BLRD Research Career Scientist Award Application

El-Rifai博士是一名研究职业科学家，自2012年以来一直获得VA优秀奖资助。他是一个成员的 弗吉尼亚州迈阿密的研究和发展委员会，积极指导初级科学家。 他也是副主席和外科教授，肿瘤生物学研究计划的领导者， 迈阿密大学米勒医学院项目开发副主任和西尔维斯特 综合癌症中心。作为西尔维斯特的项目开发副总监，他与 高级领导层创建新的研究计划，包括教师调整，招聘和资源 配置中El-Rifai博士监督研究开发，指导初级教师，并参与研究 培训住院医师和研究员。El-Rifai博士的研究自2012年以来一直由VA优秀奖资助， NCI资助了20年，有197篇同行评审的出版物和220多篇科学摘要。他的研究 旨在更好地了解胃食管癌的生物学，并开发新的治疗方法。 接近。他的实验室在遗传学、表观遗传学和癌症生物学方面提供了独特的培训经验， 专注于胃肠道肿瘤发生的分子机制和新策略的发展 用于癌症治疗。El-Rifai博士培训了超过75名人员，其中包括本科生和 研究生、博士后和住院医生。他指导了超过15名初级教师，其中许多人 他们已经晋升为独立教师职位。El-Rifai博士的实验室与基础 科学和临床研究的同事为了一个共同的目标;更好的临床结果。El-Rifai实验室 利用创新的小鼠模型、3D类器官培养物和人体组织样本。艾尔-瑞法伊博士 在胃癌和食管腺癌领域有重要贡献。他已经成功了 在鉴别胃和食管腺癌中炎症和癌症之间的信号联系中， 发现介导耐药性的新基因，并开发针对上消化道疾病的靶向治疗方法。 胃肠道癌症。El-Rifai博士使用三叶因子1敲除小鼠模型结合体外试验进行研究 和人体组织样品已经显示TFF 1具有有效的抗炎和肿瘤抑制功能， 其在小鼠和人中防止胃癌的发展。艾尔-瑞法伊博士的实验室 对目前理解发展的分子机制做出了重大贡献 食管腺癌（EAC）巴雷特食管是EAC的主要危险因素， 慢性胃食管反流病的后果。他展示了一个表观遗传开关， 几个抗肿瘤的抗氧化反应基因，与其他基因的激活一致，促进肿瘤的发生。 促肿瘤抗氧化反应。他实验室的开创性工作表明，DNA甲基化 几种保护性抗氧化酶的表达，对防止反流诱导的 氧化应激和DNA损伤，从而促进化生性巴雷特食管向EAC的进展。 促肿瘤发生反应包括氧化还原因子1（REF 1，也称为 APE 1）和转录因子NFE 2相关因子2（NRF 2），促进DNA损伤修复，致癌 信号传导和癌细胞存活与制药公司合作，他测试了新的靶向治疗 MLN 8237（alisertib）是一种有效的抗癌药物。MLN 8237现已列入NCI 合作研究和开发协议（CRADA），并在几项临床试验中进行了研究。艾尔医生 Rifai与医学肿瘤学同事合作，已经提出了几个概念，如针对AURKA， mTOR进入临床试验。总之，癌症是一种没有边界的疾病; El-Rifai博士坚信， 建立在强有力的基础科学发现基础上的临床和转化研究是我们赢得这场战斗的途径 对抗癌症

Dr. El-Rifai is a Research Career Scientist funded by a VA merit award since 2012. He is a member of the Research and Development committee at the Miami VA who participates in active mentoring of junior scientists. He is also the vice chair and Professor of Surgery, Leader of the Tumor Biology Research Program, and Associate Director for Program Development at the University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center. As the Associate Director for Program Development at Sylvester, he works with the senior leadership to create new research programs, including faculty alignment, recruitment and resource allocation. Dr. El-Rifai oversees the research development, mentors junior faculty, and participates in research training of residents and fellows. Dr. El-Rifai’s research is funded by VA merit awards since 2012 and continuous NCI funding for 20 years with 197 peer-reviewed publications, and over 220 scientific abstracts. His research aims for a better understanding of the biology of gastro-esophageal cancers and developing novel therapeutic approaches. His laboratory provides unique training experiences in genetics, epigenetics, and cancer biology, focusing on molecular mechanisms of gastrointestinal tumorigenesis and the development of novel strategies for cancer therapeutics. Dr. El-Rifai has trained more than 75 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. Dr. El-Rifai’s laboratory works closely with basic science and clinical research colleagues for one common goal; a better clinical outcome. The El-Rifai laboratory utilizes innovative mouse models, 3D organoid cultures, and human tissue samples. Dr. El-Rifai has made significant contributions in the area of gastric cancer and esophageal adenocarcinoma. 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. Dr. El-Rifai 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 the development of gastric cancer in mouse and human. Dr. El-Rifai lab has made significant contributions to the current understanding of the molecular mechanisms underlying the development of esophageal adenocarcinoma (EAC). Barrett’s esophagus, the main risk factor for EAC, develops as a consequence of chronic gastroesophageal reflux disease. He demonstrated an epigenetic switch that turns off several anti-tumorigenic antioxidant response genes, concordant with activation of other genes that promote a pro-tumorigenic antioxidant response. 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 EAC. The pro-tumorigenic response included constitutive overexpression of redox factor 1 (REF1, also known as APE1) and transcription factor NFE2- related factor 2 (NRF2), promoting DNA damage repair, oncogenic signaling, and cancer cell survival Working with pharmaceutical companies, he tested novel targeted therapy strategies and established MLN8237, alisertib, as a potent anti-cancer drug. MLN8237 is now listed on the NCI Cooperative Research and Development Agreement (CRADA) and is studied in several clinical trials. Dr. El- Rifai, working with medical oncology colleagues, has moved several concepts such as targeting AURKA and mTOR into clinical trials. In summary, cancer is a disease with no boundaries; 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.