肿瘤、代谢综合征等重大疾病发病机理及药物干预研究一直是分子医学领域的研究热点。申请人长期从事肿瘤代谢研究，在“代谢酶乙酰化修饰”和“代谢参与表观遗传调控”两方面积累了较为丰富的研究经验。前期工作表明，蛋白质乙酰化修饰对于维持代谢酶正常功能至关重要，而代谢酶乙酰化调控异常与肿瘤发生密切相关；代谢基因突变产生致癌代谢物，通过影响表观遗传和基因表达促进肿瘤发生。相关原创性科研成果已发表在Mol Cell，Genes&Development ，Cell Research， EMBO J等权威学术期刊上，并被Mol Cell、EMBO J专文评述。在本次拟申报项目中，申请人将立足前期工作基础，秉持从分子到疾病模型的研究策略，系统研究糖代谢紊乱、表观遗传、基因转录在糖尿病并发症发生发展过程中的变化规律，全面解析高血糖“代谢记忆”分子机制，旨在为指导糖尿病并发症预防性治疗药物研发提供新的思路。

Cancer and metabolic syndrome and their targeting drug intervention have become hot topics in the field of molecular medicine. The applicant has long been studying tumor metabolism, and has extensive experience in the research fields of ‘acetylation regulation of metabolic enzymes’ and ‘epigenetic control by metabolites’. The applicant and her co-workers have previously shown that acetylation plays an important role in regulating the normal activity/function of metabolic enzymes, and that the dysregulation of metabolic enzymes by acetylation plays a vital role in tumor development. Moreover, mutations in metabolic genes lead to the pathological accumulation of oncometabolites, which can alter the epigenetic landscape, regulate gene expression, and eventually contribute to tumorigenesis. These findings have been published in academic journals with high impact factors, such as Mol Cell, Genes&Development, Cell Research, EMBO J, ect, and some works have been previewed and highlighted by Mol Cell and EMBO J. In the current proposed project, the applicant will be based on previous studies in tumor metabolism and expand to investigate the association among glucose metabolism dysregulation, epigenetic alterations, and gene regulation during the development of diabetes complications at both cellular and animal levels. This study will gain mechanistic insight into the molecular mechanism of hyperglycemia "metabolic memory" and provide new ideas to drug design development and therapy for prophylactic treatment of diabetes complications.