Mitochondrial Protection to Derive Expanded Aged Renal Glomerular Progenitor Cells

线粒体保护以衍生扩大的老化肾小球祖细胞

• 批准号: 10593049
• 负责人: Mariya Ts'ana Sweetwyne
• 金额: $ 12.38万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10593049
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adult; Affect; Age; Aging; Animals; Area; Autologous Stem Cell Transplantation; Award; Binding; Biology; Biology of Aging; Biopsy; Blood capillaries; Board Certification; Cardiolipins; Cell Aging; Cell Count; Cell Culture Techniques; Cell Cycle; Cell Density; Cell Lineage; Cell Proliferation; Cells; Cellular biology; Characteristics; Chronic; Chronic Kidney Failure; Clinical; Clinical Research; Collaborations; Collagen Type IV; Darkness; Development; Development Plans; Diabetes Mellitus; Doctor of Philosophy; Elderly; Environment; Epithelial Cells; Epithelium; Excretory function; Filtration; Future; Genus Hippocampus; Glomerular capsule structure; Goals; Health; High Fat Diet; Human; Hypertension; In Vitro; Injury; Injury to Kidney; Inner mitochondrial membrane; Intervention; Investments; K-Series Research Career Programs; Kidney; Kidney Diseases; Lesion; Life; Light; Measurement; Mediating; Membrane; Mentors; Mesenchymal; Methods; Mitochondria; Molecular; Morphology; Mus; Muscle; Nephrology; Operative Surgical Procedures; Opportunistic Infections; Outcome Measure; Oxidative Phosphorylation; Oxidative Stress; Parietal; Pathologist; Pathology; Pathway interactions; Phenotype; Phospholipids; Population; Predisposition; Proteomics; Radiology Specialty; Regenerative capacity; Rejuvenation; Renal glomerular disease; Research; Research Activity; Respiration; Risk; Role; Rotenone; Schedule; Therapeutic; Therapeutic Intervention; Training; Training Activity; Universities; Urine; Washington; Work; age related; aged; beta-Galactosidase; career; career development; cell age; chemotherapy; comorbidity; design; experimental study; fluorescence imaging; functional outcomes; glomerular filtration; glomerulosclerosis; healing; improved; in vivo; injured; kidney cell; man; meetings; mesangial cell; mitochondrial dysfunction; multidisciplinary; peroxidation; podocyte; postmitotic; preservation; progenitor; programs; regeneration potential; renal damage; renal epithelium; resilience; response; senescence; senior faculty; sex; stem cells; success; symposium; tool; treatment arm; urinary; young adult

Abstract: Mitochondrial Protection to Derive Expanded Aged Renal Glomerular Progenitor Cells Candidate: This K01 career development award application describes research and training activities for Mariya T. Sweetwyne, Ph.D. a renal cell biologist in the department of Pathology at the University of Washington, Seattle. Her immediate career goal is to combine her established training in renal biology with newly acquired and on-going training in the biology of cellular aging. Long-term, she intends to build an independent research program focused on developing interventions to ameliorate the impact of cellular aging on both chronic and acute renal glomerular diseases. In this application, Dr. Sweetwyne proposes specific aims to determine the role of mitochondrial dysfunction on the pathologies of aging glomerular epithelial cells. Research: Aging in the kidney is marked by fibrotic changes to the glomerular filtration units, which lead to increased risk of developing chronic kidney disease with advancing age. Previous studies from Dr. Sweetwyne et al. demonstrated that treating old mice with a tetrapeptide, Elamipretide (SS-31/Bendavia), to preserve mitochondrial inner membrane structure significantly reduced glomerular damage from renal aging, suggesting that one key to renal plasticity in the aged lies in mitochondrial health. This proposal builds on those findings to ask: (Aim 1) which aspect of mitochondrial function is improved in specific glomerular epithelial cells, (Aim 2) how mitochondrial improvement results in observed reduction of glomerular cell senescence, (Aim 3) and whether these known enhancements will affect the regenerative potential of aged and depleted renal progenitor cells in mouse and man. Career Development Plan: This proposal serves Dr. Sweetwyne’s short and long-term goals by building her bench expertise in the biology of aging in three critical areas: (1) assessment of mitochondrial energetics, (2) utilization of proteomics, and (3) isolation and culture of primary human urine-derived progenitor cells. Professional academic development activities include: formal graduate course work in the biology of aging, presentation of research at national scientific conferences and routinely scheduled meetings with career mentors. Environment: The environment for Dr. Sweetwyne’s training at the University of Washington (UW) is exceptional. Her multidisciplinary mentoring team is comprised of senior faculty who are experts in mitochondrial energetics, aging biology, or nephrology. Dr. Sweetwyne’s principal mentor, Dr. Rabinovitch, is recognized as a leader in the field of aging and has successfully mentored multiple trainees through K01 and K99/R00 awards. Co-mentor Dr. David Marcinek of UW Radiology is an expert in mitochondrial energetics and oxidative stress in aging or injured muscle. Co-mentor Dr. Behzad Najafian of UW Pathology is a board certified Clinical Renal Pathologist and is expert in culture of human renal glomerular epithelium isolated from biopsies and urine. All mentors have established professional collaborations with Dr. Sweetwyne and are thus invested in the success of the scientific and professional aims outlined herein.

摘要：线粒体保护作用在老年扩大肾肾小球祖细胞中的应用