Assessing if tumor induced muscle cachexia is initiated by defects in Myosin Heavy Chain production and localization in a Drosophila tumor model

评估果蝇肿瘤模型中肿瘤诱发的肌肉恶病质是否是由肌球蛋白重链产生和定位缺陷引发的

• 批准号: 10715061
• 负责人: Mardelle Renee Atkins
• 金额: $ 16.99万
• 依托单位: SAM HOUSTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10715061
• 关键词: Affect; Automobile Driving; Basic Science; Body Weight; Body part; Cachexia; Cancer Etiology; Cancer Model; Cancer Patient; Cells; Cellular Stress; Cessation of life; Chronic; Clinic; Clinical; Communities; Complex; Coupled; Data; Defect; Development; Diagnosis; Diagnostic; Dietary Intervention; Disease; Distant; Drosophila genus; Early Diagnosis; Endocrine; Ethics; Event; Family member; Fatty acid glycerol esters; Foundations; Future; Genetic; Goals; Image; Immune System Diseases; Intervention; Laboratories; Larva; Learning; Malignant Neoplasms; Master of Science; Metabolic; Microtubules; Modeling; Molecular Chaperones; Mus; Muscle; Muscle Fibers; Muscle Weakness; Muscular Atrophy; Myosin ATPase; Myosin Heavy Chains; Myosin Light Chains; Names; Nuclear; Organ; Outcome; Pathology; Pathway interactions; Patients; Phenotype; Process; Production; Publishing; Quality of life; Refractory; Research; Research Personnel; Resolution; Sarcomeres; Signal Pathway; Speed; Stains; Stereotyping; Stress; Students; Syndrome; System; Systemic disease; Testing; Time; Tissues; Training; Work; cancer cachexia; carcinogenesis; cost; genetic approach; genetic manipulation; in vivo; insight; mouse model; novel; prevent; programs; protein folding; protein transport; psychologic; response; skeletal muscle wasting; tool; transcriptomics; tumor; undergraduate student; wasting

PI: Mardelle Atkins Commons ID: MRATKINS Abstract: Assessing if tumor induced muscle cachexia is initiated by defects in Myosin Heavy Chain production and localization in a Drosophila tumor model Cachexia is a devastating cancer associated disease which affects millions each year and yet is untreatable. Currently cachexia is defined in patients by rapid loss of >5% of body weight with muscle weakness and an underlying chronic condition. Cachexia is considered a late stage consequence of cancer. Here, we present preliminary data acquired by undergraduate students using a Drosophila model of cancer cachexia. Excitingly, we have identified stereotyped changes which occur in vivo early in tumor development. In this study we will distinguish the origins of these phenotypes, assess their contribution to cachexia progression, and investigate if the Hippo signaling pathway is regulating early or late events in cachexia.We will leverage our expertise in staining and imaging as well as new community tools which allow tissue specific genetic manipulation to achieve our goals. These works, conducted by underrepresented undergraduate researchers and master’s students will shed light on the unknown etiology of cancer induced cachexia. Results of these, and future translational works, are the foundation to developing earlier diagnostics permitting interventions to prevent cachexic progression in patients. Through the course of this support the PI will establish an independent research program which will illuminate the earliest steps of cachexic changes in muscles and provide critical training and support to underrepresented trainees.

PI：Mardelle阿特金斯 Commons ID： 翻译后摘要：评估肿瘤引起的肌肉恶病质是否是由肌球蛋白缺陷引发的 果蝇肿瘤模型中重链的产生和定位 恶病质是一种毁灭性的癌症相关疾病，每年影响数百万人 但却无法治愈目前，恶病质在患者中定义为>5%的 体重与肌肉无力和潜在的慢性疾病。恶病质是 被认为是癌症的晚期后果。在这里，我们提供了初步数据， 由本科生使用果蝇癌症恶病质模型获得。 令人兴奋的是，我们已经确定了在体内肿瘤早期发生的定型变化， 发展在这项研究中，我们将区分这些表型的起源，评估 它们对恶病质进展的贡献，并研究Hippo信号传导是否 通路调节恶病质的早期或晚期事件。我们将利用我们的专业知识， 染色和成像以及新的社区工具， 操纵来实现我们的目标。这些作品，由代表性不足的 本科研究人员和硕士生将揭示未知的 癌症诱发恶病质的病因学。这些结果，以及未来的翻译作品， 是开发早期诊断的基础， 患者恶病质进展。通过这一支持过程，PI将建立 一个独立的研究项目，将阐明恶病质的最早阶段， 肌肉的变化，并提供关键的训练和支持， 实习生