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BLR&D Research Career Scientist Award

BLR

基本信息

批准号：
9343273
负责人：
WAEL EL-RIFAI
金额：
--
依托单位：
VETERANS HEALTH ADMINISTRATION
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/9343273
关键词：
17q 20q Acids Africa Animal Model Anti-Inflammatory Agents Anti-inflammatory Antioxidants Area Asia Award Barrett Esophagus 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 Esophageal Adenocarcinoma Esophagus Europe Event Faculty Far East Fluorescent in Situ Hybridization Funding Gastric Adenocarcinoma Gastroenterology Gastroesophageal reflux disease Gene Targeting General Population Genes Genetic Goals Health Helicobacter Infections Helicobacter pylori Hematologic Neoplasms Home environment Human Human Resources 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 Metaplastic MicroRNAs Middle East Military Personnel Molecular Molecular Cytogenetics Mus NF-kappa B National Cancer Institute Oncogenes Oncogenic Operative Surgical Procedures Outcome Oxidative Stress Pathology Patients Peer Review Phase Positioning Attribute Postdoctoral Fellow Publications Publishing Radiation Oncology Recruitment Activity Reflux Relapse Research Research Activity Research Personnel Research Training Resistance Risk Risk Factors Role STAT3 gene STK6 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 Proteins United States National Academy of Sciences Universities Veterans Work World Health Organization anticancer research antioxidant enzyme aurora-A kinase beta catenin cancer genetics carcinogenesis career chemotherapy comparative genomic hybridization epidemiologic data epigenomics experience follow-up functional genomics 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 oncology overexpression oxidative DNA damage pre-clinical programs promoter research and development response statistics targeted treatment tool tumor tumorigenesis undergraduate student upper GI series

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.

项目总结/摘要博士El-Rifai在癌症分子研究方面有着悠久的历史。他建立了强大的国家和国际合作研究胃癌和食管癌。他的实验室在癌症研究的不同领域提供独特的培训经验，包括分子机制肿瘤发生和抗药性的关系。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）和临床部门（病理学、肿瘤学、放射学肿瘤学、外科学、胃肠病学）的共同目标;更好的临床结果。实验室有一个长期以来对上消化道癌症的功能基因组学和整合组学（整合组学）的兴趣，动物模型、人体样本和体外研究。 El-Rifai博士领导了一个由NCI资助的上消化道癌症研究项目。艾尔-瑞法伊博士在胃癌、Barrett食管和食管癌等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，胃肠道肿瘤发生和癌症治疗新策略的发展。El-Rifai博士研究包括将动物模型作为鉴定肿瘤发展和进展的工具。艾尔医生 Rifai发现和转化研究利用下一代测序，DNA和组蛋白甲基化， miRNAs研究他已经成功地确定了炎症和炎症之间的信号联系，胃癌和食管腺癌，发现新的基因介导耐药性，并开发针对上消化道癌症的靶向治疗方法。他的工作是使用三叶因子1敲除小鼠模型结合体外试验和人类组织样本显示TFF 1具有有效的抗炎和肿瘤抑制功能，保护H。幽门介导的小鼠和人胃癌的发展。艾尔-瑞法伊博士的实验室为我们理解发展的分子机制做出了重大贡献以及巴雷特癌的发展Barrett食管，食管癌的主要危险因素腺癌，发展为慢性胃食管反流病的结果，其中远端食道变得异常地暴露于酸和胆汁从胃反流。的开创性工作他实验室的一项研究表明，DNA甲基化消除了几种保护性抗氧化剂的表达，酶，对于防止反流诱导的氧化应激和DNA损伤很重要，从而促进化生性Barrett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枢纽的靶点，致癌作用的重要生物学特征。他的实验室临床前工作有助于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期临床试验中。作为外科肿瘤学研究的主任，El-Rifai博士监督研究的发展，指导初级教师，并参加范德比尔特，弗吉尼亚州的居民和研究员的研究培训，梅哈里医学院。El-Rifai博士培训了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。癌症是一种没有边界的疾病，因此，依靠多学科方法的全球卫生倡议对于战胜癌症至关重要。因此，博士。 El-Rifai的实验室与全球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坚实的基础科学发现上的方法是赢得我们与癌症的斗争的方法。