Dissect stress response in skin epithelial wounding and hyperproliferative disorders

剖析皮肤上皮损伤和过度增殖性疾病的应激反应

• 批准号: 10371881
• 负责人: Yejing Ge
• 金额: $ 13.47万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10371881
• 关键词: ATAC-seq; Academic skills; Acute; Address; Affect; Apoptosis; Atmosphere; Automobile Driving; Award; Basic Science; Biological Assay; Biology; CRISPR/Cas technology; Candidate Disease Gene; Cellular Stress; Chromatin; Clinic; Clustered Regularly Interspaced Short Palindromic Repeats; Communication; Communities; Data; Development; Disease; Doctor of Philosophy; Elements; Engineering; Ensure; Environment; Epithelial; Family; Foundations; Future; Gene Expression Regulation; Genes; Genetic; Genetic Engineering; Genome; Genomic approach; Goals; Homeostasis; Human; Hyperplasia; Individual; Institution; Knock-out; Knowledge; Leadership; Malignant - descriptor; Malignant Neoplasms; Maps; Mediating; Mentors; Methods; MicroRNAs; Microinjections; Microscopy; Modeling; Molecular; Molecular Biology; Mosaicism; Natural regeneration; Oncogenic; Pathway interactions; Phenotype; Physiological; Positioning Attribute; Postdoctoral Fellow; Procedures; Process; Property; Reagent; Regulation; Reporter; Research; Resistance; Rest; Sampling; Signal Transduction; Skin; Skin Cancer; Stress; System; Technical Expertise; Testing; Tetracyclines; Therapeutic; Thinking; Time; Tissues; Training; Tumor Stem Cells; Universities; Untranslated RNA; Work; Writing; Xenograft procedure; adult stem cell; base; biochemical tools; biological adaptation to stress; candidate validation; cell behavior; cell motility; epithelial wound; experience; functional genomics; genetic signature; healing; human disease; human tissue; improved; in utero; in vivo; innovation; insight; interest; literacy; migration; mouse model; myogenesis; neoplastic; novel; overexpression; programs; repaired; restoration; self-renewal; skeletal; skills; skin disorder; skin regeneration; skin wound; stem cell fate; stem cell function; stem cell homeostasis; stem cell proliferation; stem cells; stemness; tenure track; tissue stem cells; tool; transcription factor; transcriptome; tumor; tumor progression; tumorigenesis; ultrasound; wound; wound healing

Project Summary During my PhD, I used skeletal myogenesis as my model to dissect signal transduction and gene regulation mechanisms. I have obtained technical literacy over a wide range of molecular biology and biochemical tools, accumulated critical experience on genetic mouse models, and developed critical and analytical thinking skills in experimental biology. I also came to appreciate the power of functional genomics, My so far 4.5-year's postdoc training focuses on interrogating molecular drivers in skin tumorigenesis fueled by stem cells, applying principles of functional genomics in mouse models, and validating findings in human clinic samples and xenografts. These training had expanded my research horizon, matured my experimental skills, and laid groundwork for me to ask important questions in human diseases. As I extend my training due to unexpected family difficulties, it would be essential for me to acquire additional scientific and academic skills that will enable me to gain full research autonomy and develop an innovative basic research program addressing fundamental questions in development and diseases. Over the past decades, we start to understand some of the molecular mechanisms involved in wound repair. We have also acquired substantial insights into oncogenic and tumor suppressive pathways in cancer. However, despite the long posited hypothesis that cancer is a wound that never heals, it is still unclear whether wounds and cancer functionally rely on the same stress components and if so, at which point they diverge. These are the primary focus of my current and future proposed research. I will establish and expand tools based on non- germline genetically engineered mosaic mouse models using in utero transduced CRISPR reagents. I will apply functional genomic approaches to prioritize and screen a focused list of stress relevant genes in driving wound repair and cancer. I will delineate molecular mechanisms that steer the long sought bifurcation point between the two stress conditions, and validate the physiological relevance of top my candidate stress genes in human samples. This knowledge will add to our understanding of the molecular mechanisms during cellular stress, and help to improve therapeutic treatments in skin wounds, hyperplasic diseases, and cancer. With the stimulating atmosphere provided by the Fuchs lab, the Rockefeller University, the Tri- Institution, and the broader NYC scientific community, I found myself positioned within an exceptional environment to pursue my ambition. If awarded, I will further obtain training in 1) technical skills – sequencing, advanced microscopy, CRISPR technology; and 2) personal development – writing, communication, mentoring, leadership, and management. My goal is, during the final years of K01, land in an independent tenure-track position with top-tier vibrating environment, especially those with an intensive emphasis on non-coding biology, where I will establish my own innovative, viable and sustainable research program in skin diseases and cancer.

项目摘要 在我的博士学位期间，我用骨骼肌发生作为我的模型来剖析信号转导和基因 调控机制我已经获得了广泛的分子生物学技术知识， 生物化学工具，积累了遗传小鼠模型的关键经验，并开发了关键和 实验生物学中的分析思维能力。我也开始欣赏功能基因组学的力量， 到目前为止，我的4.5年博士后培训的重点是询问皮肤肿瘤发生中的分子驱动因素 在小鼠模型中应用功能基因组学原理，并验证 人临床样品和异种移植物。这些训练拓展了我的研究视野，使我的 实验技能，并为我提出人类疾病的重要问题奠定了基础。 由于意外的家庭困难，当我延长培训时间时，我必须获得 额外的科学和学术技能，这将使我能够获得充分的研究自主权，并制定一个 创新的基础研究计划，解决发展和疾病的基本问题。来 在过去的几十年里，我们开始了解一些涉及伤口修复的分子机制。我们有 还获得了大量的见解致癌和肿瘤抑制途径的癌症。但尽管 尽管长期以来假设癌症是一种永远不会愈合的伤口，但仍然不清楚伤口和 癌症在功能上依赖于相同的压力成分，如果是这样，那么它们在哪一点上是不同的。这些都是 这是我目前和未来研究的重点。我将建立和扩展基于非- 使用子宫内转导的CRISPR试剂的种系基因工程嵌合小鼠模型。我会 应用功能基因组学方法，优先考虑并筛选出一系列与驾驶应激相关的基因 伤口修复和癌症我将描述引导长期寻求的分叉点的分子机制， 两种应激条件之间的差异，并验证我的候选应激基因的生理相关性 在人体样本中。这些知识将增加我们对细胞凋亡过程中分子机制的理解。 压力，并有助于改善皮肤伤口，增生性疾病和癌症的治疗。 在福克斯实验室、洛克菲勒大学、三- 机构，以及更广泛的纽约科学界，我发现自己处于一个特殊的位置， 环境，追求我的野心。如果被授予，我将进一步获得培训1）技术技能-排序， 先进的显微镜，CRISPR技术;和2）个人发展-写作，沟通，指导， 领导和管理。我的目标是，在K01的最后几年，在一个独立的终身教职轨道土地 在顶级振动环境中的位置，特别是那些高度重视非编码生物学的位置， 在那里，我将建立自己的创新，可行和可持续的皮肤病和癌症研究计划。