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.

项目概要 作为 E. Alejandro Sweet-Cordero 实验室的成员，我的努力旨在执行 资助、手稿和实验室总体目标的计算方面以及指导其他人 实验室成员。我们项目的目标是研究癌症进展的机制并获得临床结果 儿科和成人实体瘤的相关见解。 R50 NCI 研究专家奖将提供 我拥有必要的资金来继续进一步开发我的计算工具并持续支持 以下 NCI 资助的项目： (1) 儿科实体瘤先进临床前模型的开发 （R01CA243555）。该项目有三个主要目标：a) 验证患者组织和患者是否匹配 衍生异种移植物 (PDX) 或 PDX 衍生细胞系在转录和分子上相似； b）利用高 通量分析以指定用于测试的药物靶标，以及 c) 使用单细胞研究耐药性 RNAseq 技术。 (2) 肺癌新型蛋白质治疗药物的开发 （R01CA225103）。这笔赠款的主要目标是了解 CLCF1-CNTFR 的生物学，因为它与 成人肺癌并评估工程化“诱饵”CNTFR 受体的协同结果 (eCNTFR) 与其他化合物（例如 eCNTFR+ PDL1 检查点抑制剂）。 (3)考察长的作用 肉瘤发病机制中的非编码 RNA (lncRNA) (R01CA211657)。这笔赠款的目标是 阐明 lncRNA EWSAT1/2 在 EWS-FLI 抑制的增强子位点染色质重塑中的作用， 利用 ChIRP-Seq 和 ATACseq。从之前的 lncRNA CRISPR 介导中发现的其他 lncRNA 还将利用体外和体内研究干扰筛选在尤文肉瘤中的作用 模型。我不断努力开发软件和计算管道不仅会实现目标 这些 NCI 拨款不仅符合我的长期职业目标，而且有利于更广泛的癌症研究 社区。