The exploration of linking RNF20 depended histone H2B ubiquitylation and tumor suppressor gene p53 expression with inflammation and inflammation associated cancer

在我在以色列Rehobel Weizmann研究所分子细胞生物学系Moshe Oren教授实验室的短期研究中，我将加入一个将连接酶RNF 20依赖的组蛋白H2 B（H2 Bub 1）泛素化与结直肠癌发生中的炎症和炎症相关过程联系起来的项目。通过使用敲除小鼠模型RNF 20 +/-以及p53测序，我将参与进一步检查炎症微环境以及RNF 20耗尽与肿瘤抑制基因p53的表达和突变状态的可能联系。为了检查这些来自小鼠模型和细胞培养物的结果对于人类患者结肠炎和结直肠癌的重要性，我将通过建立H2 Bub 1免疫组织化学方案并使用来自患者样品的肿瘤来源RNA的qRT-PCR来检查人类结直肠组织中p53表达和突变状态、H2 Bub 1和细胞因子水平如白介素6和白介素8的相关性。我的主要目标是学习新的实验室技能，在一个领域的主题接近我的博士论文在一个著名的和装备精良的实验室，如奥伦实验室。通过学习上述实验室技能并参与该小组的全外显子组测序，我将能够扩展我目前在血浆中自由漂浮肿瘤DNA检测领域的研究项目，并找到连接不同肿瘤实体和炎症过程的突变。

In my short term fellowship at the laboratory of Professor Moshe Oren at the Department of Molecular Cell Biology of the Weizmann Institute in Rehovot, Israel, I will join a project linking the ligase RNF20 dependent ubiquitylation of histone H2B (H2Bub1) to inflammation and inflammation associated processes in colorectal cancerogenesis. By working with the knock out mouse model RNF20 +/- as well as p53 sequencing I will participate in the further examination of the inflammatory microenvironment and possible linkage of RNF20 depletion with the expression and mutation status of tumor suppressor gene p53. In order to examine the importance of these from mouse model and cell cultures derived findings for colitis and colorectal cancer in human patients I will examine the correlation of p53 expression and mutation status, H2Bub1 and cytokine levels like interleukine 6 and 8 in human colorectal tissue by establishing a H2Bub1 immunhistochemistry protocol and using qRT-PCR from tumor derived RNA of patient samples. My main goal is to learn new lab skills in a field thematically close to my doctoral thesis in a known and well-equipped laboratory such as the Oren lab. By learning these above mentioned lab skills and participating in the group´s performance of whole exome sequencing I will be able to expand my current research projects in the field of free floating tumor DNA detection in plasma and finding mutations that link different tumor entities and inflammatory processes.