BLR&D Research Career Scientist Award

项目摘要/摘要 埃尔-里法伊博士在癌症的分子研究方面有着长期的记录。他已经建立了强大的 胃癌和食道癌研究的国内和国际合作。他的实验室 在癌症研究的不同领域提供独特的培训经验，包括分子机制 肿瘤的发生和耐药性。El-Rifai博士的实验室与基础科学(细胞生物学、 癌症生物学、统计学、生物信息学)和临床科室(病理学、肿瘤学、放射学 肿瘤学、外科、胃肠病学)为了一个共同的目标；更好的临床结果。这个实验室有一个 对上消化道癌症的功能基因组学和整合组学(整合组学)的长期兴趣 动物模型、人体样本和体外研究。 El-Rifai博士领导着一个由NCI资助的具有竞争力的上消化道癌症研究项目。El-Rifai博士已经 在胃癌、Barrett‘s食道和食道领域做出了重大贡献 腺癌。他的主要研究兴趣是遗传学、表观遗传学和癌症生物学，重点是 胃肠道肿瘤的发生和癌症治疗新策略的发展。埃尔-里法伊医生的 研究包括将动物模型作为识别肿瘤发展和进展的工具。艾尔博士- Rifai的发现和翻译研究利用了下一代测序、DNA和组蛋白甲基化， 和miRNAs研究。他已经成功地确定了炎症和炎症之间的信号联系 胃腺癌和食道腺癌中的癌症，发现介导耐药性的新基因， 以及开发针对上消化道癌症的靶向治疗方法。 他的工作使用了三叶因子1基因敲除小鼠模型，并结合了体外测试和人类 组织样本显示，TFF1具有强大的抗炎和肿瘤抑制作用， 对幽门螺杆菌介导的小鼠和人胃癌的保护作用。埃尔-里法伊博士的实验室已经 为我们理解发育的分子机制做出了重大贡献 和巴雷特癌变的进展。Barrett‘s食道，食管炎的主要危险因素 腺癌，发展为慢性胃食道反流病的结果，在远端 食道会异常地暴露在胃酸和胆汁回流中。开创性的工作 他的实验室发现，DNA甲基化可以消除几种保护性抗氧化剂的表达。 酶，对于防止回流引起的氧化应激和DNA损伤非常重要，从而促进 化生性Barrett‘s食道癌的进展。他的研究旨在理解 肿瘤发生的分子基础，以识别和表征调控信号网络枢纽和 致癌的重要生物学特征。他的实验室临床前工作对 将一些靶点，如极光激酶A，转移到黑色素瘤和上消化道癌症的I/II期临床试验。 作为外科肿瘤学研究部的主任，El-Rifai博士负责监督研究进展， 指导初级教员，并参与弗吉尼亚州范德比尔特的住院医生和研究员的研究培训 梅哈里医学院。El-Rifai博士已经培训了50多名人员，其中包括本科生和 研究生、博士后和住院医生。他已经指导了15名初级教职员工，其中许多人 他们已经晋升为独立的教职员工。癌症是一种没有国界的疾病；因此， 依赖多学科方法的全球卫生倡议对于战胜癌症至关重要。正因为如此，Dr。 El-Rifai的实验室与世界各地的几个学术机构和癌症中心合作 欧洲、非洲、亚洲和拉丁美洲。El-Rifai博士坚信临床和转化性研究 建立在强大的基础科学发现基础上的是我们战胜癌症的途径。

Project Summary/Abstract Dr. El-Rifai has a long standing track record in the molecular studies of cancer. He has established strong national and international collaborations for the studies of gastric and esophageal cancer. His laboratory provides unique training experiences in diverse areas of cancer research that include molecular mechanisms of tumorigenesis and drug resistance. Dr. El-Rifai's laboratory works closely with basic science (Cell biology, Cancer Biology, Statistics, Bioinformatics) and clinical Departments (Pathology, Oncology, Radiation Oncology, Surgery, Gastroenterology) for one common goal; a better clinical outcome. The laboratory has a long-standing interest in functional genomics and IntegrOmics (integrated omics) in upper GI cancers using animal models, human samples, and in vitro studies. Dr. El-Rifai leads a competitively NCI-funded research program in upper GI cancers. Dr. El-Rifai has made significant contributions in the area of gastric cancer, Barrett's esophagus and esophageal adenocarcinoma. His major research interests are in genetics, epigenetics, and cancer biology, focusing on gastrointestinal tumorigenesis and the development of novel strategies for cancer therapeutics. Dr. El-Rifai's research encompasses animal models as tools for identification of tumor development and progression. Dr. El- Rifai discovery and translational research utilize next generation sequencing, DNA and histone methylation, and miRNAs studies. He has been successful in identifying the signaling links between inflammation and cancer in gastric and esophageal adenocarcinomas, discovering novel genes that mediate drug resistance, and developing targeted therapy approaches for upper GI cancers. His work using the trefoil factor 1 knockout mouse model in conjunction with in vitro assays and human tissues samples has shown that TFF1 has potent anti-inflammatory and tumor suppressor functions, which protect against H. pylori-mediated development of gastric cancer in mouse and human. Dr. El-Rifai lab has made significant contributions to our understanding of the molecular mechanisms underlying the development and progression in Barrett's carcinogenesis. Barrett's esophagus, the main risk factor for esophageal adenocarcinoma, develops as a consequence of chronic gastroesophageal reflux disease where the distal esophagus becomes abnormally exposed to acid and bile refluxate from the stomach. The pioneering work from his lab has shown that DNA methylation wipes out the expression of several protective antioxidant enzymes, important for protecting against reflux-induced oxidative stress and DNA damage, thereby facilitating progression of metaplastic Barrett's esophagus to esophageal cancer. His studies aim to understand the molecular basis of tumorigenesis to identify and characterize targets that regulate signaling network hubs and important biological features of carcinogenesis. His laboratory pre-clinical work has been instrumental in moving some targets such as Aurora kinase A to phase I/II clinical trials in melanoma and upper GI cancers. As the director of Surgical Oncology Research, Dr. El-Rifai oversees the research development, mentors junior faculty, and participates in research training of residents and fellows in Vanderbilt, VA, and Meharry Medical College. Dr. El-Rifai has trained more than 50 personnel that included undergraduate and graduate students, postdocs, and residents. He has mentored more than 15 junior faculty members, many of whom have progressed to independent faculty positions. Cancer is a disease with no boundaries; therefore, Global Health initiatives that rely on multi-disciplinary approaches are crucial for defeating cancer. As such, Dr. El-Rifai's laboratory collaborates with several academic institutions and cancer centers worldwide that span Europe, Africa, Asia, and Latin America. Dr. El-Rifai has a firm belief that clinical and translational research founded on strong basic science discoveries is the way to win our battle against cancer.