PG's and Keratinocyte Adhesion

PG 和角质形成细胞粘附

• 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
• 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

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K 08临床医生-科学家发展奖支持的额外基础研究和教学培训，成为一名翻译科学家，从而促进她的学术生涯。候选人是罗切斯特大学医学院急诊医学系临床研究教师终身教职的助理教授。候选人于1998年从医学院毕业，获得医学博士学位。自成立以来，他成功地将基础研究（80%的努力）与临床实践（20%的努力）结合起来。为了实现她的职业目标，候选人在这里提出了一个职业发展计划，这将使她能够通过专门设计的课程来获得额外的培训，以教育翻译科学家，作为最近授予CTSA NIH授予我们机构的课程的一部分。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UV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-细胞接触的粘附分子）的促进性（促癌）下调是一种翻译后事件，首先由细胞外E-钙粘蛋白结构域裂解（主要由MMP）组成，然后是内吞作用和蛋白水解/溶酶体-蛋白酶体降解。此外，候选人已经发现，这一过程是由紫外线辐射损伤后局部释放的PGE 2激活EP 2受体调节的。作为K 08奖项的一部分，候选人将继续她对这一主题的研究，这最终将导致对紫外线诱导的皮肤癌的药理学干预的新靶点的确定。完成拟议的计划将使候选人获得翻译科学硕士学位作为她的K 08奖的一部分。由于拟议培训的多样性，候选人聘请了一个辅导委员会，提供必要的辅导、专门知识和支持。总之，这个K 08奖将为候选人在基础/转化科学的职业生涯做好准备，因此她将能够（1）在实验室的动物模型（临床前研究）中识别新的科学发现及其潜在的临床实用性，（2）通过临床试验评估这些发现，以及（3）将其用于临床实践（从实验室到床边到路边）。