BLR&D Research Career Scientist Award Application

Hidekazu(Hide)Tsukamoto博士继续为医疗事业做出重大贡献 退伍军人事务部在两个不同级别的研究方案：第一，作为 研究生理学家，在分子细胞机制方面有尖端发现 其次，他是P50国家中心的中心主任 关于酒精性肝和胰腺疾病(ALPD)和肝硬变的计划 以及以成果为导向支持退伍军人管理局调查人员在区域和跨地区的科学工作 这个国家。 在过去的10年里，他发表了71篇同行评议文章，并保持着联邦拨款 当前直接成本总额每年超过110万美元(不包括所有中心组件)。他 对有关形态原介导的细胞周期调控的新知识做出了重大贡献 肝星状细胞(HSCs)、肝巨噬细胞和肿瘤起始干细胞样细胞的细胞命运 细胞(TICS)，在肝纤维化、炎症和癌症中发挥关键作用的细胞类型， 分别进行了分析。在这些规则中，新陈代谢重新编程的新模式被披露为 潜在的机制。更具体地说，Notch介导的促炎M1激活 肝巨噬细胞与线粒体代谢重编程有因果关系(J Clin Invest 2015年；125：1579-90)。WNT诱导的HSCs活化是由脂质代谢介导的 涉及硬脂酰辅酶A脱饱和酶(SCD)的重新编程(胃肠病学2017；152：1477-91)。 此外，由HSCs表达的SCD被证明在 促进肝肿瘤进展的微环境。 在程序上，他继续指导一个全国知名的P50中心项目 酒精性肝胰腺疾病与一体化肝细胞R24核心计划 支持前沿ALPD研究的技术。通过这些节目，他 合作并支持12名退伍军人管理局调查人员，并指导了10名初级教员 VARCS奖的当前周期。 从本质上讲，Tsukamoto博士的努力对个人和集体都产生了影响 他和全国各地的许多退伍军人管理局调查人员所追求的科学，并帮助识别 VA患者中常见的ALPD和肝硬变的治疗目标。

Dr. Hidekazu (Hide) Tsukamoto continues to make significant contributions to the Medical Research Program of the Department of Veterans Affairs at two distinct levels: first as a Research Physiologist who makes cutting-edge discoveries on molecular cellular mechanisms of liver fibrosis and cancer; and secondly as a Center Director of the P50 national center program on alcoholic liver and pancreatic diseases (ALPD) and cirrhosis who renders concrete and outcome-oriented support for scientific endeavors of VA investigators regionally and across the nation. He published 71 peer-review articles in the last 10 years and maintained federal grants with total current direct costs exceeding $1.1M per year (not inclusive of all center components). He has made major contributions to new knowledge concerning morphogen-mediated regulation of cell fate of hepatic stellate cells (HSCs), hepatic macrophages, and tumor-initiating stem-like cells (TICs), the cell types shown to play critical roles in liver fibrosis, inflammation, and cancer, respectively. In these regulations, novel modes of metabolic reprogramming were disclosed as underlying mechanisms. More specifically, Notch-mediated proinflammatory M1 activation of liver macrophages is causally linked to mitochondrial metabolic reprogramming (J Clin Invest 2015;125:1579-90). Wnt-induced activation of HSCs is mediated by lipid metabolic reprogramming involving stearoyl CoA desaturase (SCD) (Gastroenterology 2017;152:1477-91). Further, SCD expressed by HSCs is shown to achieve tumor-promoting lipid reprogramming in microenvironment to enhance liver tumor progression. Programmatically, he continues to direct a nationally renowned P50 center program on alcoholic liver and pancreatic diseases and a R24 core program on integrative liver cell techniques which support leading-edge ALPD research. Through these programs, he collaborated and supported 12 VA investigators and mentored 10 junior faculty members during the current cycle of the VARCS award. In essence, the efforts Dr. Tsukamoto makes, render individual and collective impacts on science pursed by him and many VA investigators across the nation and help identify therapeutic targets for ALPD and cirrhosis which are prevalent in VA patients.