TOOLKIT Core

工具包核心

• 批准号: 10272362
• 负责人: CALVIN J KUO
• 金额: $ 14.37万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-21 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10272362
• 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; Custom; Development; Disease; Engineering; Epithelial; Epithelial Cells; Genetic; Genetic Screening; Genomics; Glare; Goals; Human; Immune; In Vitro; Information Dissemination; Interruption; 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; Protein Analysis; Protein Glycosylation; Proteome; Proteomics; Research; Resources; Sampling; Savings; Scientist; Signal Transduction; Study models; Survival Rate; T-Lymphocyte; Techniques; Technology; Therapeutic; Tissue Banks; Tissues; Tumor-Associated Process; Vaccines; Vision; base; brain tissue; cell motility; cytokine; 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

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.

项目总结-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，这突出了癌症治疗的明显不足。 我们对肿瘤扩散过程的理解。研究工作因缺乏 生理学相关的肿瘤模型和发现拯救生命疗法所必需的分子工具。的 斯坦福大学脑转移联盟（SBMC）专注于确定调节肿瘤转移的遗传基础。 脑转移，一种治疗选择有限且生存率极低的疾病。为了实现这一目标， Toolkit Core提供来自类器官建模领域领先专家的创新实验解决方案（卡尔文博士 Kuo）、基因组功能筛选（Michael Bassik博士）和糖蛋白组学（Sharon Pitteri博士）来执行 在SBMC内提出的项目。 工具包核心小组拥有多种但互补的专门知识领域，有资格具体处理 通过提供新的实验类器官，满足RFA中概述的未满足的需求：转移研究网络 模型，以及尖端的CRISPR和蛋白质组学工具，用于表征和操纵 了解驱动脑转移性疾病的信号节点。具体来说，Kuo实验室将为患者提供 鼠源性脑转移3D类器官研究项目1中的辐射反应，探索复杂的 在项目1和2中，转移上皮和免疫微环境之间的串扰， 在项目3中用于模拟T细胞引发的新型淋巴样器官。Bassik实验室将提供创新 CRISPR工具用于项目1中的靶向遗传筛查，以探索肿瘤相关基因与肿瘤相关蛋白之间的相互作用。 小胶质细胞和转移性上皮细胞，沿着工程iPSC为项目3开发疫苗策略 治疗脑转移Pitteri实验室将为项目1-3提供蛋白质组学分析， 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 对转移性疾病的见解。这些资源将共同为SBMC的各种调查提供支持 改进治疗方法。