TOOLKIT Core

工具包核心

基本信息

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
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/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

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，突出了明显的缺乏我们对肿瘤传播过程的理解。由于缺乏，研究严重阻碍了与生理相关的肿瘤模型和分子工具，用于发现挽救生命的疗法。这斯坦福脑转移财团（SBMC）着重于识别遗传基础调节脑转移，一种治疗选择有限和生存率微薄的疾病。为了支持这个目标， Toolkit Core提供了主机建模领先专家的创新实验解决方案（Calvin博士 KUO），基因组功能屏幕（Michael Bassik博士）和糖蛋白质组学（Sharon Pitteri博士）执行 SBMC中提出的项目。工具包核心团队拥有多样化但完整的专业领域，并且有资格专门解决通过提供新型实验器官，在此RFA：转移研究网络中概述了未满足的需求模型以及尖端的CRISPR和蛋白质组学工具，用于表征和操纵差的了解信号淋巴结驱动脑转移性疾病。具体而言，KUO实验室将提供患者和鼠衍生的脑转移3D器官研究项目1中的辐射反应，探索了复杂的项目1和2中的转移性上皮和免疫小组微环境之间的串扰，并发展用于建模项目3中T细胞启动的新型淋巴类器官。BassikLab将提供创新的项目1中针对目标遗传筛查的CRISPR工具，以探索与肿瘤相关的相互作用小胶质细胞和转移性上皮细胞，以及针对项目3的工程IPSC，以开发疫苗策略用于脑转移。 Pitteri实验室将为1-3的项目提供蛋白质组学分析，以表征糖基化模式和脑转移组织和器官的特征，从而提供关键的生物学对转移性疾病的见解。这些资源将共同赋予潜水员对SBMC的调查采取改进的治疗方法。