PG's and Keratinocyte Adhesion

PG 和角质形成细胞粘附

• 批准号: 8258808
• 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/8258808
• 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; 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; 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; research study; skin lesion; teacher; tissue culture; trafficking; tumor; tumor progression; tumorigenesis; tumorigenic; ultraviolet; ultraviolet irradiation

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 MD 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).

候选人的目标是通过成为一名转化科学家来推进她的学术生涯 由 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。 该候选人是伦敦大学临床医生-研究-教师终身职位的助理教授 罗彻斯特医学院急诊医学系。该候选人毕业于医学专业 1998 年在学校获得了研究杰出的医学博士学位，此后成功地将 基础研究（80%努力）和临床实践（20%努力）的博士后研究。为了接近她 职业目标，候选人在此提出职业发展计划，使她能够获得 通过专门设计用于教育转化科学家的课程进行额外培训，作为 课程由最近授予我们机构的 CTSA NIH 拨款提供。此外，候选人将 继续追求她在皮肤癌生物学领域的成功研究计划以及高级课程 在基础科学领域。为此，候选人发现，在紫外线诱发的皮肤癌中，促进 E-钙粘蛋白（一种介导细胞间接触的粘附分子）的（促癌）下调 角质形成细胞是一个翻译后事件，首先由细胞外 E-钙粘蛋白结构域裂解组成 （主要是 MMP），然后是内吞作用和蛋白水解/溶酶体-蛋白酶体降解。而且， 候选人发现该过程是通过 PGE2 激活 EP2 受体来调节的 紫外线辐射损伤后局部释放。作为 K08 奖项的一部分，候选人将继续学习 关于这个主题，最终将导致确定药物干预的新目标 对抗紫外线诱发的皮肤癌。完成拟议的计划将使候选人能够获得 作为 K08 奖项的一部分，她获得了转化科学硕士学位。由于性质的多样性 拟议的培训，候选人已经招募了一个指导委员会，该委员会提供必要的培训 指导、专业知识和支持。总之，这个 K08 奖项将为候选人的职业生涯做好准备 基础/转化科学，她将能够（1）识别新颖的科学发现及其 实验室动物模型（临床前研究）的潜在临床用途，（2）评估此类 通过临床试验发现并（3）将其应用到临床实践（从实验室到床边到路边）。