Molecular, Cellular, and Tissue Characterization Unit

分子、细胞和组织表征单元

基本信息

批准号：
10249192
负责人：
Dana Pe'er
金额：
$ 100.84万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-30 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10249192
关键词：
Address Anatomy Antibodies Atlases Autopsy Biology Biopsy Calibration Cells Cessation of life Clinical Complex Copy Number Polymorphism DNA Data Development Disseminated Malignant Neoplasm Dissociation Distant Metastasis Emerging Technologies Event Excision Freezing Gene Expression Profiling Generations Genomics Goals Growth Histology Human Human body Image Imaging technology Immune system Immunity Knowledge Lesion Link Liver Lung Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of pancreas Maps Metastatic Neoplasm to the Central Nervous System Metastatic malignant neoplasm to brain Metastatic to Molecular Neoplasm Metastasis Pancreas Patients Peritoneum Phylogeny Primary Neoplasm Process Production Proteins Protocols documentation RNA Resolution Sampling Site Small Nuclear RNA Source Structure Taxonomy Technical Expertise Technology Tissue Sample Tissues X-Ray Computed Tomography base cancer cell cell type cost effective insight multiple omics programs single cell technology single-cell RNA sequencing standard of care temporal measurement therapeutic target tumor tumor microenvironment

项目摘要

PROJECT SUMMARY (Characterization Unit) Metastasis involves the complex process of spreading of cancer cells beyond the primary tumor site, and is the cause of the majority of cancer deaths. The complexity arises from a dynamic interplay between heterogeneous and evolving cancer cells and the tumor microenvironment, during the progression from locally invasive to metastatic cancer. Understanding this progression, which is closely linked to immunity and development, calls for characterization of the various cell states and their interaction with the local niche during the progression. However, constructing such an atlas of the cellular states poses challenges due to the lack of a priori knowledge of all cell types present, the range of cell states to expect, or the rates of transition. To overcome these challenges we propose three iterative aims. First, we will establish a robust, cost-effective, high quality pipeline for single-cell genomics (primarily RNA) characterization of clinical samples provided by the Biospecimen Unit. Through this effort we will build a taxonomy of cell types, cell states and temporal lineage tracing connecting clones from the primary tumor to metastasis. Next, we will establish a robust, cost- effective, high quality pipeline for spatial mapping at single-cell resolution of clinical samples provided by the Biospecimen Unit with the goal systematically mapping the spatial structure of tumors/metastasis and their associated microenvironment. Finally, we will evaluate and assimilate the best new emerging technologies as these reach production level capacity. This is important to do as the field of single-cell technologies is moving forward at a staggering pace, thus poising the characterization unit will remain up to date on these technologies.

项目摘要（表征单元）转移涉及癌细胞扩散到原发肿瘤部位以外的复杂过程，并且是大多数癌症死亡的原因。复杂性源自动态相互作用在异质和进化的癌细胞和肿瘤微环境之间，从局部侵袭性癌症进展为转移性癌症。理解这一进展，即与免疫和发育密切相关，需要对各种细胞状态进行表征，并他们在发展过程中与当地利基的互动。然而，构建这样一个地图集由于缺乏对存在的所有细胞类型的先验知识，细胞状态提出了挑战预期的细胞状态范围或转变速率。为了克服这些挑战，我们建议三个迭代目标。首先，我们将建立一个强大的、具有成本效益的、高质量的单细胞管道生物样本单位提供的临床样本的基因组学（主要是 RNA）表征。通过这项努力，我们将建立细胞类型、细胞状态和时间谱系追踪的分类法将原发肿瘤的克隆与转移瘤连接起来。接下来，我们将建立一个稳健的、成本低廉的提供有效、高质量的临床样本单细胞分辨率空间绘图流程由生物样本单位负责，其目标是系统地绘制生物样本的空间结构肿瘤/转移及其相关的微环境。最后，我们将评估并吸收最佳新兴技术，因为这些技术达到了生产水平。这很重要，因为单细胞技术领域正以惊人的速度向前发展，从而为表征单元将保持这些技术的最新状态。