Cellular repair in acute kidney injury

急性肾损伤的细胞修复

• 批准号: 8392099
• 负责人: LISA M CURTIS
• 金额: --
• 依托单位: BIRMINGHAM VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8392099
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Address; Aging; Alabama; Animal Model; Animals; Binding; Biochemical Markers; Biochemistry; Biological Assay; Biology; Cell physiology; Cells; Cellular biology; Chronic; Chronic Kidney Failure; Clinical; Complement; Development; Development Plans; Dialysis procedure; Dose; Educational workshop; End stage renal failure; Environment; Epithelium; Feedback; Functional disorder; Genetic; Goals; Growth Factor; Hepatocyte Growth Factor; Histologic; Human; Immunohistochemistry; Individual; Injury; Innovative Therapy; K-Series Research Career Programs; Kidney; Kidney Papilla; Medical center; Medicine; Mentors; Mentorship; Microbiology; Modality; Molecular; Molecular Biology; Monitor; Morbidity - disease rate; Natural regeneration; Nephrology; Outcome; Papillary; Pathway interactions; Patients; Physicians; Physiology; Population; Process; Recovery; Recruitment Activity; Renal function; Renal tubule structure; Reperfusion Injury; Research; Research Personnel; Risk; Role; Secondary to; Severities; Signal Pathway; Signal Transduction; Site; Source; Stromal Cell-Derived Factor 1; Supplementation; System; Techniques; Testing; Therapeutic; Therapeutic Intervention; Tissues; Training; Transgenic Animals; Translations; Universities; Veterans; Work; base; career development; cell motility; chemokine; clinical care; clinically relevant; experience; implantation; improved; in vivo; in vivo Model; inhibitor/antagonist; injured; injury and repair; insight; interstitial; interstitial cell; kidney cell; meetings; member; migration; model design; mortality; neutralizing antibody; novel; post-doctoral training; professor; programs; receptor; reconstitution; repaired; research study; response; response to injury; responsible research conduct; tongue papilla; tool

DESCRIPTION (provided by applicant): The primary goal of this research program is to provide the applicant, Dr. Lisa M. Curtis, with new and intensive training in cell signaling and renal physiology and pathophysiology to expand her research tools with the purpose of becoming an independent VA investigator. To achieve this goal, Dr. Curtis will train in the fertile environment of the Birmingham VAMC and the University of Alabama at Birmingham (UAB), under the sponsorship of Paul W. Sanders, MD, Chief, Renal Section of the Birmingham VAMC and a Professor of Medicine at UAB. Additional mentoring will be provided by Dr. Anupam Agarwal, a staff physician at the Birmingham VAMC and Professor of Medicine and Division Director of Nephrology at UAB, and Dr. Christopher A. Klug, a Professor of Microbiology, Biochemistry and Genetics at UAB. Drs. Sanders, Agarwal and Klug have extensive experience in mentorship and have previously jointly provided Dr. Curtis with mentorship during her postdoctoral training at UAB. They each have unique expertise to facilitate accomplishing the scientific and professional training of Dr. Curtis that is necessary to achieve her long-term goals. The proposed studies will be the basis for training the applicant in the process used to study signaling pathways, particularly as applied to the study of hepatocyte growth factor (HGF) and stromal cell-derived factor 1 (SDF-1) , two known modulators of the pathophysiology of cellular repair in acute kidney injury (AKI). Additionally, these studies will expand the applicant's expertise in classical cell and molecular biology with an emphasis on renal pathophysiology. The scientific goals of this proposal are to elucidate the identity of renal cells that are capable of reconstitution of renal tubules and the signaling necessary to induce this reparative response. The overall hypothesis of the proposal is that renal reparative cells reside in the Fsp1+ cell population of the renal papilla and are recruited to sites of injury in response to the specific factors, HGF and SDF- 1. The proposal is divided into two specific aims. The first aim utilizes an in vivo model of ischemia- reperfusion injury (IRI), a clinically relevant animal model, designed to elucidate the identity and dose-response of reparative cells that are recruited from the renal papilla in response to signals from the injured tissue. This aim utilizes the powerful technique of the Cre-lox system in transgenic animals to mark specific cell populations in the kidney, which can then be tracked by histochemical and immunohistochemical techniques. The second aim uses IRI to ascertain the impact of the presence or absence of signaling by HGF and/or SDF-1 on the repair of the epithelium. This aim uses interference in the signaling pathways of these two agents through the use of neutralizing antibodies or pharmacologic agents. Similar to the first aim, this aim utilizes the outcome of the migration and incorporation of the marked reparative cells; as well, other indicators of injury and repair in AKI will be monitored for alterations. The career development plan includes attendance at seminars, workshops and other educational training opportunities at UAB, such as an advanced course in cell signaling, as well as training in the responsible conduct of research. The applicant will interact with senior members of the Renal Section, VAMC and the UAB Division of Nephrology. The Mentoring Plan includes formal and informal meetings with her three mentors, individually and together, which provide opportunities to address her training as an independent investigator as well as providing her with feedback on her professional and scientific progress. This Career Development Award will greatly enhance the applicant's professional development towards becoming an independent VA investigator.

描述（由申请人提供）：