PG's and Keratinocyte Adhesion

描述(由申请者提供)：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，通过成为一名翻译科学家来推进她的学术生涯。应聘者是罗切斯特大学医学院急诊医学系临床医生-研究-教师终身教职的助理教授。这位候选人1998年从医学院毕业，获得了杰出的研究医学博士学位，此后成功地将基础研究的博士后研究(80%的努力)与临床实践(20%的努力)结合在一起。为了达到她的职业目标，应聘者在这里提出了一项职业发展计划，使她能够通过专门为教育翻译科学家而设计的课程工作获得额外的培训，这是最近授予我们研究所的CTSA NIH赠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，以及基础科学方面的高级课程。为此，候选人发现，在紫外线诱导的皮肤癌中，促进(致癌)下调的E-钙粘蛋白是一种介导角质形成细胞之间细胞-细胞接触的黏附分子，是一种翻译后事件，首先是细胞外E-钙粘素结构域的裂解(主要由MMPs)，然后是内吞作用和蛋白降解/溶酶体-蛋白酶体降解。此外，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，候选人将继续她对这一主题的研究，这最终将导致确定针对紫外线诱发皮肤癌的药物干预的新靶点。计划的完成将使候选人能够获得翻译科学硕士学位，这是她K08奖项的一部分。由于拟议培训的性质多种多样，候选人已招募了一个指导委员会，提供必要的指导、专业知识和支持。总之，K08奖将为候选人在基础/翻译科学领域的职业生涯做好准备，她将能够(1)在实验室中识别新的科学发现及其在动物模型(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)将其应用于临床实践(从床到床到现场)。

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).