申请人长期从事糖尿病及其血管病变的发病机制的研究，主要成果如下：1）发现特异性抑制肠道核受体法尼醇X受体（FXR）可以显著改善糖尿病发生，进一步找到了其内源性抑制物--牛黄β鼠胆酸，最终开发出新型肠道特异性FXR拮抗剂用于糖尿病的防治，该成果申请了美国专利；2）揭示抑制脂肪组织缺氧诱导因子1（HIF1）可以作为治疗糖尿病的新靶标，该成果申请了国际专利；3）发现高同型半胱氨酸血症是胰岛素抵抗的独立危险因素。共发表SCI论文26篇，他引191次，其中作为第一作者发表SCI论文8篇，包括J Clin Invest.，Nat Commun.，Diabetes等，平均影响因子8.3，他引132次。主持科研基金3项。本项目拟研究鞘脂神经酰胺代谢网络调控在糖尿病血管病变进程中的作用，揭示抑制肠道FXR可能作为糖尿病血管病变的防治新靶点，进一步筛选和评估特异性抑制肠道FXR药物对糖尿病血管病变的潜在疗效。

My research interests are mainly focused in the field of the pathogenesis of type 2 diabetes and its vascular complications. My main academic achievements included: 1) I found that intestinal specific FXR inhibition could significantly improve diabetes, further identified endogenous FXR antagonist T-βMCA, and eventually discovered a new intestinal specific FXR antagonist for the prevention and treatment of diabetes, which has been packaged for a USA patent; 2) My research demonstrated that repression of adipose hypoxia-inducible factor 1 (HIF1) could be regared as a new target for the treatment of diabetes, which has already been applied for an international patent; 3) I found that hyperhomocysteinemia (HHcy) is an independent risk factor of insulin resistance. To date, I have published 26 SCI papers, which have been cited 191 times by other SCI papers. As the first author, I published 8 SCI papers in the top journals including J Clin Invest., Nat Commun., and Diabetes, etc., with the average impact factor of 8.3, which have already been cited 132 times by other SCI papers. I am in charge of 3 research funds in China. This project aims to uncover the role of ceramide metabolism network in the development of diabetic vascular disease. Mechanistic study of how intestinal FXR regulates ceramide metabolism will contribute to provide a new therapeutic target for the prevention and treatment of diabetic vascular disease. Furthermore, the research will be focused on screening the intestine-specific FXR antagonist, and then evaluating their potential effects for the prevention and treatment of diabetic vascular disease.