Identification and functional analysis of renal stem cells

肾干细胞的鉴定及功能分析

• 批准号: 7482452
• 负责人: ROSEMARY V SAMPOGNA
• 金额: $ 13万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-09 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7482452
• 关键词: Acute Kidney Failure; Acute Kidney Tubular Necrosis; Address; Adult; Analgesics; Animal Model; Antibodies; Area; Award; Behavior; Biochemistry; Biological; Biopsy; Cell Cycle; Cells; Cellular biology; Clinical; Condition; Cues; Data; Depth; Detection; Development; Diagnostic; Disease; Doctor of Philosophy; Embryo; End stage renal failure; Environment; Epithelial; Equilibrium; Evolution; Fellowship; Genetic Transcription; Goals; Hematopoietic stem cells; Human; Hypoxia; Injury; Internal Medicine; Invasive; Investigation; Kidney; Kidney Diseases; Kidney Papilla; Kidney Part; Label; Laboratories; Lead; Life; Localized; Mediating; Medical; Mentored Clinical Scientist Development Award (K08); Methodology; Methods; Microscopy; Molecular; Morbidity - disease rate; Mus; Nephrology; Numbers; Organ; Papillary; Phenotype; Physiologic pulse; Population; Prevalence; Process; Proliferating; Property; Protein Overexpression; Public Health; Pulse taking; Rattus; Regulation; Renal function; Reperfusion Injury; Research Personnel; Residencies; Role; Rosemary; Scientist; Sickle Cell Anemia; Signal Transduction; Skin; Sorting - Cell Movement; Source; Stem cells; Stimulus; Structure; Techniques; Therapeutic; Thinking; Time; Tissues; Training; Transcript; Ureteral obstruction; adult stem cell; base; body system; cell behavior; cell injury; human tissue; improved; in vivo; insight; interest; kidney cell; mortality; multipotent cell; nephrogenesis; programs; relating to nervous system; repaired; research study; response; restoration; skills; tissue culture; tissue regeneration; tongue papilla; tool; transcription factor

DESCRIPTION (provided by applicant): This is an application for a Mentored Clinical Scientist Development Award (K08) entitled "Identification and Functional Analysis of Renal Stem Cells." The candidate holds MD and PhD degrees, has completed a residency in Internal Medicine and a fellowship in Nephrology. During this award, the candidate will acquire the background and laboratory skills required to further develop as a clinical scientist in the areas of renal disease and kidney development. The goals of the proposal are: (1) To identify a specific cell marker that is unique to label retaining cells in the kidney papilla and can be used to enrich and track this population; (2) To delineate the function of kidney label retaining cells in vivo before and after injury; and (3) To identify and delineate the function of regulatory molecules in kidney label retaining cells that mediate injury in acute tubular necrosis and obstructive nephropathy. The proposed studies utilize techniques in tissue culture, microscopy, molecular and cell biology, and this program of research and study will strengthen and advance the training of the candidate in these areas. The candidate proposes an integrated program of study and research directed toward improved understanding of reparative processes and, more specifically, the response of renal progenitor cells to injury. Indeed, an ever-increasing number of investigations demonstrate that tissue regeneration occurs throughout adult life, often in organ systems thought to be irreparable. Such studies point to the post-injury restoration of biological structure and function via cell-replacement strategies. The need for a deep understanding of stem cell behavior is central to confronting these issues. Relevance of this proposal to public health: the prevalence of acute renal failure in the hospitalized setting remains high and multiplies in the setting of increased co-morbid conditions. Moreover, diseases initially involving the renal papilla such as analgesic nephropathy and sickle cell anemia often lead to more global renal injury and can lead to end stage renal disease. Only by understanding the molecular signaling that underlies the "sensing" of renal injury as well as the initiation of repair, will we be able to initiate application of this new methodology to long-standing medical problems in nephrology.

描述（由申请人提供）： 这是一个指导临床科学家发展奖（K 08）的申请，题为“肾干细胞的识别和功能分析。“候选人拥有医学博士和博士学位，已完成内科住院医师和肾脏病学研究金。在此期间，候选人将获得进一步发展为肾脏疾病和肾脏发育领域的临床科学家所需的背景和实验室技能。本研究的目的是：（1）鉴定一种特异性的细胞标记物，该标记物可用于标记肾乳头中的滞留细胞，并可用于富集和追踪这一群体;（2）描述肾标记物滞留细胞在损伤前后的体内功能;以及（3）确定和描述肾脏标记保留细胞中调节分子的功能，这些细胞介导急性肾小管坏死和梗阻性肾小管损伤。肾病拟议的研究利用组织培养，显微镜，分子和细胞生物学技术，这一研究和学习计划将加强和促进候选人在这些领域的培训。 候选人提出了一个综合的学习和研究计划，旨在提高对修复过程的理解，更具体地说，肾祖细胞对损伤的反应。事实上，越来越多的研究表明，组织再生发生在整个成年生活中，通常发生在被认为是不可修复的器官系统中。这些研究指出了通过细胞替代策略恢复损伤后的生物结构和功能。深入了解干细胞行为的必要性是解决这些问题的核心。 该提案与公共卫生的相关性：住院环境中急性肾衰竭的患病率仍然很高，并且在合并症增加的情况下成倍增加。此外，最初涉及肾乳头的疾病，如镇痛性肾病和镰状细胞性贫血，通常会导致更多的整体肾损伤，并可能导致终末期肾病。只有通过了解分子信号的基础上的“传感”的肾损伤，以及修复的启动，我们将能够启动应用这种新的方法来长期存在的医学问题在肾脏病学。