Nutrient-sensing GHS-R in macrophage reprogramming and inflamm-aging

巨噬细胞重编程和炎症衰老中的营养感应 GHS-R

• 批准号: 10809514
• 负责人: YUXIANG SUN
• 金额: $ 14.5万
• 依托单位: TEXAS A&M AGRILIFE RESEARCH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10809514
• 关键词: Ablation; Adipocytes; Adipose tissue; Administrative Supplement; Age; Aging; Anti-Inflammatory Agents; Attenuated; Award; Binding; Biology; Bone Marrow; Budgets; Career Mobility; Cell Aging; Cells; Chronic; Chronic Disease; Coculture Techniques; Deposition; Diabetes Mellitus; Diet; Dimensions; Disease; Education; Energy Metabolism; Equipment; Exhibits; Fee-for-Service Plans; Funding; G-Protein-Coupled Receptors; GTP-Binding Proteins; Generations; Goals; Grant; Hepatic; Hepatocyte; High Fat Diet; Hormones; Immune; Immunity; Immunotherapeutic agent; Impairment; In Vitro; Infiltration; Inflammaging; Inflammation; Inflammatory; Institution; Insulin Resistance; Investigation; Knockout Mice; Kupffer Cells; Lasers; Link; Lipids; Lipopolysaccharides; Liver; Liver Dysfunction; Longevity; LoxP-flanked allele; Macrophage; Manuscripts; Mediating; Metabolic; Metabolic Diseases; Metabolic Pathway; Metabolic dysfunction; Metabolic stress; Molecular; Morphology; Muramidase; Mus; Myelogenous; Nature; Obesity; Palmitates; Paper; Pathogenesis; Pathologic; Pathologic Processes; Peer Review; Peripheral; Phenotype; Physiological; Prevention; Process; Productivity; Protein Subunits; Publishing; Reporting; Research; Role; Signal Transduction; Steatohepatitis; Texas; Thinness; Tissues; Universities; Work; biological research; cytokine; detection of nutrient; diet-induced obesity; dietary; frontier; ghrelin; ghrelin receptor; growth hormone secretagogue receptor; healthspan; improved; in vivo; insulin sensitivity; insulin signaling; knock-down; loss of function; monocyte; nonalcoholic steatohepatitis; novel; obesogenic; paracrine; programs; receptor; response; sensor; success; wound healing

Summary This administrative supplement is in regard to Dr. Yuxiang Sun grant R01AG064869-01, titled “Nutrient- sensing GHS-R in macrophage reprogramming and inflamm-aging” (7/1/2019- 4/30/2024). During the funding period of this award, Dr. Sun's team has been very productive; they publish 7-8 peer-reviewed papers each year. They are the first to report the novel function of nutrient-sensing ghrelin signaling in inflamm-aging and demonstrate that ghrelin receptor GHS-R is a major metabolic regulator and immune sensor in aging and age- associated diseases (Aging Cell 2011; Aging 2014, Aging 2016, Adv Exp Med Biol. 2018, J of Gerontol. 2020, Aging 2021). A new manuscript from her lab regarding the generation and metabolic/immune characterization of myeloid-specific GHS-R knockout mice has been submitted to JCI. The results in this manuscript reveal that GHS-R, via an insulin signaling cascade, metabolically reprograms macrophage polarization to promote meta- inflammation. In addition, they have also made critical contributions to a Nature 2022 paper, which uncovers a novel effect of ghrelin in monocyte-associated wound repair. The exciting discovery of ghrelin signaling in aging immunity adds a new dimension to ghrelin biology (previously primarily known for energy metabolism), and have profound impact on both ghrelin and aging fields. Immunometabolism is a newly emerged frontier of biological research, relevant to vast physiological/pathological conditions. Their continued investigation of macrophage GHS-R in inflamm-aging and age-associated diseases will help to advance the understanding of aging immunity and to identify novel immunotherapeutic strategy to improve lifespan and healthspan. Dr. Sun's work is largely focused on immune cells such as macrophages, a high capacity flow cytometer is essential for immune cell studies. Due to institutional consolidation, the flow cytometer core has been re-located to a different campus 15-20 min drive away. In addition, the core service fee has become unsustainable, they are billed $3000-$4000/month. She did not budget core service fee in her original module budget because it was free before the relocation. The flow cytometer issue has posed a major setback for her team, and significantly hindered their efficiency and productivity. For the successful completion of the NIA R01 grant, Dr. Sun's team urgently needs a flow cytometer. Dr. Sun has obtained a favorable quote for a 4 laser 48 channel flow cytometer Cytek Aurora for $295,001. She is recently awarded an $150,000 equipment grant from AgriLife Research at Texas A&M University that can be used toward the flow cytometer. However, she still needs additional $145,001 for the purchase. Dr. Sun has consulted my PO, Dr. Mulualem Tilahun. Here she is submitting this administrative supplement application to seek NIA's support of $145,001. This critically needed equipment will have paramount impacts on the success of this project and her collaborators/colleagues, as well as the education and career advancement of her trainees.

