Transfer RNA sequencing and application to cancer research and clinics

将 RNA 测序和应用转移到癌症研究和临床

基本信息

批准号：
10705187
负责人：
Bruce Marc Bissonnette
金额：
$ 39.72万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-15 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10705187
关键词：
Address Bacteria Biological Biological Markers Biological Models Biology Biopsy Specimen Blood Blood specimen Cancer Biology Cancer Diagnostics Cancer Etiology Cancer Patient Categories Cells Cessation of life Chemotherapy-Oncologic Procedure Clinic Clinical Colorectal Cancer Colorectal Neoplasms Colorectal Surgery Complex DNA Data Detection Development Diagnostic Neoplasm Staging Dimensions Disease Environment Essential Genes Excision Family Feasibility Studies Feces Formalin Gene Expression Genes Genetic Code Genomics Growth High-Throughput Nucleotide Sequencing Higher Order Chromatin Structure Human Intestines Laboratories Legal patent Malignant - descriptor Malignant Neoplasms Manuscripts Measures Metadata Methods Microbe Modification Morbidity - disease rate Neoplasm Metastasis Normal tissue morphology Operative Surgical Procedures Pathogenesis Patient Care Patient-Focused Outcomes Patients Pattern Performance Perioperative Physicians Physiology Play Postoperative Period Prognosis Property Protein Biosynthesis Proteins RNA Recurrence Recurrent Malignant Neoplasm Regulation Reproducibility Resources Risk Risk Assessment Role Sampling Small RNA Source Stimulus Technology Testing Therapeutic Time Tissue Sample Toxic effect Transfer RNA Transfer RNA Aminoacylation Treatment outcome Tumor Biology Tumor Tissue aggressive therapy anticancer research biobank biomarker discovery cancer biomarkers cancer care cancer recurrence cancer risk cancer surgery cancer therapy cell type chemotherapy clinical application clinical care colon cancer patients epigenomics epitranscriptomics gut bacteria gut microbes gut microbiota high risk host microbiome host-microbe interactions human disease improved lens liquid biopsy mRNA Translation microbial mortality mouse model new technology novel precision medicine prevent prognostic response stool sample tissue fixing transcriptome transcriptome sequencing tumor

项目摘要

Project Abstract Most effective tumor treatments target multiple cellular mechanisms. This proposal will explore a previously under-appreciated cellular mechanism in cancer biology using a newly developed high throughput sequencing technology. Transfer RNAs (tRNAs) are adaptor molecules that read the genetic code for protein biosynthesis. tRNAs are essential for gene expression, an emerging source of cancer-related biomarkers, and a treasure trove of epitranscriptomic marks from both human and disease-associated microbes. tRNAs are dysregulated in many cancers. Due to technical difficulties, tRNA biology and its implications in clinical cancer care have lagged far behind other DNA and RNA-based approaches. We recently developed a new technology called Multiplex Small RNA-seq (MSR-seq) which makes feasible for the first time clinical-scale tRNA studies. Specific Aim 1 will further expand the capability and scope of MSR-seq for clinical samples. Colorectal cancer (CRC) is the second leading cause of cancer-related death in the US. Chemotherapy regimens have not substantively changed in a decade, are unnecessary for 50% of patients, and ineffective in another 30%. Currently there is no way to categorize patients ahead of time. Recent studies provide evidence that gut bacteria can influence growth and metastasis of colorectal tumors. Interactions between tumors and commensal gut microbes provide a new lens to understand the biology of CRC and a new opportunity to identify patients at risk for cancer recurrence and patients who have no need to endure chemotherapy. Specific Aim 2 will apply MSR- seq to screen a biobank of blood, biopsy, and stool samples from CRC patients, and to study a murine model of CRC recurrence. This combination of a unique biobank with a new technology has potential to transform how CRC is treated and explores the complex host-microbe interactions in a human disease.

项目摘要最有效的肿瘤治疗针对多种细胞机制。该提案将探讨使用新开发的高通量研究以前在癌症生物学中未被充分认识的细胞机制测序技术。转移 RNA (tRNA) 是读取蛋白质遗传密码的衔接分子生物合成。 tRNA 对于基因表达至关重要，是癌症相关生物标志物的新兴来源，并且来自人类和疾病相关微生物的表观转录组标记的宝库。 tRNA 是在许多癌症中失调。由于技术困难，tRNA生物学及其对临床癌症的影响护理远远落后于其他基于 DNA 和 RNA 的方法。我们最近开发了一项新技术称为多重小 RNA 序列 (MSR-seq)，这使得首次临床规模的 tRNA 研究变得可行。具体目标 1 将进一步扩大 MSR-seq 用于临床样本的能力和范围。结直肠癌 (CRC) 是美国癌症相关死亡的第二大原因。化疗方案尚未十年内发生了实质性改变，对 50% 的患者来说是不必要的，对另外 30% 的患者来说是无效的。目前还没有办法提前对患者进行分类。最近的研究提供证据表明肠道细菌可以影响结直肠肿瘤的生长和转移。肿瘤与共生肠道之间的相互作用微生物为了解结直肠癌的生物学提供了新的视角，并为识别高危患者提供了新的机会适用于癌症复发及无需忍受化疗的患者。具体目标 2 将应用 MSR- seq 筛选 CRC 患者的血液、活检和粪便样本的生物库，并研究小鼠模型结直肠癌复发。独特的生物样本库与新技术的结合有可能改变 CRC 被治疗并探索人类疾病中复杂的宿主-微生物相互作用。