Differential Gene Expression in Keloids

描述（由申请人提供）：瘢痕疙瘩是一种潜伏的疾病过程，主要困扰年轻的少数民族患者，使他们毁容，偶尔残疾。该研究申请旨在解决以下观察结果，即与正常来源的皮肤细胞相比，瘢痕疙瘩来源的皮肤细胞似乎对血清刺激和物理应变形式的应激具有异常的基因型反应。这种现象将通过关注TGF-β 2基因对角质形成细胞中血清刺激的差异转录反应来检查。本申请的三个具体目的是确定负责这种差异反应的启动子元件，鉴定介导反应的信号转导途径，并鉴定可能与TGF-β 2协同调节并促成瘢痕疙瘩表型的其他基因。除了回答有关瘢痕疙瘩生物学的重要问题，这个应用程序也将服务！为主要研究者的学术生涯提供支持。他长期致力于生物医学研究，并选择了伤口愈合和手术作为他希望追求的领域。他最初的目标是建立一个伤口愈合实验室，通过校外资金完全支持。主要研究者的长期目标是利用他在伤口愈合研究中获得的知识，更好地了解皮肤生物学。然后，这些信息可以通过治疗慢性伤口或过度疤痕转化为临床应用，也可以用于组织工程合成人造皮肤，可应用于重建中的临床问题，包括烧伤。详细介绍了职业发展计划，旨在教育主要研究者正确、道德地进行研究。本集团已制定计划以提高特定技能，促进彼之职业发展。这些包括实验设计，granimetry，与外科和科学界的互动，以及手稿的准备和审查。该项目将在斯坦福大学医学院一位非常成功的导师的指导下进行。这是美国领先的生物医学研究机构之一，它已经实施了多个旨在改善转化医学的项目。该机构拥有开展这一项目所需的一切资源，此外还拥有该领域的一些专家提供咨询意见。

DESCRIPTION (provided by applicant): Keloids represent an insidious disease process that afflicts primarily young, minority patients leaving them with disfigurement, and occasionally, disability. This research application seeks to address the observation that keloid-derived skin cells appear to have an aberrant genotypic response compared to normal-derived skin cells to stress in the form of serum stimulation and physical strain. This phenomenon will be examined by focusing on the differential transcriptional response of the TGF-beta2 gene to serum stimulation in keratinocytes. The three specific aims of this application are to determine the promoter elements responsible for this differential response, identify the signal transduction pathways mediating the response, and identify additional genes that may be coordinately regulated with TGF-beta2 and contributing to the keloid phenotype. In addition to answering important questions about keloid biology, this application will also serve !to provide the nit a support for the academic career of the Principal Investigator. He has demonstrated a long record of commitment to biomedical research and has chosen wound healing and surgery as the field he wishes to pursue. His initial goal is to establish a laboratory in wound healing that is fully supported through extramural funding. The long term goal of the Principal Investigator is to use the knowledge derived from his studies in wound healing to better understand the biology of skin. This information can then be translated into clinical applications through the treatment of chronic wounds or excessive scarring, and can also be used in tissue engineering to synthesize artificial skin that can be applied to clinical problems in reconstruction, including burns. A career development program is detailed that is designed to educate the Principal Investigator in the proper, ethical conduct of research. Plans have been developed to improve specific skills to promote his career development. These include experimental design, grantsmanship, interactions with the surgical and scientific community, and manuscript preparation and review. This project will be carried out under the tutelage of a highly successful Mentor at Stanford University Medical School. This is one of the leading biomedical research institutions in the nation, and it has implemented multiple programs aimed at improving translational medicine. The institution has every resource needed to carry out this project in addition to a number of experts in the field to provide advice.