概括 本行政补充是关于孙宇翔博士的授予 R01AG064869-01，标题为“营养- 在巨噬细胞重编程和炎症衰老中检测 GHS-R”（7/1/2019-4/30/2024）。在资助期间 此次获奖期间，孙博士团队成果丰硕；他们各自发表 7-8 篇同行评审论文 年。他们是第一个报告营养感应生长素释放肽信号在炎症衰老和 证明生长素释放肽受体 GHS-R 是衰老和年龄相关的主要代谢调节剂和免疫传感器 相关疾病（Aging Cell 2011；Aging 2014；Aging 2016；Adv Exp Med Biol.2018；J of Gerontol.2020； 老龄化 2021）。她的实验室关于生成和代谢/免疫特征的新手稿 骨髓特异性 GHS-R 敲除小鼠的样本已提交给 JCI。本手稿中的结果表明 GHS-R 通过胰岛素信号级联，代谢重新编程巨噬细胞极化，以促进元- 炎。此外，他们还为 Nature 2022 论文做出了重要贡献，该论文揭示了 胃饥饿素在单核细胞相关伤口修复中的新作用。饥饿素信号在衰老过程中的令人兴奋的发现 免疫为生长素释放肽生物学（以前主要以能量代谢而闻名）增加了一个新的维度，并且具有 对 ghrelin 和衰老领域产生了深远的影响。免疫代谢是生物学的一个新兴领域 与广泛的生理/病理条件相关的研究。他们继续研究巨噬细胞 GHS-R 在炎症衰老和年龄相关疾病中的作用将有助于增进对衰老的理解 免疫并确定新的免疫治疗策略以延长寿命和健康寿命。 孙博士的工作主要集中在免疫细胞，例如巨噬细胞，一种高容量流动的细胞 细胞仪对于免疫细胞研究至关重要。由于机构整合，流式细胞仪核心已 已搬迁至 15-20 分钟车程外的另一个校区。此外，核心服务费已成为 不可持续，他们每月的费用为 3000-4000 美元。她没有在原来的模块中预算核心服务费用 预算，因为搬迁前是免费的。流式细胞仪问题造成重大挫折 对于她的团队来说，并极大地阻碍了他们的效率和生产力。为了顺利完成 由于NIA R01资助，孙博士的团队急需一台流式细胞仪。孙博士获得好评 4 激光 48 通道流式细胞仪 Cytek Aurora 的报价为 295,001 美元。她最近被授予 德克萨斯农工大学农业生命研究中心提供 150,000 美元的设备补助金，可用于 流式细胞仪。然而，她还需要额外 145,001 美元来购买。 孙医生咨询了我的 PO，Mulualem Tilahun 博士。她在这里提交这份行政文件 补充申请以寻求 NIA 的 145,001 美元支持。这种急需的设备将具有 对这个项目及其合作者/同事以及教育的成功有着至关重要的影响 以及学员的职业发展。