BLR&D Research Career Scientist Award

BLR

基本信息

批准号：
9898245
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
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9898245
关键词：
17q 20q Acids Africa Animal Model Anti-Inflammatory Agents Antioxidants Area Asia Award Barrett Esophagus Barrett&apos s Tumorigenesis Barrett&apos s carcinogenesis Basic Science Belief Bile fluid Bioinformatics Biological Bone Marrow Transplantation Cancer Biology Cancer Center Cancer Etiology Cellular biology Cessation of life Chronic Clinical Clinical Oncology Clinical Research Clinical Trials Collaborations DARPP DNA Damage DNA Methylation DNA Sequence Alteration Detection of Minimal Residual Disease Development Disease Distal Doctor of Medicine Doctor of Philosophy Drug resistance ERBB2 gene Epidermal Growth Factor Receptor Epigenetic Process Esophageal Adenocarcinoma Esophagus Europe Event Exposure to Faculty Far East Fluorescent in Situ Hybridization Funding Gastric and esophageal adenocarcinomas Gastroenterology Gastroesophageal reflux disease General Population Genes Genetic Goals Health Helicobacter Infections Helicobacter pylori Hematologic Neoplasms Home environment Human Human Resources In Situ Hybridization In Vitro Incidence Individual Inflammation Inflammatory Response Institution International Journals Knockout Mice Laboratories Latin America Link Location Malignant Neoplasms Malignant neoplasm of esophagus Malignant neoplasm of gastrointestinal tract Mediating Mentors Metaphase Metaplasia MicroRNAs Middle East Military Personnel Molecular Molecular Cytogenetics Mus NF-kappa B National Cancer Institute Oncogenes Oncogenic Oncology Operative Surgical Procedures Outcome Oxidative Stress Pathology Patients Peer Review Phase I/II Clinical Trial Positioning Attribute Postdoctoral Fellow Publications Publishing Radiation Oncology Reflux Relapse Research Research Activity Research Personnel Research Training Resistance Risk Risk Factors Role STAT3 gene Sampling Scientist Signal Transduction Soldier Solid Neoplasm Stomach Stomach Carcinoma Surgical Oncology TFF1 gene TP53 gene Testing Therapeutic Time Tissue Sample Training Translational Research 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 genetics carcinogenesis career chemotherapy comparative genomic hybridization epidemiologic data epigenomics experience follow-up functional genomics gastric tumorigenesis gastrointestinal global health glutathione peroxidase graduate student high risk histone methylation human tissue in vitro Assay inhibitor/antagonist interdisciplinary approach interest malignant stomach neoplasm medical schools meetings melanoma member mouse model next generation sequencing novel novel strategies overexpression oxidative DNA damage pre-clinical programs promoter recruit research and development response statistics targeted treatment tool tumor tumorigenesis undergraduate student upper gastrointestinal cancer

项目摘要

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.

项目概要/摘要 El-Rifai 博士在癌症分子研究方面拥有悠久的历史。他建立了强大的胃癌和食道癌研究的国内和国际合作。他的实验室提供癌症研究不同领域的独特培训经验，包括分子机制肿瘤发生和耐药性。 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。实验室拥有一个长期以来对上消化道癌症的功能基因组学和 IntegrOmics（整合组学）感兴趣动物模型、人体样本和体外研究。 El-Rifai 博士领导着一项由 NCI 资助的上消化道癌症研究项目。 El-Rifai 博士有在胃癌、Barrett食管及食管癌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，重点是胃肠道肿瘤发生和癌症治疗新策略的开发。 El-Rifai 博士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 发现和转化研究利用下一代测序、DNA 和组蛋白甲基化，和 miRNA 研究。他已经成功地识别了炎症和炎症之间的信号联系。胃癌和食管腺癌中的癌症，发现介导耐药性的新基因，开发针对上消化道癌症的靶向治疗方法。他的工作使用三叶因子 1 敲除小鼠模型并结合体外测定和人类实验组织样本显示TFF1具有有效的抗炎和抑癌功能，防止小鼠和人类幽门螺杆菌介导的胃癌发展。 El-Rifai 博士实验室有为我们理解发育背后的分子机制做出了重大贡献以及巴雷特癌发生的进展。巴雷特食管是食管癌的主要危险因素腺癌是慢性胃食管反流病的结果，其中远端食道异常暴露于胃酸和胆汁反流。开创性的工作他的实验室表明 DNA 甲基化消除了几种保护性抗氧化剂的表达酶，对于防止反流引起的氧化应激和 DNA 损伤很重要，从而促进化生巴雷特食管进展为食管癌。他的研究旨在了解肿瘤发生的分子基础，以识别和表征调节信号网络中枢的靶标癌发生的重要生物学特征。他的实验室临床前工作发挥了重要作用将极光激酶 A 等一些靶点转移至黑色素瘤和上消化道癌症的 I/II 期临床试验。作为肿瘤外科研究主任，El-Rifai 博士负责监督研究进展，指导初级教师，并参加弗吉尼亚州范德比尔特的住院医师和研究员的研究培训梅哈里医学院。 El-Rifai 博士已培训了 50 多名人员，其中包括本科生和研究生、博士后和住院医师。他指导过超过 15 名初级教员，其中许多他们已晋升为独立教职人员。癌症是一种没有国界的疾病；所以，依赖多学科方法的全球健康倡议对于战胜癌症至关重要。因此，博士。 El-Rifai 的实验室与世界各地的多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研究建立在强大的基础科学发现之上是我们战胜癌症的方法。