PG's and Keratinocyte Adhesion

PG 和角质形成细胞粘附

基本信息

批准号：
7686824
负责人：
Sabine M Brouxhon
金额：
$ 13.11万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-12 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7686824
关键词：
Acute Address Adhesions Adhesives Agonist Animal Model Award Awareness Basic Science Cadherin Domain Cancer Biology Cancer Etiology Cell Adhesion Molecules Cell surface Cells Chronic Clinical Clinical Trials Coupled Cytokeratin Cytoplasm Deformity Development Development Plans Dinoprostone Doctor of Medicine Dose Down-Regulation E-Cadherin Educational Curriculum Emergency Medicine Endocytosis Epithelial Epithelial Cells Event Exposure to Genetic Goals Grant Healthcare Human In Vitro Inbred HRS Mice Incidence Injury Institution Intervention Invaded Kinetics Knockout Mice Laboratories Lead Loss of E-cadherin Expression Lysosomes Malignant - descriptor Malignant Neoplasms Matrix Metalloproteinases Measures Mediating Medical Membrane Glycoproteins Mentorship Messenger RNA Modeling Morbidity - disease rate Mus Nature Oncogenic Pathway interactions Phenotype Process Proliferating Proteins Radiation Injuries Receptor Signaling Recruitment Activity Research Research Personnel Role Route Scientist Skin Cancer Skin Neoplasms Squamous cell carcinoma Stimulus Testing Time Training Training Support Transgenic Mice Translational Research Tumor Cell Line UV induced Ubiquitination Ultraviolet Rays United States National Institutes of Health Universities base bench to bedside butaprost career career development clinical practice cost cyclooxygenase 2 design extracellular human tissue inhibitor/antagonist keratinocyte medical schools mortality mouse model multicatalytic endopeptidase complex neoplastic novel preclinical study professor programs prostaglandin EP2 receptor receptor research study skin lesion teacher tissue culture trafficking tumor tumor progression tumorigenesis tumorigenic ultraviolet ultraviolet irradiation

项目摘要

DESCRIPTION (provided by applicant): The candidate's goal is to advance her academic career by becoming a translational scientist through additional basic research and didactic training supported by a K08 Clinician-Scientist Development Award. The candidate is an Assistant Professor in the Clinician-Research-Teacher tenure-track at the University of Rochester School of Medicine, Department of Emergency Medicine. The candidate graduated from medical school in 1998 receiving an M.D. with Distinctions in Research, and since has successfully combined postdoctoral studies in basic research (80% effort) with clinical practice (20% effort). To reach her professional goal, the candidate proposes here a career development plan that will enable her to obtain additional training through coursework specifically designed to educate translational scientists as part of the curriculum available by the recently awarded CTSA NIH grant to our Institution. Moreover, the candidate will continue to pursue her successful research plan in skin cancer biology, coupled with advanced level courses in basic sciences. To this end, the candidate has discovered that in UV-induced skin cancers, the facilitative (pro-oncogenic) down-regulation of E-cadherin, an adhesion molecule mediating cell-cell contacts between keratinocytes, is a post-translational event consisting first of extracellular E-cadherin domain cleavage (primarily by MMPs), followed by endocytosis and proteolytic/ lysosomal-proteasomal degradation. Moreover, the candidate has discovered that this process is regulated by activation of the EP2 receptor by PGE2 released locally after UV radiation injury. As part of this K08 award, the candidate will continue her studies on this topic, which ultimately will lead to the identification of new targets for pharmacological intervention against UV-induced skin cancers. Completion of the proposed plan will enable the candidate to receive a Master's in Translational Science degree as part of her K08 award. Due to the diverse nature of the proposed training, the candidate has recruited a mentorial committee that provides the necessary mentorship, expertise and support. In conclusion, this K08 award will prepare the candidate for a career in basic/translational science, whereby she will be able to (1) identify novel scientific discoveries and their potential clinical usefulness in animal models (preclinical studies) in the laboratory, (2) evaluate such discoveries through clinical trials, and (3) bring their use to clinical practice (bench-to-bedside-to-curb).

描述（由申请人提供）：候选人的目标是通过 K08 临床医生-科学家发展奖支持的额外基础研究和教学培训，成为一名转化科学家，从而推进她的学术生涯。该候选人是罗彻斯特大学医学院急诊医学系的临床医生-研究-教师终身教授助理教授。该候选人于 1998 年从医学院毕业，获得研究杰出医学博士学位，此后成功地将基础研究（80% 努力）的博士后研究与临床实践（20% 努力）结合起来。为了实现她的职业目标，候选人在此提出了一个职业发展计划，该计划将使她能够通过专门为教育转化科学家而设计的课程获得额外的培训，作为最近授予我们机构的 CTSA NIH 拨款提供的课程的一部分。此外，候选人将继续追求她在皮肤癌生物学方面的成功研究计划，以及基础科学的高级课程。为此，候选人发现，在紫外线诱导的皮肤癌中，E-钙粘蛋白（一种介导角质形成细胞之间细胞间接触的粘附分子）的促进（促癌）下调是一个翻译后事件，首先包括细胞外 E-钙粘蛋白结构域裂解（主要通过 MMP），然后是胞吞作用和蛋白水解/溶酶体-蛋白酶体降解。此外，该候选人还发现，这一过程是通过紫外线辐射损伤后局部释放的 PGE2 激活 EP2 受体来调节的。作为 K08 奖项的一部分，候选人将继续对该主题的研究，最终将确定针对紫外线诱发的皮肤癌的药物干预的新靶标。完成拟议计划将使候选人获得转化科学硕士学位，作为其 K08 奖项的一部分。由于拟议培训的多样性，候选人已招募了一个指导委员会来提供必要的指导、专业知识和支持。总之，该 K08 奖项将为候选人在基础/转化科学领域的职业生涯做好准备，她将能够 (1) 识别新颖的科学发现及其在实验室动物模型（临床前研究）中的潜在临床用途，(2 ）通过临床试验评估这些发现，以及（3）将其应用到临床实践（从实验室到床边到路边）。