Multi-omic Evaluation of the mTOR pathway in Radiotherapy-Related Fatigue

mTOR 通路在放射治疗相关疲劳中的多组学评估

• 批准号: 10665092
• 负责人: Velda Janet Gonzalez-Mercado
• 金额: $ 16.71万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10665092
• 关键词: 70-kDa Ribosomal Protein S6 Kinases; Acute; Address; Area; Bioinformatics; Biological; Biological Assay; Biological Process; Blood specimen; Cancer Patient; Candidate Disease Gene; Clinical Data; Collaborations; Complex; DNA Methylation; DNA methylation profiling; Data; Development; Distress; Enzyme-Linked Immunosorbent Assay; Etiology; Evaluation; Event; Expenditure; FRAP1 gene; Fatigue; Gene Expression; Genes; Genetic; Genetic Markers; Genomics; Goals; Grant; Homeostasis; Incidence; Inflammation; Intervention; Journals; Knowledge; Literature; Malignant Neoplasms; Malignant neoplasm of prostate; Mentors; Mentorship; Methods; Mitochondria; Modeling; Molecular; Molecular Target; Oxidative Stress; Pathway interactions; Patients; Peer Review; Performance; Phenotype; Phosphorylation; Plasma; Population; Postdoctoral Fellow; Productivity; Prostate Cancer therapy; Proteins; Proto-Oncogene Proteins c-akt; Publications; Radiation therapy; Regimen; Reporting; Research; Research Personnel; Research Proposals; Sampling; Science; Scientist; Series; Sirolimus; Strategic Planning; Symptoms; System; TSC1 gene; TSC1/2 gene; Training; United States National Institutes of Health; Whole Blood; Work; Writing; adenylate kinase; biobehavior; cancer therapy; care episode; career; cell growth; clinically significant; design; differential expression; disabling symptom; economic implication; effective intervention; effective therapy; energy balance; epigenetic marker; epigenetic regulation; epigenomics; experience; improved; innovation; laboratory experience; mTOR Signaling Pathway; men; mitochondrial dysfunction; mortality; multiple omics; novel; patient oriented research; personalized medicine; prevent; prognostic; prostate radiotherapy; protein expression; radiation response; side effect; skills; symptom management; symptom science; therapeutic target; transcriptome sequencing; transcriptomics

PROJECT SUMMARY/ABSTRACT Cancer-related fatigue is one of the most debilitating, distressing, and commonly reported side effects of cancer treatment, with up to 71% of prostate cancer (PC) patients complaining of fatigue during radiation therapy (RT). While the etiology and associated mechanisms of the fatigue responses to RT treatment remain elusive, the candidate recently found evidence that changes in gene expression of both MTOR and p70S6K were associated with changes in fatigue during RT. The proposed study will explore the network of interactions among the biomolecules present in mTOR signaling pathways at the systems level, which could shift existing symptom management paradigm as it relates to fatigue by offering an understanding of how the mTOR biological functions are regulated and how the fatigue may emerge from its dysregulation. The proposed research is guided by a model of dysregulation of the mTOR pathway and RT-related fatigue. The training plan was designed to allow the candidate to build on her post-doctoral experience to receive the necessary training to become an independent investigator, proficient in genomics, other “omics”, and bioinformatics as they relate to symptom science. An experienced team of scientists will provide career mentoring and training with the following objectives: (1) enhance knowledge of “omics” (i.e., transcriptomics, epigenomics), and the science related to mechanisms of symptoms; (2) gain additional expertise in the characterization of fatigue phenotypes and in relation to patient biological and clinical data; (3) attain bioinformatics proficiency (via didactic coursework and comprehensive hands-on training) in the analysis of transcriptomic, epigenomic, and protein data, and interpretation of the findings; and (4) improve scientific writing skills and build collaborations with experts in the fields of bio-behavioral, symptom management, and omic research that will allow for successful publications in high-impact, peer-reviewed journals, and submission of competitive NIH R-Series grant. The training plan is for thirty-six months and includes six core areas: didactic; interdisciplinary seminars; mentorship; laboratory training; research; and dissemination. There are 3 specific aims proposed. Aim 1: Identify mTOR pathway and activity- related genes associated with changes in fatigue scores from pre, end, and 1 month after stereotactic body radiation therapy (SBRT) in a sample of men with PC. Aim 2: Investigate the relationships between epigenetic regulation of mTOR pathway genes associated with changes in fatigue scores from pre, end, and 1 month after SBRT in a sample of men with PC. Aim 3: Determine the associations between changes in mTOR signaling pathway and activity-related proteins with changes in fatigue scores from pre, end, and 1 month after SBRT in a sample of men with PC. This study identifies a novel area for exploration and aligns well with the NINR Strategic Plan calling for studies on symptom science with a focus on Promoting Personalized Medicine, by understanding the mechanisms underlying the symptom of fatigue through symptom science research.

项目总结/文摘

项目成果

Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study.

• DOI: 10.1155/2021/7967552
• 发表时间: 2021
• 期刊: Depression research and treatment
• 作者: Gonzalez-Mercado VJ;Lim J;Saligan LN;Perez N;Rodriguez C;Bernabe R;Ozorio S;Pedro E;Sepehri F;Aouizerat B
• 通讯作者: Aouizerat B