权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Predoctoral to Postdoctoral Research Training in ctDNA Biology for Liquid Biopsy of Cancer

癌症液体活检 ctDNA 生物学博士前至博士后研究培训

基本信息

批准号：
10305558
负责人：
Jordan C Cheng
金额：
$ 4.2万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10305558
关键词：
Address Animals Apoptosis Axilla Bioinformatics Biological Biological Markers Biological Models Biology Blood Circulation CRISPR/Cas technology Cancer Center Cancer Detection Cancer Patient Cell Culture Techniques Cerebrospinal Fluid Clinical Complex Comprehensive Cancer Center DNA DNA purification DNA sequencing Data Detection Development Disease Progression Disseminated Malignant Neoplasm Doctor of Philosophy Early Diagnosis Elements Epidermal Growth Factor Receptor Excision Exclusion Genetic Genomics Genotype Goals Head and neck structure Inflammatory Response Institutes Jordan Lead Length Leukocytes Libraries Machine Learning Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of lung Malignant neoplasm of pancreas Measurement Mentorship Methodology Methods Methylation Modeling Modernization Monitor Mutate Mutation Nature Non-Small-Cell Lung Carcinoma Oncogenic Oncology Oral Organoids Outcome Patients Pharmacotherapy Phase Plasma Population Positioning Attribute Postdoctoral Fellow Preparation Process Protocols documentation Regulatory Pathway Research Research Project Grants Research Training Sampling School Dentistry Screening for cancer Selection Bias Testing Therapeutic Tissues Training Urine Validation Work anticancer research base cancer cell cancer genetics cancer type career cell free DNA cohort deep sequencing design ds-DNA electric field experimental study extracellular improved insight interest liquid biopsy methylation pattern mutant next generation sequencing novel pre-doctoral professor saliva sample skills tumor tumor DNA tumor progression

项目摘要

PROJECT SUMMARY/ABSTRACT Circulating tumor DNA (ctDNA) which mirrors the parental tumor, is present in the plasma of non-small cell lung carcinoma (NSCLC) patients. Liquid biopsy analysis of ctDNA allows early detection and genetic monitoring. However, current PCR-based liquid biopsy methods often have difficulty detecting ctDNA due to low copies in circulation. In contrast, the electric field-induced release and measurement liquid biopsy (eLB) platform, detects mutant EGFR (L858R, exon19del, T790M) ctDNA with a >90% tissue-genotype concordance in <50ul of unprocessed plasma of NSCLC patients. Preliminary data demonstrate that the ctDNA detected by eLB may be ultrashort single-stranded ctDNA (usssctDNA) which contrasts the typically described 160-basepair internucleosomal double-stranded ctDNA. This new subpopulation is undetectable through PCR-based liquid biopsy methods due to size-selection bias. The goal of the F99 Phase is to use usssctDNA-seq, a novel NGS pipeline, to explore if NSCLC plasma contains high quantities of ctDNA that are ultrashort and single-stranded. This pipeline consists of a usssctDNA-specific extraction, library preparation, deep sequencing, and bioinformatic analysis. To verify, 80 late-stage NSCLC EGFR-mutated plasma samples will undergo usssctDNA-seq. The discovery of usssctDNA will open up a wealth of previously unnoticed information leading to improved treatment and survival of NSCLC patients. Afterward, during the K00 Phase, the trainee hopes to explore the biological origins of biofluid ctDNA and the incorporation of usssctDNA into modern multi-analyte approaches for pan- cancer detection. This will involve training in new skills such as organoid modeling, methylation and leukocyte sequencing, and bioinformatic machine learning at a world-leading cancer-oriented institute. Ultimately, the goal of this proposed F99/K00 project will to prepare the trainee for a career in cancer research with an expertise in liquid biopsy and cell-free DNA biology.

项目总结/文摘