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 这种行政补充是关于Yuxiang Sun博士赠款R01AG064869-01，标题为“ Nutrient- 在巨噬细胞重编程和炎症时感应GHS-R”（7/1/2019-4/30/2024）。在资金期间 这个奖项的期限，Sun博士的团队非常有生产力。他们发表7-8个同行评审的论文 年。它们是第一个报告炎症和炎症和 证明生长素蛋白受体GHS-R是衰老和年龄的主要代谢调节剂和免疫传感器 相关疾病（衰老细胞2011； 2014年老化，2016年老化，Adv MedBiol。2018，Gerontol，Gerontol。2020， 衰老2021）。她的实验室的新手稿，涉及一代和代谢/免疫特征 骨髓特异性的GHS-R敲除小鼠已提交给JCI。此手稿的结果表明 GHS-R通过胰岛素信号级联反应，代谢重新编程巨噬细胞极化，以促进元 此外，他们还为2022年的大自然做出了重要贡献，该论文发现了 生长素蛋白在单核细胞相关的伤口修复中的新作用。衰老中生长素释放信号的令人兴奋的发现 免疫力为生生物学生物学（以前主要以能量代谢而闻名）增加了一个新维度，并且具有 对生长素和衰老场的深刻影响。免疫代谢是新出现的生物学领域 研究，与庞大的身体/病理状况有关。他们继续投资巨噬细胞 GHS-R在炎症和年龄相关的疾病中将有助于提高对衰老的理解 免疫并确定新的免疫治疗策略，以改善寿命和健康状态。 Sun博士的工作主要集中在巨噬细胞等免疫细胞上，高容量流量 细胞仪对于免疫细胞研究至关重要。由于机构合并，流式细胞仪芯具有 我们被重新安置到15-20分钟车程的不同校园。此外，核心服务费已成为 不可持续的，他们的收费为$ 3000- $ 4000/月。她的原始模块没有预算核心服务费 预算是因为它在搬迁之前是免费的。流式细胞仪问题已被定位为重大挫折 对于她的团队，并极大地阻碍了他们的效率和生产力。成功完成 在NIA R01 Grant中，Sun博士的团队急需流式细胞仪。太阳博士获得了有利的 48激光48通道流式细胞仪Cytek Aurora的报价价格为295,001美元。她最近被授予 得克萨斯州A＆M大学的Agrilife Research的15万美元设备赠款，可用于 流式细胞仪。但是，她仍然需要额外的145,001美元才能购买。 Sun博士咨询了我的PO Mulualem Tilahun博士。她在这里提交此行政 补充申请，以寻求NIA的支持145,001美元。这种迫切需要的设备将有 派拉蒙影响该项目的成功及其合作者/同事以及教育 以及她的学员的职业发展。