BLR&D Research Career Scientist Award Application

董博士是国内和国际公认的肾脏研究领域的研究员。 受伤和修复。他目前的工作集中在线粒体、新陈代谢、自噬和 肾缺血疾病条件下肾损伤修复的表观遗传学调控 再灌注、糖尿病和顺铂肾毒性。截至2019年7月1日，董博士发表了 被引用超过2万次的研究论文256篇，H指数为66，证明了他的观点 科学贡献。董博士目前是退伍军人事务部功勋审查奖的首席研究员 和两笔NIH RO1拨款。 在退伍军人事务部荣誉评审奖的项目中，董博士和同事们将阐明 肾缺血再灌注损伤后肾纤维化的机制。具体来说，他们将确定 肾小管自噬在肾缺血再灌注损伤后肾纤维化中的作用 低氧诱导因子1(HIF-1)参与自噬激活，并确定关键 以自噬依赖的方式在肾小管中产生的促纤维化因子 间质成纤维细胞活化。通过阐明肾小管自噬在缺血后肾纤维化中的作用- 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，董博士和他的同事们建议调查 糖尿病患者肾脏损伤敏感性升高的机制。他们将明确表示 确定p53在糖尿病肾脏miR-214诱导中的作用，描绘microRNA-214(miR-214) 214)抑制ULK1，并阐明自噬损伤是伤害敏感性的关键 糖尿病肾脏。该项目的完成将勾画出一条新的p53/miR-214/ULK1通路 这会导致糖尿病患者的自噬功能受损和肾脏损伤敏感性。因此，它可能会 确定miR-214和自噬为糖尿病患者肾脏损伤的新治疗靶点。 在NIH 5R01DK087843项目中，董博士和他的同事将研究肾脏毒性 顺铂是目前应用最广泛的癌症治疗药物之一。具体来说，他们将 阐明有丝分裂吞噬是顺铂肾毒性中自噬的保护机制， 检测P53的自噬促进作用，并分析抑制PKCδ的作用。 自噬被抑制和非被抑制的小鼠。这项研究不仅将获得对 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 抑制蛋白激酶Cδ的肾脏保护作用机制，提示新的治疗方法 癌症患者化疗期间肾脏保护的策略。 总而言之，董博士是一位杰出的研究人员，他对 肾脏损伤与修复的研究领域，与退伍军人的健康高度相关。在 正在进行的由VA Merit和两个NIH R01赠款资助的项目，董博士将继续 重要发现，可能导致肾脏疾病的新疗法的改善 退伍军人的健康状况。

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.