肥胖相关肝癌可能与Ras通路活化有关。因此，我们将运用转基因小鼠研究两者对NAFLD影响，阐述癌基因引起的肝病与脂代谢紊乱间的联系。

The applicant is, a group leader, focused on the mechanism of hepatocarcinogenesis and progression, and study the role of oncoprotein Gankyrin/p28GANK in HCC. We identified oncoprotein Gankyrin as a novel effector linking hepatic inflammation to HCC initiation. Our finding of IL-1β/IRAK-1 signaling promoting Gankyrin expression through JNK and NF-Y/p300/CBP complex provides a fresh view on inflammation-enhanced hepatocarcinogenesis (Hepatology 2015) . Moreover, Gankyrin prevents degradation of Oct4 and promotes expansion of tumor-initiating cells in hepatocarcinogenesis (Gastroenterology 2012), accelerates hepatocellular carcinoma invasiveness and metastasis (Hepatology 2011), and encourages autophagy to enhance drug resistance (Autophagy 2015). All of the above mentioned findings provide Gankyrin as a novel target for HCC therapy. Therefore, preparation and identification of monoclonal antibodies and small molecular inhibitors for Gankyrin have been performed (3 patents in application). Eleven papers in SCI-tech journals have been published as the first author or the corresponding author (including co-first and co-corresponding author). There are six articles published on the journals with impact factor greater than 10, all of which was labelled by a first or corresponding author (including co-first or co-corresponding author) ..Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor of Hepatocellular carcinoma (HCC), but the mechanism remains unclear. Activated oncogenes or loss of tumor suppressors appear to “softwire” cancer genes to metabolism, since metabolic enzymes are directly regulated by these cancer genes. It has been reported that overexpresison of gankyrin induces liver steatosis in zebrafish. High-fat-diet (HFD)-mediated Kras activation promotes prostate carcinogenesis dependently of obesity. HFD consumption, in conjunction with Kras mutation, accelerated HCC progression. Gankyrin plays an essential role in Ras-induced tumorigenesis. Thus, we will use a series of transgenic mice to study the effects of both oncogenes on NAFLD, and transformation from NAFLD to NASH to HCC, which will provide a potential therapeutic target in NAFLD.