Cell free RNA liquid biopsies

无细胞 RNA 液体活检

• 批准号: 10363505
• 负责人: Roman Reggiardo
• 金额: $ 4.47万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10363505
• 关键词: Awareness; Biological; Biological Assay; Biology; Blood; Blood Cells; Blood specimen; Bone Marrow; Bone Marrow Aspiration; Bone marrow biopsy; COVID-19 patient; Cell Count; Cells; Classification; Clinical; Code; DNA Transposable Elements; Data; Data Set; Detection; Developmental Cell Biology; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Disease Marker; Doctor of Philosophy; Ensure; Environment; Event; Fibrosis; Generations; Genetic Transcription; Genomics; Genotype-Tissue Expression Project; Global Change; Goals; Growth; Health; Hematology; Hematopoiesis; Hematopoietic; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Hemorrhage; Human; In Vitro; Individual; Infection; Label; Lead; Lung Adenocarcinoma; Mentorship; Mesenchymal Stem Cells; Methylation; Monitor; National Institute of Diabetes and Digestive and Kidney Diseases; PET/CT scan; Pathology; Patients; Performance; Plasma; Population; Production; RNA; RNA analysis; RNA marker; Recovery; Research; Research Personnel; Sampling; Sedation procedure; Techniques; Testing; The Cancer Genome Atlas; Tissue Sample; Tissues; Training; Transcriptional Regulation; Untranslated RNA; Validation; Whole Blood; X-Ray Computed Tomography; base; bone marrow mesenchymal stem cell; cell free DNA; cell type; cohort; cost; diagnostic biomarker; extracellular; extracellular vesicles; leukemia/lymphoma; liquid biopsy; machine learning algorithm; member; pain relief; pancreatic cancer patients; peripheral blood; progenitor; programs; side effect; single-cell RNA sequencing; specific biomarkers; stem cell biology; stem cell population; success; tool; transcriptome sequencing; tumorigenesis

ABSTRACT The ultimate goal of this proposal is to verify an RNA liquid biopsy platform and transition it to have specific utility for the study, and non-invasive assessment, of the hematopoietic bone marrow (BM) niche. In addition to their reliance of material excreted from dying, diseased cells, cell-free DNA (cfDNA) platforms are limited to primarily detecting changes in somatic genomic sequence, copy number, or methylation status. Many biological and clinical events, such as hematopoiesis, fibrosis, and tumorigenesis, are executed via global changes in transcriptional regulation. My PhD advisor Dr. Daniel Kim and I have established a platform for exRNA liquid biopsy in human blood-plasma that has demonstrated significant diagnostic and monitoring potential in both Pancreatic cancer and COVID-19 patients. I propose to continue this research to complete my PhD by assessing diagnostic performance of the exRNA platform in a new cohort of 60 lung adenocarcinoma (LUAD) patients with matched controls. Furthermore, I will apply my expertise in exRNA liquid biopsies to assay the transcriptional dynamics of hematopoiesis and hematopoietic stem cells (HSCs) in the bone marrow (BM) niche. Currently, bone marrow biopsies or aspirations are used to determine bone marrow health and production. These techniques are costly and require sedation and/or pain relief for the subject and have the potential to lead to long term discomfort, infection, excessive bleeding, and other side-effects. BM aspirations remain a critical diagnostic and monitoring tool for HSC transplant recovery, leukemias and lymphomas, blood cell pathologies, and infections of unknown origin but the primary readout remains identification and counting of cell types. I hypothesize that hematopoietic lineages within the BM secrete exRNA that reflect cell state and identity that can be used in a non-invasive RNA liquid biopsy for detailed study of transcription and populations within the BM. I propose to identify exRNA expressed and secreted by HSCs and the remaining hematopoietic lineage in order to develop a platform to deconvolute peripheral blood into constituent hematopoietic cell types without the need for HSC mobilization.

摘要