Regulation of Fibroblast Survival in the Collagen Matrix

胶原基质中成纤维细胞存活的调节

• 批准号: 6382569
• 负责人: MARK A CARLSON
• 金额: $ 10.62万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-30 至 2006-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6382569
• 关键词: actins; apoptosis; biological signal transduction; cell growth regulation; collagen; cysteine endopeptidases; enzyme activity; extracellular matrix; fibroblasts; focal adhesion kinase; human tissue; immunocytochemistry; integrins; intermolecular interaction; laboratory mouse; p53 gene /protein; phosphatidylinositol 3 kinase; phosphorylation; protein structure function; skin; terminal nick end labeling; transcription factor; western blottings; wound healing

DESCRIPTION (provided by applicant): The candidate is pursuing a career in academic surgery as an Assistant Professor of Surgery at the University of Nebraska Medical Center. His clinical interests include minimally invasive and robotic surgery and surgery of the abdominal wall His basic science interests include the regulation of wound healing, granulation tissue regression, and tissue regeneration. He has completed a 6 year residency in general surgery (Medical College of Wisconsin), a 1 year fellowship in minimally invasive surgery (MCW), and a 3 year fellowship in basic research (wound healing) with Fred Giinnell at the University of Texas Southwestern Medical Center. His short-term goal is to establish, with the help of extramural funding, a career in academic surgery at UNMC. His long-term goals include a greater understanding of the healing mechanism, progress towards achieving tissue regeneration, and advancement of minimally invasive and robotic surgery. The UNMC Surgery Chairman hired the candidate with the intent that the candidate would concentrate 75 percent of his efforts on research and career development. The candidate?s career development plan involves a combination of basic science research, didactic lectures, seminars, specialty courses, scientific meetings, research presentations, and scholarly debate/discussions. The candidate has 3 sponsors: a senior academic surgeon, a surgeon who is an established wound healing investigator, and a cell biologist experienced in apoptotic signal transduction. The latter two sponsors have NIH-funded laboratories. The candidate foresees a 4 year period to perform the proposed experiments and prepare an R01 application. The candidate's research plan will investigate the regulation of fibroblast survival in the collagen matrix. The clinical relevance is that since the fibroblast is the primary cell involved with complications/untoward effects of healing and scarring, control over fibroblast survival during healing should allow the clinician to minimize the negative effects of scarring in select clinical circumstances, such as in burn wound contracture, GI anastomotic stricture, or cirrhosis. The candidate has hypothesized that matrix anchorage upregulates focal adhesion kinase activity, which in turn upregulates the PI3K/Akt survival pathway and inhibits the tumor suppressor p53, ultimately promoting cell survival. Loss of matrix anchorage is hypothesized to reverse these effects and induce apoptosis. The involvement of each protein will be probed with mutated isoforms.

描述（申请人提供）：候选人正在从事职业 学术手术是大学助理教授 内布拉斯加州医疗中心。他的临床兴趣包括微创和 机器人手术和腹壁手术他的基础科学兴趣 包括调节伤口愈合，肉芽组织的消退和 组织再生。他已经完成了为期6年的常规手术 （威斯康星州医学院），一项为期1年的奖学金 手术（MCW），以及与基础研究（伤口愈合）的3年奖学金 德克萨斯大学西南医学中心的弗雷德·吉因内尔（Fred Giinnell）。他的 短期目标是在壁外资金的帮助下建立职业 在UNMC的学术手术中。他的长期目标包括更大 了解愈合机制，朝着组织迈进 再生和最低侵入性和机器人手术的进步。 UNMC手术主席聘请了候选人，目的是 候选人将把他的75％的努力集中在研究和职业上 发展。候选人的职业发展计划涉及 基础科学研究，教学讲座，研讨会，专业课程， 科学会议，研究演讲和学术辩论/讨论。 候选人有3个赞助商：一位高级学术外科医生，一名外科医生 已建立的伤口愈合调查员，以及一名细胞生物学家 凋亡信号转导。后两个赞助商已获得NIH资助 实验室。候选人可以预见到4年的时间来执行拟议 实验并准备R01应用程序。 候选人的研究计划将调查成纤维细胞的调节 胶原基质中的生存。临床相关性是因为 成纤维细胞是涉及并发症/不良影响的主要细胞 康复和疤痕，对愈合过程中成纤维细胞存活的控制应 允许临床医生最大程度地减少疤痕中的负面影响 临床情况，例如在烧伤伤口签发中，GI吻合 狭窄或肝硬化。候选人假设矩阵锚固 上调焦点粘附激酶活性，这反过来上调 PI3K/AKT存活途径并抑制肿瘤抑制p53，最终 促进细胞存活。假设矩阵锚定的损失以逆转 这些作用并诱导凋亡。每种蛋白质的参与将是 用突变的同工型探测。