Identification and functional analysis of renal stem cells

肾干细胞的鉴定及功能分析

• 批准号: 7319589
• 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/7319589
• 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; 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)： 这是一份名为“肾干细胞的鉴定和功能分析”的临床科学家发展指导奖(K08)的申请书。应聘者拥有医学博士学位，已完成内科住院医师和肾脏病学研究员学位。在这个奖项期间，候选人将获得所需的背景和实验室技能，以进一步发展为肾脏疾病和肾脏开发领域的临床科学家。该提案的目标是：(1)确定一个特定的细胞标记物，该标记物是肾乳头中标记保留细胞所特有的，可用于丰富和跟踪这一群体；(2)描述肾脏标记保留细胞在损伤前后在体内的功能；以及(3)识别和描述肾标记保留细胞中调节分子在急性肾小管坏死和梗阻性肾病中介导损伤的功能。拟议的研究利用了组织培养、显微镜、分子和细胞生物学的技术，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。 候选人提出了一个学习和研究的综合计划，旨在改善对修复过程的理解，更具体地说，是肾脏前体细胞对损伤的反应。事实上，越来越多的研究表明，组织再生贯穿整个成年生活，通常发生在被认为是无法修复的器官系统中。这类研究指出，通过细胞替换策略，损伤后生物结构和功能的恢复。需要深入了解干细胞的行为是面对这些问题的核心。 这一建议与公共卫生的相关性：在住院环境中急性肾功能衰竭的患病率仍然很高，在合并疾病增加的情况下还会成倍增加。此外，最初累及肾乳头的疾病，如止痛性肾病和镰状细胞性贫血，往往会导致更多的全局性肾损伤，并可能导致终末期肾脏疾病。只有了解了肾脏损伤的“感觉”以及修复的启动的分子信号，我们才能开始应用这一新的方法学来解决肾脏病中长期存在的医学问题。