TRANSCRIPTIONAL REGULATION OF THE B1AR BY C-MYC

描述(由申请人提供)： Cobre计划的科学目标是通过定义其中几个事件如何影响胎儿和新生儿的发育，增加我们对心肺发育的了解，并帮助开发新的治疗干预策略。我们将研究：1)细胞周期控制蛋白p57Kip2的调节及其在心肌生长和分化中的作用；2)β1肾上腺素能受体(β1AR)的表达及其在从增殖期、胚胎期到出生后生命过渡过程中的作用；3)机械拉伸对胚胎晚期/胎肺发育影响的信号转导途径；4)呼吸上皮中Fas/FasL的时空调控及其在肺发育和肺重塑中的作用；5)原癌基因c-myc在调控β1AR基因表达中的作用；5)IL-10基因和STAT-6信号通路中断对生殖的病理生理影响。 Cobre的计划目标是在促进科学方法的创造力和跨学科合作的跨学科环境中为初级教师提供科学和职业指导。我们最近完成了一座新的、最先进的研究设施的建设。它容纳了成功的高级调查人员以及这群年轻的科学家，他们都表现出了独立职业的极大潜力。这一奖项将使我们能够将这一新设施与所需的外部支持结合起来，使这些研究人员能够与各自领域的领先科学家合作，并利用当代细胞和分子生物学的辅助手段来解决中晚期妊娠胎儿发育中的重要问题。在强有力的调查和探索环境中提供支持性环境，将使我们能够加强/确保他们作为独立调查人员的职业轨迹。这些区域的临床相关性被证明是因为它们很有可能识别调节胎儿生长和主要器官系统的生长和分化的重要机制。这些领域反映在参与该生物研究卓越中心(COBRE)的围产期生物学研究人员的特殊研究专业知识中。该项目将设在罗德岛州的妇幼医院。它将为初级学院的四个完整项目和两个试点项目提供支持，这些项目将由知名调查人员指导。来自其他中心的一批杰出的研究人员将作为外部科学咨询委员会提供支持和合作。

DESCRIPTION (provided by applicant): The scientific aims of this COBRE Program are to increase our understanding of cardiopulmonary development and help to develop strategies for new therapeutic interventions by defining how several of these events impact fetal and newborn development. We will examine: 1) The regulation of the cell cycle control protein p57Kip2 and its role in myocardial growth and differentiation; 2) The expression of the beta-1 adrenergic receptor (beta1AR) and its role in cardiac growth during the transition from the proliferative, embryonic period to postnatal life; 3) The signal transduction pathways mediating the effects of mechanical stretch on late embryonic/fetal lung development; 4) The spatio-temporal regulation of Fas/FasL in the respiratory epithelium and role in lung development and lung remodeling; 5) The role of the protooncogene c-myc in the regulation of the beta1AR gene expression; 5) the pathophysiological effects of disruption of the IL-10 gene and the STAT 6 signaling pathway on reproduction. The programmatic aims of this COBRE are to provide scientific and career mentorship to Junior Faculty in an interdisciplinary environment that fosters creativity and transdisciplinary collaboration in scientific approaches. We have recently completed construction of a new, state-of-the-art research facility. It houses successful, senior investigators as well as this group of young scientists, all of whom have demonstrated excellent potential for independent careers. This award will allow us to couple this new facility with the extramural support needed to allow these investigators to collaborate with leading scientists in their fields and to utilize contemporary appraches in cell and molecular biology to address important issues in the development of the mid-late gestation fetus. The combination of a supportive environment within a robust setting of inquiry and exploration will allow us to enhance/ensure their career trajectories as independent investigators. The clinical relevance of these areas is borne out by their high likelihood to identify important mechanisms for the regulation of fetal growth and the growth and differentiation of major organ systems. These areas are reflected in the special research expertise of the investigators participating in this Center Of Biological Research Excellence (COBRE) for Perinatal Biology. This project will be based at the Women and Infants' Hospital of Rhode Island. It will provide support for four full projects and 2 pilot projects of Junior Faculty who will me mentored by established investigators. An outstanding group of investigators from other centers will provide support and collaboration as the External Scientific Advisory Committee.