代谢重编程是肿瘤的重要特征之一。我们前期发现cMyc、Lin28等在调控肿瘤代谢中的重要作用(Nature 2009; Nature Communs 2014), 但目前尚不清楚这些癌基因的作用是如何被宏观调控的。鉴于染色质的修饰是调控基因表达的重要方式之一，本项目将研究染色质修饰相关蛋白Menin和MBD2是否以及如何调控肿瘤细胞的代谢重编程。我们尚未发表的结果表明，Menin在肿瘤细胞中影响cMyc介导的代谢酶转录。本项目将以此为切入点，深入研究Menin调控肿瘤细胞代谢重编程的分子机制；另一方面，基于我们前期有关MBD2调节干细胞代谢的结果（EMBO J. 2015），我们将深入研究MBD2如何调控肿瘤细胞的代谢重编程及肿瘤的发生发展。本项目的研究目标，是通过解析Menin和MBD2对代谢酶的调控，在染色质修饰的宏观水平上揭示导致肿瘤代谢异常的机制，从而为肿瘤治疗提供新的思路和方法。

A central hallmark of cancer is the deregulated metabolism or metabolic reprogramming that is characterized by aerobic glycolysis, or Warburg Effect. We have documented previously that oncogenes such as cMyc and Lin28 play key roles in facilitating Warburg Effect in cancer cells (Nature 2009; Nature Communs 2014), but it's not clear how the metabolism-regulating roles of those oncogenes are globally regulated. Since chromatin modification is known as an important way to modulate gene expression, we will focus on studying the roles of Menin and MBD2, two chromatin modification-related factors, in regulation of cancer metabolic reprogramming and its underlying mechanisms. Our previous results indicated that MBD2 is involved in stimulating glycolysis in stem cells （EMBO J. 2015）. Meanwhile, Our prelimilary results also indicate that Menin enhances cMyc-mediated transcription. Hence, we will further study the functions and mechanisms of Menin and MBD2 in regulation of cancer metabolism and its impact on cancer development. The goal for this study is to decipher the unappreciated roles for chromatin modifications in cancer metabolic reprogramming.