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: 6800063
• 负责人: MARK A CARLSON
• 金额: $ 11.02万
• 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/6800063
• 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（由申请人提供）：候选人正在寻求职业生涯