Utilizing Multi-omics to Facilitate Cancer Biology Research

利用多组学促进癌症生物学研究

• 批准号: 10733768
• 负责人: Alex Lee
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10733768
• 关键词: ATAC-seq; Adult; Advanced Development; Award; Bioinformatics; Biology; Cancer Biology; Cell Line; Childhood; Childhood Solid Neoplasm; Clustered Regularly Interspaced Short Palindromic Repeats; Communities; Computer software; Data Sources; Development; Drug Targeting; Drug resistance; Engineering; Enhancers; Ewings sarcoma; Funding; Genetic Transcription; Goals; Grant; Immune checkpoint inhibitor; In Vitro; Laboratories; Malignant neoplasm of lung; Manuscripts; Mediating; Mentors; Molecular; Outcome; Pathogenesis; Patients; Pre-Clinical Model; Proteins; Publishing; Repression; Research; Role; Site; Solid Neoplasm; Specialist; Technology; Testing; Therapeutic; Tissues; Untranslated RNA; anticancer research; career; chromatin isolation by RNA purification sequencing; chromatin remodeling; clinically relevant; computational pipelines; computerized tools; high throughput analysis; in vivo Model; insight; member; multiple omics; novel; patient derived xenograft model; programmed cell death ligand 1; receptor; sarcoma; single-cell RNA sequencing; software development; tumor progression

Project Summary As a member of the E. Alejandro Sweet-Cordero laboratory my efforts are directed at executing the computational aspects of the grants, manuscripts, and the general goals of the lab as well as mentoring other lab members. The goals of our projects are to study the mechanism of cancer progression and obtain clinically relevant insights for pediatric and adult solid tumors. The R50 NCI Research Specialist Award would provide me with the necessary funds to continue to further develop my computational tools and ongoing support for the following NCI-funded projects: (1) Development of Advanced Preclinical Models for Pediatric Solid Tumors (R01CA243555). There are three main goals to this project: a) verify that matched patient tissue and patient- derived xenografts (PDX) or PDX-derived cell lines are transcriptionally and molecularly similar; b) utilize high- throughput analyses to nominate drug targets for testing, and c) study drug resistance using single-cell RNAseq technologies. (2) Development of Novel Protein-based Therapeutics for Lung Cancer (R01CA225103). The main goals of this grant are to understand the biology of CLCF1-CNTFR as it relates to adult lung cancer and evaluate the synergistic outcomes of the engineered “decoy” CNTFR receptor (eCNTFR) with other compounds (e.g., eCNTFR+ PDL1 checkpoint inhibitor). (3) Investigate the Role of Long Non-coding RNAs (lncRNA) in Sarcoma Pathogenesis (R01CA211657). The goals of this grant are to elucidate the role of lncRNA EWSAT1/2 in chromatin remodeling at EWS-FLI repressed enhancer sites, utilizing ChIRP-Seq and ATACseq. Other lncRNAs revealed from a prior lncRNA CRISPR-mediated interference screen will also be investigated for their role in Ewing Sarcoma using both in vitro and in vivo models. My ongoing efforts to develop software and computational pipelines will not only go toward the goals of these NCI grants but also align with my long-term career goals and benefit the broader cancer research community.

项目摘要 作为E.亚历杭德罗·斯威特-科尔德罗实验室我的努力是针对执行 计算方面的赠款，手稿，和实验室的一般目标，以及指导其他 实验室成员我们项目的目标是研究癌症进展的机制，并在临床上获得 儿童和成人实体瘤的相关见解。R50 NCI研究专家奖将提供 我与必要的资金，继续进一步发展我的计算工具和持续的支持， 国家癌症研究所资助的项目有：（1）儿童实体瘤的先进临床前模型的开发 （R01CA243555）。该项目有三个主要目标：a）验证匹配的患者组织和患者- 衍生的异种移植物（PDX）或PDX衍生的细胞系在转录和分子上是相似的; B）利用高- 通量分析以指定用于测试的药物靶标，以及c）使用单细胞生物技术研究耐药性。 RNAseq技术。(2)肺癌蛋白质治疗新进展 （R01CA225103）。这项资助的主要目标是了解CLCF 1-CNTFR的生物学，因为它涉及到 成人肺癌，并评估工程“诱饵”CNTFR受体的协同效果 （eCNTFR）与其他化合物（例如，eCNTFR+ PDL 1检查点抑制剂）。(3)研究Long的作用 肉瘤发病机制中的非编码RNA（lncRNA）（R 01 CA 211657）。该补助金的目标是 阐明lncRNA EWSAT 1/2在EWS-FLI抑制增强子位点的染色质重塑中的作用， 利用ChIRP-Seq和ATACseq。其他lncRNA从先前的lncRNA CRISPR介导的 干扰筛选也将在体外和体内研究它们在尤文肉瘤中作用 模型我正在努力开发软件和计算管道， 这些NCI赠款，但也符合我的长期职业目标，并有利于更广泛的癌症研究 社区