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.

总结 本行政补充文件涉及孙宇翔博士授予的R 01 AG 064869 -01，标题为“营养- 在巨噬细胞重编程和炎症老化中感测GHS-R”（7/1/2019- 4/30/2024）。在融资期间 在此期间，孙博士的团队一直非常富有成效，他们发表了7-8篇同行评审的论文 年他们是第一个报道营养感应ghrelin信号在炎症-衰老中的新功能， 证明生长激素释放肽受体GHS-R是衰老和衰老过程中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, 老化2021年）。她实验室的一份新手稿，内容是关于 骨髓特异性GHS-R敲除小鼠的研究已提交给JCI。这份手稿的结果显示， GHS-R，通过胰岛素信号级联，代谢重编程巨噬细胞极化，以促进Meta- 炎症此外，他们还为Nature 2022论文做出了重要贡献，该论文揭示了一种 Ghrelin在单核细胞相关伤口修复中的新作用。令人兴奋的发现饥饿素信号在衰老 免疫为生长激素释放肽生物学（以前主要为能量代谢所知）增加了新的维度， 对胃饥饿素和衰老领域都有深远的影响。免疫代谢是生物学研究的一个新的前沿领域 研究，涉及广泛的生理/病理条件。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加深对衰老的认识 免疫和确定新的免疫策略，以提高寿命和健康寿命。 孙博士的工作主要集中在免疫细胞，如巨噬细胞，一个高容量的流动 血细胞计数器是免疫细胞研究必不可少的。由于机构整合，流式细胞仪核心 被重新安置到一个不同的校园15-20分钟的车程。此外，核心服务费也成为 不可持续的，他们每月收费3000 - 4000美元。她在最初的模块中没有预算核心服务费 因为在搬迁之前是免费的。流式细胞仪的问题造成了一个重大挫折 严重影响了他们的效率和生产力。为圆满完成 在NIA R 01的资助下，孙博士的团队急需一台流式细胞仪。孙博士获得了一个有利的 4激光48通道流式细胞仪Cytek Aurora报价为295，001美元。她最近被授予 德克萨斯A&M大学农业生命研究中心提供的15万美元设备赠款可用于 流式细胞仪然而，她仍然需要额外的145,001美元购买。 孙博士咨询了我的PO Mulualem Tilahun博士。在这里，她提交了这份行政 补充申请，以寻求NIA的145，001美元的支持。这些急需的设备将有 最重要的影响，这个项目的成功和她的合作者/同事，以及教育 和她的学员的职业发展