Regulation of Fibroblast Survival in the Collagen Matrix

描述（由申请人提供）：候选人正在追求的职业生涯， 学术外科作为外科助理教授在大学 内布拉斯加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本科学兴趣 包括调节伤口愈合、肉芽组织消退， 组织再生他在普通外科完成了6年的住院医师实习 （威斯康星州医学院），一个为期1年的研究员在微创 外科（MCW），以及基础研究（伤口愈合）的3年奖学金， 德克萨斯大学西南医学中心的Fred Giinnell说。他 短期目标是在校外资金的帮助下， 在联合国医学中心做学术手术他的长期目标包括： 对愈合机制的理解，实现组织 再生，以及微创和机器人手术的进步。 联合国医务委员会外科主任雇用该候选人的意图是， 候选人将把75%的精力集中在研究和事业上 发展候选人？的职业发展计划包括以下几个方面 基础科学研究，教学讲座，研讨会，专业课程， 科学会议、研究报告和学术辩论/讨论。 候选人有3个赞助商：一个高级学术外科医生，一个外科医生是谁， 建立伤口愈合研究员，和细胞生物学家经验丰富， 凋亡信号转导后两个赞助商有NIH资助的 laboratories.候选人预计将在4年内执行拟议的 实验并准备R 01应用程序。 候选人的研究计划将调查成纤维细胞的调控 在胶原蛋白基质中存活。临床相关性在于， 成纤维细胞是涉及并发症/不良反应的主要细胞， 愈合和瘢痕形成，控制愈合过程中的成纤维细胞存活， 允许临床医生最小化瘢痕形成的负面影响， 临床情况，如烧伤创面挛缩、胃肠道吻合口 狭窄或肝硬化候选人假设基质锚定 上调粘着斑激酶活性，这反过来又上调 PI 3 K/Akt存活通路并最终抑制肿瘤抑制因子p53， 促进细胞存活。假设基质锚定丧失可逆转 这些影响并诱导细胞凋亡。每种蛋白质的参与将是 用突变的同种型探测

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.