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RTB 1

实时TB 1

基本信息

批准号：
10375194
负责人：
Laura DeLong Wood
金额：
$ 37.77万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2021-12-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10375194
关键词：
3-Dimensional Antibodies Area Automobile Driving Beds Biological Cells Cellular Assay Cellular biology Clinical Cohort Studies Collaborations Complex Cytometry Development Disease Distant Metastasis Epithelial Event Fibroblasts Foundations Frequencies Gene Expression Goals Human Image Imaging technology Immune Inflammatory Invaded Label Liver Malignant - descriptor Malignant Neoplasms Malignant neoplasm of pancreas Maps Mesenchymal Molecular Molecular Analysis Morphology Neoplasm Metastasis Pancreas Pancreatic Ductal Adenocarcinoma Performance Population Primary Neoplasm Process Prognosis Proteomics Research Resolution Sampling Stromal Cells Structure Techniques Testing Three-Dimensional Imaging Tissue Model Tissue Sample Tissues Validation Veins Venous Work cancer cell cancer imaging cell type deep learning high dimensionality human tissue imaging platform improved insight multi-scale modeling multiple omics new therapeutic target novel novel strategies pancreatic ductal adenocarcinoma cell pancreatic neoplasm pancreatic tumorigenesis prevent programs reconstruction synergism technology development tool transcriptome transcriptomics tumor microenvironment

项目摘要

Project Summary Pancreatic cancer is a deadly disease with a dismal prognosis and a high frequency of distant metastasis. One likely reason for the frequent metastases in pancreatic cancer is the ability of malignant cells in the primary tumor to invade veins, providing direct access to the liver. While this intravasation is a key first step in metastasis, little is known about the molecular and cellular alterations that underlie this process. Foci of cancer cell intravasation are small and complex, requiring high-resolution three-dimensional (3D) approaches to study them. In this Research Test Bed of our Center for 3D Multiscale Cancer Imaging, we will comprehensively characterize the morphological, cellular, and molecular alterations of foci of intravasation in 3D in human pancreatic cancer samples. In collaboration with Technology Development Unit 1, we will employ our novel deep learning 3D reconstruction approach CODA to serially sectioned pancreatic cancer samples with venous invasion to quantify morphological and cellular features of intravasation. We will also perform multi-dimensional immune profiling of these intravasation foci in 3D using imaging mass cytometry, which can label with 40 antibodies on each tissue section. These analyses will allow us to compare the tumor microenvironment in foci of intravasation to that in other areas of cancer and in uninvolved veins. In collaboration with Technology Development Unit 2, we will analyze the gene expression changes in these intravasation foci by applying a newly developed spatial transcriptomics/proteomics approach (DBit-Seq) to pancreatic cancer samples previously reconstructed by CODA. This approach will provide the first 3D multi-scale models of venous invasion in human pancreatic cancer, providing unprecedented morphological, cellular, and molecular detail of the process of intravasation and initiation of metastasis. In addition, our Research Test Bed will provide a critical opportunity to implement, validate, and iteratively improve the novel approaches from the two Technology Development Centers. We will work closely with these Technology Development Centers in order to evaluate the performance of CODA and DBit-Seq in our human pancreatic tissue samples, allowing validation of the cell type identification and molecular alterations by complementary techniques. The studies in our Research Test Bed will promote significant improvement of the CODA and DBit-Seq imaging platforms while also providing important biological insights into the initiation of metastasis in pancreatic cancer.

项目总结