Integrin Regulation of Airway Epithelial Proliferation

描述(由申请人提供)：本申请的目标是建立一个独立的研究计划，调查呼吸道上皮细胞增殖的调节机制。通过获得机制洞察力，这项工作的长期目标是确定新的分子靶点，以推进人类呼吸道肿瘤和炎症性疾病的治疗和诊断方法。这位候选人是最近任命的病理学助理教授，目前从事40%的研究和60%的临床/教学工作。他的临床专长是全身和肺部病理学。K02奖的动机是提供工资，以便集中精力进行研究。因此，正如这份申请所建议的那样，候选人的机构努力将被重新分配到75%的研究和25%的临床/教学上。病理学系全力支持这位候选人，并在这一次重新分配。候选人目前占地750平方英尺。英国《金融时报》独立、设备齐全、专注的研究空间。通过与旧金山总医院的肺生物学研究计划和加州大学旧金山分校/Mt.锡安癌症中心的学术环境是职业发展的理想选择。这项研究是最近资助的研究资助申请(HL63993-01)的延伸，旨在阐明整合素αvβ8介导的抑制呼吸道上皮细胞生长的机制。当前提案的目的是使用一种新的生物学相关模型将获得的机械性见解置于生物学背景中。这将通过解决以下三个具体目标的假设来实现：假设：在完整的人类呼吸道中，整合素通过细胞-细胞外-基质相互作用以及通过与生长因子/细胞因子的直接相互作用来调节上皮细胞的动态平衡。具体目的1：建立有效的研究人呼吸道增殖的生物学模型。具体目标2：在生物相关的人类呼吸道模型中，测试整合素在调节上皮细胞生长中的作用。具体目标3：在生物相关的人类呼吸道模型中测试整合素介导的细胞增殖调节机制。

DESCRIPTION (provided by applicant): The goal of this application is to establish an independent research program investigating the mechanisms regulation of airway epithelial proliferation. Through gaining mechanistic insight, the long-term goal of this work is to identify novel molecular targets to advance the therapeutic and diagnostic approaches for neoplastic and inflammatory diseases of the human airway. The candidate is a recently appointed assistant professor of pathology currently engaged in a 40 percent research and 60 percent clinical/teaching effort. His clinical expertise is in general and pulmonary pathology. The impetus for the K02 award is to provide salary to allow for an intensive research focus. Thus, as this application proposes, the candidate's institutional effort would be reallocated to 75 percent research and 25 percent clinical/teaching. The Department of Pathology is in complete support of the candidate and for this time reallocation. The candidate currently occupies 750 sq. ft of independent, fully outfitted, dedicated research space. Through affiliation with the Lung Biology Research Program at San Francisco General Hospital and the UCSF/Mt. Zion Cancer Center, the academic environment is ideal for career advancement. The research proposed is an extension of a recently funded research grant application (HL63993-01), which seeks to elucidate the mechanisms of integrin alpha v beta 8mediated inhibition of airway epithelial cell growth. The purpose of the current proposal is to place the mechanistic insights gained into biologic context using a novel biologically relevant model. This will be accomplished by addressing the following hypothesis in three specific aims: Hypothesis: In intact human airway, integrins mediate epithelial homeostasis through cell-extracellular-matrix interactions and through direct interactions with growth factors/cytokines. Specific Aim 1: To establish a valid biologic model to study human airway proliferation. Specific Aim 2: To test the role of integrins in the regulation epithelial cell growth in a biologically relevant model of the human airway. Specific Aim 3: To test the mechanism of integrin-mediated regulation of cell proliferation in a biologically relevant model of the human airway.