TOOLKIT Core

工具包核心

基本信息

批准号：
10706501
负责人：
CALVIN J KUO
金额：
$ 8.39万
依托单位：
STANFORD 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：
2021-09-21 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10706501
关键词：
3-Dimensional Address Air Anti-CD47 Area Automobile Driving Biological Biological Assay Brain Brain Neoplasms CRISPR library CRISPR screen CRISPR/Cas technology Cancer Model Cause of Death Cells Clustered Regularly Interspaced Short Palindromic Repeats Communication Development Disease Engineering Epithelial Cells Epithelium Genetic Genetic Screening Genomics Goals Human Immune In Vitro Information Dissemination Interruption Invaded Investigation Knock-out Libraries Life Liquid substance Lymphoid Malignant Neoplasms Mass Spectrum Analysis Metastatic malignant neoplasm to brain Microglia Modeling Molecular Molecular Profiling Mus Neoplasm Metastasis Neuroimmune Occupational activity of managing finances Organism Organoids Pathway interactions Patients Pattern Peptides Phagocytes Physiological Play Positron-Emission Tomography Post-Translational Protein Processing Production Proliferating Protein Analysis Protein Glycosylation Proteome Proteomics Qualifying Research Resources Sampling Scientist Signal Transduction Study models Survival Rate T-Lymphocyte Techniques Technology Therapeutic Tissue Banks Tissues Tumor-Associated Process Vision brain tissue candidate identification cell motility cytokine empowerment experience experimental study functional genomics glycoproteomics glycosylation improved in vitro Model induced pluripotent stem cell innovation insight migration neoplastic cell neuropathology new technology next generation novel preservation radiation response reconstitution response synergism tool transcriptomics tumor tumor-immune system interactions vaccine development vaccine strategy

项目摘要

PROJECT SUMMARY – TOOLKIT CORE The majority of cancer-related deaths are caused by metastatic disease, highlighting the glaring deficiency in our understanding of the processes of tumor dissemination. Research is substantially hampered by lack of physiologically-relevant tumor models and molecular tools necessary for discovering life-saving therapies. The Stanford Brain Metastasis Consortium (SBMC) is focused on identifying the genetic underpinnings regulating brain metastases, a disease with limited treatment options and meager survival rates. In support of this goal, the Toolkit Core provides innovative experimental solutions from leading experts in organoid modeling (Dr. Calvin Kuo), genomic functional screens (Dr. Michael Bassik), and glycoproteomics (Dr. Sharon Pitteri) to execute the projects proposed within the SBMC. The Toolkit Core team has diverse yet complementary areas of expertise and is qualified to specifically address the unmet needs outlined in this RFA: Metastasis Research Network by providing novel experimental organoid models, and cutting-edge CRISPR and proteomic tools for characterizing and manipulating the poorly understood signaling nodes driving brain metastatic disease. Specifically, the Kuo lab will provide patient and murine-derived brain metastatic 3D organoids to study radiation response in Project 1, explore the intricate crosstalk between metastatic epithelium and the immune microenvironment in Projects 1 and 2, and develop novel lymphoid organoids for modeling T-cell priming in Project 3. The Bassik lab will provide innovative CRISPR tools for targeted genetic screens in Project 1 to explore the interaction between tumor-associated microglia and metastatic epithelial cells, along with engineering iPSCs for Project 3 to develop vaccine strategies for brain metastasis. The Pitteri lab will provide proteomic analysis for Projects 1–3, to characterize glycosylation patterns and features in brain metastatic tissue and organoids, thus providing critical biological insights into metastatic disease. Together, these resources will empower the diverse investigations of the SBMC toward improved therapeutic approaches.

项目摘要 – 工具包核心大多数与癌症相关的死亡是由转移性疾病引起的，这凸显了癌症相关的明显缺陷我们对肿瘤传播过程的理解因缺乏相关知识而受到严重阻碍。发现挽救生命的疗法所必需的生理相关肿瘤模型和分子工具。斯坦福脑转移联盟 (SBMC) 致力于识别调节的遗传基础脑转移瘤是一种治疗选择有限且存活率很低的疾病。 Toolkit Core 提供来自类器官建模领域领先专家（Calvin 博士）的创新实验解决方案 Kuo）、基因组功能筛选（Michael Bassik 博士）和糖蛋白组学（Sharon Pitteri 博士）执行 SBMC 内提议的项目。 Toolkit 核心团队拥有多元化但互补的专业领域，有资格专门解决本 RFA 中概述的未满足需求：转移研究网络通过提供新型实验类器官模型，以及用于表征和操纵不良分子的尖端 CRISPR 和蛋白质组学工具具体而言，郭实验室将为患者和患者提供了解驱动脑转移疾病的信号节点。鼠源性脑转移性 3D 类器官研究项目 1 中的辐射反应，探索复杂的项目 1 和 2 中转移性上皮与免疫微环境之间的串扰，并开发项目 3 中用于模拟 T 细胞启动的新型淋巴类器官。Bassik 实验室将提供创新的项目 1 中用于靶向遗传筛选的 CRISPR 工具，探索肿瘤相关基因之间的相互作用小胶质细胞和转移性上皮细胞，以及项目 3 的 iPSC 工程，以开发疫苗策略 Pitteri 实验室将为项目 1-3 提供蛋白质组学分析，以表征脑转移组织和类器官中的糖基化模式和特征，从而提供关键的生物学这些资源共同将为 SBMC 的多样化研究提供支持。寻求改进的治疗方法。