BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10451503
• 负责人: Zheng Dong
• 金额: --
• 依托单位: CHARLIE NORWOOD VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2027-03-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451503
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Aging; Alternative Splicing; Apoptosis; Area; Autophagocytosis; Award; CHEK1 gene; Cancer Patient; Cardiovascular Diseases; Cell Cycle; Cell Death; Chronic Kidney Failure; Cilia; Cisplatin; Collaborations; Communication; DNA Damage; DNA Methylation; Development; Diabetes Mellitus; Diagnosis; Disease; Epigenetic Process; Fibroblasts; Funding; Grant; Health; Hypoxia; Impairment; Injury; Injury to Kidney; International; Kidney; Kidney Diseases; Laboratories; Lead; Malignant - descriptor; Medical; Mentors; MicroRNAs; Mitochondria; Mus; Natural regeneration; Nature; Normal tissue morphology; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pharmaceutical Preparations; Principal Investigator; Profibrotic signal; Publishing; Regulation; Renal carcinoma; Renal tubule structure; Reperfusion Injury; Reperfusion Therapy; Reporting; Repression; Research; Research Personnel; Role; STAT1 gene; Science; Scientist; Seminal; Services; Signal Pathway; TP53 gene; Time; Training; Tubular formation; United States National Institutes of Health; Veterans; Work; aging population; cancer therapy; career; chemotherapy; diabetic; diabetic patient; epigenetic regulation; hypoxia inducible factor 1; indexing; injury and repair; insight; interstitial; kidney fibrosis; mitochondrial metabolism; mortality; nephrotoxicity; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; renal ischemia; response

Dr. Dong is a nationally and internationally recognized investigator in the research field of kidney injury and repair. His current work is focused on mitochondria, metabolism, autophagy, and epigenetic regulation in kidney injury and repair under the disease conditions of renal ischemia- reperfusion, diabetes, and cisplatin nephrotoxicity. As of July 1, 2019, Dr. Dong has published 256 research articles that have been cited for over 20,000 times with H-index of 66, attesting his scientific contributions. Dr. Dong is currently the principal investigator on a VA Merit review award and two NIH RO1 grants. In the project of the VA Merit review award, Dr. Dong and colleagues will elucidate the mechanism of renal fibrosis after ischemia-reperfusion injury. Specifically, they will determine the role of renal tubular autophagy in kidney fibrosis after ischemia-reperfusion injury, delineate the involvement of hypoxia-inducible factor 1 (HIF-1) in autophagy activation, and identify the key profibrotic factors that are produced in renal tubules in an autophagy-dependent manner for interstitial fibroblast activation. By elucidating tubular autophagy in renal fibrosis after ischemia- reperfusion injury, this project may lead to the discovery of new therapeutic strategies. In the project of NIH 5R01DK058831, Dr. Dong and colleagues propose to investigate the mechanism underlying the heightened kidney injury sensitivity in diabetes. They will specifically determine the role of p53 in miR-214 induction in diabetic kidneys, delineate microRNA-214 (miR- 214) repression of ULK1, and elucidate autophagy impairment as a key to injury sensitivity in diabetic kidneys. Completion of this project will delineate a novel pathway of p53/miR- 214/ULK1 that leads to autophagy impairment and kidney injury sensitivity in diabetes. As a result, it may identify miR-214 and autophagy as novel therapeutic targets for kidney injury in diabetic patients. In the project of NIH 5R01DK087843, Dr. Dong and colleagues will investigate nephrotoxicity induced by cisplatin, one of the most widely used cancer therapy drugs. Specifically, they will elucidate mitophagy as a protective mechanism of autophagy in cisplatin-induced nephrotoxicity, determine the autophagy-promoting role of p53, and analyze the effects of PKCδ inhibition in autophagy-suppressed and non-suppressed mice. The research will not only gain insights into autophagy protection and regulation in renal pathogenesis, but will also elucidate autophagy as a mechanism of the renoprotective effect of PKCδ inhibition, suggesting novel therapeutic strategies for kidney protection during chemotherapy in cancer patients. In conclusion, Dr. Dong is an outstanding investigator who has made seminal contributions to the research field of kidney injury and repair, which are highly relevant to veterans’ health. In the ongoing projects funded by VA Merit and two NIH R01 grants, Dr. Dong will continue to make important discoveries that may lead to novel therapies for kidney diseases for the improvement of veterans’ health.

董博士是肾脏研究领域国内外公认的研究者 他目前的工作重点是线粒体、新陈代谢、自噬和修复。 肾缺血疾病条件下肾损伤和修复的表观遗传调控 截至 2019 年 7 月 1 日，Dong 博士发表了关于再灌注、糖尿病和顺铂肾毒性的文章。 256篇研究论文被引用超过20,000次，H指数为66，证明了他的研究成果 董博士目前是 VA 优异评审奖的首席研究员。 和两项 NIH RO1 拨款。 在VA Merit评审奖的项目中，Dong博士和他的同事将阐明 具体而言，他们将确定缺血再灌注损伤后肾纤维化的机制。 肾小管自噬在缺血再灌注损伤后肾纤维化中的作用 缺氧诱导因子 1 (HIF-1) 参与自噬激活，并确定关键 肾小管中以自噬依赖性方式产生的促纤维化因子 通过阐明缺血后肾纤维化中的肾小管自噬 再灌注损伤，这个项目可能会导致新的治疗策略的发现。 在NIH 5R01DK058831项目中，Dong博士和同事建议研究 糖尿病中脂肪肾损伤敏感性的潜在机制 确定 p53 在糖尿病肾脏中 miR-214 诱导中的作用，描绘 microRNA-214 (miR-214) 214）抑制 ULK1，并阐明自噬损伤是损伤敏感性的关键 该项目的完成将描绘出 p53/miR-214/ULK1 的新途径。 因此，可能会导致糖尿病的自噬损伤和肾损伤敏感性。 确定 miR-214 和自噬作为糖尿病患者肾损伤的新治疗靶点。 在NIH 5R01DK087843的项目中，Dong博士和同事将研究肾毒性 具体来说，他们将 阐明线粒体自噬作为顺铂诱导的肾毒性中自噬的保护机制， 确定p53的自噬促进作用，并分析PKCδ抑制作用 该研究不仅将深入了解自噬抑制和非抑制小鼠。 自噬在肾脏发病机制中的保护和调节，但也将阐明自噬作为 PKCδ 抑制的肾脏保护作用机制，提示治疗新 癌症患者化疗期间的肾脏保护策略。 总之，董博士是一位杰出的研究者，为 肾脏损伤与修复研究领域，与退伍军人健康密切相关。 董博士将继续开展由 VA Merit 和两项 NIH R01 拨款资助的正在进行的项目 可能导致肾脏疾病改善的新疗法的重要发现 退伍军人的健康。