3D Whole-Pancreas Analysis of Mouse Models of Pancreatic Cancer

胰腺癌小鼠模型的 3D 全胰腺分析

基本信息

批准号：
10830513
负责人：
Denis Wirtz
金额：
$ 8.19万
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

项目摘要

Project Summary This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA- 23-045 and is a collaboration between the Cellular Cancer Biology Imaging Research (CCBIR) Program and the Pancreatic Ductal Adenocarcinoma Stroma Reprogramming Consortium (PSRC). Pancreatic cancer is a deadly disease with a dismal prognosis but arises from precancerous lesions that lack the ability to spread beyond the pancreas, underscoring the opportunity for cancer interception in this disease. Genetically engineered mouse models provide a key opportunity to study premalignant pancreatic tumorigenesis over time to provide a rational foundation for such interception approaches, as serial tissue samples from these time points are not available from human patients. However, tools to quantify precancer burden in mice at the single-cell level through the whole pancreas are currently lacking; such tools would greatly improve the rigor of evaluation of these models. As such, we will leverage our recently developed deep learning tool CODA for 3D reconstruction and cellular quantification, which is undergoing expanded application and validation as part of the CCBIR Program. Using CODA, we will analyze whole pancreata from the inducible KRAS (iKRAS) mouse model, which allows assessment of epithelial-microenvironment cross talk at multiple time points in early tumorigenesis, a key goal of the PSRC. This collaboration between the CCBIR Program and the PSRC will apply novel cancer imaging technologies to innovative mouse models of pancreatic cancer, providing important insights into the cellular alterations in early pancreatic tumorigenesis. These studies will also provide additional validation of the CODA pipeline and poise this approach for application more broadly across mouse models of cancer.

项目概要本申请是为了响应被识别为 NOT-CA- 的特殊利益通知 (NOSI) 而提交的 23-045 是细胞癌症生物学成像研究 (CCBIR) 计划和胰腺导管腺癌基质重编程联盟（PSRC）。胰腺癌是一种预后不佳的致命疾病，但由缺乏扩散能力的癌前病变引起超越胰腺，强调了在这种疾病中拦截癌症的机会。遗传上工程小鼠模型为研究癌前胰腺肿瘤随时间的变化提供了关键机会为此类拦截方法提供合理的基础，因为这些时间的连续组织样本人类患者无法获得积分。然而，量化小鼠癌前负担的工具目前缺乏整个胰腺的单细胞水平；这些工具将大大提高对这些模型的评估。因此，我们将利用我们最近开发的深度学习工具 CODA 进行 3D 重建和细胞定量，作为 CCBIR 计划。使用 CODA，我们将分析诱导型 KRAS (iKRAS) 小鼠的整个胰腺模型，允许在早期的多个时间点评估上皮微环境串扰肿瘤发生，PSRC 的一个关键目标。 CCBIR 计划和 PSRC 之间的合作将将新型癌症成像技术应用于胰腺癌的创新小鼠模型，提供重要的深入了解早期胰腺肿瘤发生中的细胞变化。这些研究还将提供额外的 CODA 流程的验证，并使该方法能够在小鼠模型中更广泛地应用癌症。