BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

• 批准号: 10480519
• 负责人: WAEL EL-RIFAI
• 金额: --
• 依托单位: MIAMI VA HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2029-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10480519
• 关键词: 20q; 3-Dimensional; Animal Model; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Area; Award; Barrett Esophagus; Barrett' s Tumorigenesis; Basic Science; Belief; Binding; Bioinformatics; Biological; Biology; Cancer Biology; Cancer Etiology; Cell Survival; Cellular biology; Cessation of life; Chronic; Clinical; Clinical Oncology; Clinical Research; Clinical Trials; Communication; Complex; Comprehensive Cancer Center; Cooperative Research and Development Agreement; DNA Damage; DNA Methylation; DNA Repair; DNA Sequence Alteration; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Drug resistance; Epigenetic Process; Esophageal Adenocarcinoma; FRAP1 gene; Faculty; Far East; Finland; Fluorescent in Situ Hybridization; Funding; Gastric and esophageal adenocarcinomas; Gastroenterology; Gastroesophageal reflux disease; General Population; Genes; Genetic; Genetic Transcription; Goals; Health; Helicobacter Infections; Helicobacter pylori; Home; Human; Human Resources; Incidence; Individual; Infection; Inflammation; International; Journals; Knockout Mice; Laboratories; Leadership; Link; Location; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of gastrointestinal tract; Mediating; Medical Oncology; Mentors; Metaphase; Metaplasia; Methylation; MicroRNAs; Middle East; Military Personnel; Modeling; Molecular; Molecular Cytogenetics; Mus; NF-kappa B; National Cancer Institute; Nature; Oncogenes; Oncogenic; Oncology; Operative Surgical Procedures; Organoids; Outcome; Oxidation-Reduction; Oxidative Stress; Pathology; Peer Review; Peptides; Pharmacologic Substance; Play; Positioning Attribute; Postdoctoral Fellow; Program Development; Publications; Publishing; Radiation Oncology; Reflux; Research; Research Activity; Research Training; Resource Allocation; Risk; Risk Factors; Role; STAT3 gene; Sampling; Scientist; Signal Transduction; Soldier; Solid Neoplasm; Stomach Carcinoma; TFF1 gene; TP53 gene; Testing; Therapeutic; Tissue Sample; Training; Translational Research; Translations; Tumor Biology; Tumor Necrosis Factor Receptor; Tumor Suppression; Tumor Suppressor Genes; Tumor Suppressor Proteins; United States National Academy of Sciences; Universities; Veterans; Work; World Health Organization; anticancer research; antioxidant enzyme; aurora kinase A; beta catenin; cancer cell; cancer genetics; carcinogenesis; career; clinical investigation; comparative genomic hybridization; epidemiologic data; epigenomics; experience; functional genomics; gastric tumorigenesis; gastroesophageal cancer; gastrointestinal; graduate student; high risk; histone methylation; human tissue; in vitro Assay; indexing; innovation; interest; malignant stomach neoplasm; medical schools; meetings; member; military veteran; mouse model; new therapeutic target; next generation sequencing; novel; novel strategies; novel therapeutic intervention; overexpression; professor; programs; recruit; research and development; response; serial analysis of gene expression; statistics; targeted treatment; transcription factor; transcriptome sequencing; tumorigenesis; tumorigenic; undergraduate student; upper gastrointestinal cancer

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.

El-Rifai博士是一名研究职业科学家，自2012年以来获得VA优异奖。 迈阿密弗吉尼亚州的研发委员会参加了初级科学家的积极心理。 他还是外科副主席兼教授，肿瘤生物学研究计划的负责人， 迈阿密米勒大学医学院和西尔维斯特大学计划开发副主任 综合癌症中心。作为西尔维斯特计划开发副主任，他与 高级领导者创建新的研究计划，包括教师的一致性，招聘和资源 分配。 El-Rifai博士负责研究开发，指导初级教师，并参与研究 培训居民和研究员。 El-Rifai博士的研究是自2012年以来由VA Merit Awards资助的，并继续 NCI为20年的NCI资金提供了197个同行评审的出版物，超过220个科学摘要。他的研究 旨在更好地了解胃食管癌的生物学并开发新的疗法 方法。他的实验室在遗传学，表观遗传学和癌症生物学方面提供独特的培训经验， 专注于胃肠道肿瘤发生的分子机制和新型策略的发展 用于癌症治疗。 El-Rifai博士已经培训了75多名人员，包括本科生和 研究生，博士后和居民。他被指导了15多名初级教职员工，许多 他们晋升为独立教师职位。 El-Rifai博士的实验室与Basic紧密合作 一个共同目标的科学与临床研究合作；更好的临床结果。 El-Rifai实验室 利用创新的小鼠模型，3D器官培养物和人体组织样品。 El-Rifai博士做了 胃癌和食管腺癌区域的重要贡献。他已经成功了 在确定胃和食管腺癌中炎症与癌症之间的信号传导联系时， 发现介导耐药性的新型基因，并开发了针对上部的靶向治疗方法 GI癌。 El-Rifai博士使用Trefoil系数1基因敲除小鼠模型与体外测定 人体组织样品表明TFF1具有潜在的抗炎和肿瘤抑制功能， 可以防止小鼠和人类胃癌的发展。 El-Rifai Lab博士已经制作了 对开发基础的分子机制的当前理解的重要贡献 食管腺癌（EAC）的。 Barrett的食管是EAC的主要危险因素，它发展为 慢性胃食管反射疾病的结果。他展示了一个表观遗传开关 几种抗肿瘤抗氧化剂反应基因，与促进A的其他基因的激活一致 促肿瘤抗氧化剂反应。他实验室的开创性工作表明DNA甲基化电线 消除几种受保护的抗氧化剂酶的表达，对于防止反射诱导的 氧化应激和DNA损伤，从而支持化生Barrett食管向EAC的进展。 促氧化物的反应包括氧化还原因子1的本构过表达（Ref1，也称为 APE1）和转录因子NFE2-相关因子2（NRF2），促进DNA损伤修复，致癌 信号传导和与制药公司合作的癌细胞生存，他测试了新的靶向治疗 策略并建立了MLN8237，Alisertib，作为一种潜在的抗癌药物。现在在NCI上列出了MLN8237 合作研究与发展协议（CRADA），并在几项临床试验中进行了研究。 El-博士 与医学肿瘤学同事合作的Rifai已提出了一些概念，例如针对Aurka和 MTOR进入临床试验。总而言之，癌症是一种无边界的疾病。 El-Rifai博士公司相信 基于强大的基础科学发现建立的临床和翻译研究是赢得我们的战斗的方式 反对癌症。