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Molecular genetic mechanisms of renal cell regeneration

肾细胞再生的分子遗传学机制

基本信息

批准号：
10205061
负责人：
Jeffrey Alan Beamish
金额：
$ 16.96万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10205061
关键词：
Acute Renal Failure with Renal Papillary Necrosis Affect Animal Model Animals Area Biocompatible Materials Bioinformatics Biology Cells Chromatin Chronic Kidney Failure Clinical Clinical Skills Complement Complex DNA Binding DNA Binding Domain Data Development Educational workshop Engineering Ensure Epigenetic Process Epithelial Epithelial Cell Proliferation Epithelial Cells Failure Female Genes Genetic Transcription Goals Homologous Protein Impairment Injury Injury to Kidney Kidney Kidney Diseases Link Measures Mediating Mentorship Mitosis Modeling Modification Molecular Genetics Mosaicism Mus Natural regeneration Nature Nephrology Pathway interactions Patients Phenotype Physiology Population Process Proteins Recovery Regenerative Medicine Regenerative pathway Reperfusion Injury Reporter Research Research Personnel Site System Testing Training Training Activity Transgenic Animals Tubular formation Work career cell regeneration differential expression engineering design epithelium regeneration experience experimental study histone methyltransferase histone modification insight kidney cell mutant nephrogenesis novel diagnostics novel therapeutics programs recruit regenerative biology renal epithelium single cell analysis symposium transcriptome

项目摘要

PROJECT SUMMARY/ABSTRACT The goals of this project are to 1) define the functions of Pax2 and Pax8 in recovery from kidney injury and 2) provide the candidate with detailed training to facilitate an independent research career in renal regenerative medicine. How the regeneration of renal epithelia is controlled remains poorly understood. Pax2 and Pax8 are two homologous proteins that are re-expressed in regenerating renal epithelia after kidney injury, but their function in these cells is unknown. Pax2 and Pax8 also are essential for normal kidney development and can recruit histone methyltransferase complexes that can modify chromatin accessibility. Our preliminary data show that selective deletion of Pax2 and Pax8 in the proximal tubule results in decreased renal epithelial proliferation and impaired recovery after kidney injury. These observations suggest the hypothesis that Pax2 and/or Pax8 regulate regeneration by promoting de-differentiation, entry into mitosis, and the reestablishment of epigenetic marks. Our first aim is to define the steps in renal epithelial regeneration that are dysregulated by Pax2 and Pax8 deletion. Our second aim is to identify critical regeneration pathways regulated by Pax2- and/or Pax8-mediated epigenetic modifications. These studies will form an experimental framework for training the candidate in the epithelial biology of renal regeneration, epigenetics, transgenic animals, animal models of kidney injury, and bioinformatics. Training at the bench will be supplemented with didactic courses, workshops, and conferences. A mentorship team of established investigators in renal regeneration, renal physiology, and bioinformatic analysis of kidney diseases has been assembled to guide the candidate through these experiments and training activities to ensure a successful transition to independence. New expertise in the biology of renal regeneration will augment the candidate’s prior experience in clinical nephrology and biomaterials engineering to enable an independent and unique career studying renal regeneration.

项目总结/文摘