Utilizing Multi-omics to Facilitate Cancer Biology Research

项目摘要 作为E.Alejandro Sweet-Cordero实验室的一员，我致力于执行 计算方面的拨款，手稿，实验室的总体目标，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 对儿童和成人实体肿瘤的相关见解。R50 NCI研究专家奖将提供 我有必要的资金来继续开发我的计算工具和持续的支持 NCI资助的以下项目：(1)儿童实体肿瘤高级临床前模型的开发 (R01CA243555)。该项目有三个主要目标：a)验证匹配的患者组织和患者- 衍生异种移植(PDX)或PDX衍生的细胞系在转录和分子上相似；b)利用高密度的 吞吐量分析，以提名用于测试的药物靶点，以及c)使用单细胞研究耐药性 RNAseq技术。(2)以蛋白质为基础的肺癌治疗新药物的发展 (R01CA225103)。这项资助的主要目标是了解CLCF1-CNTFR的生物学，因为它与 并评价工程“诱饵”CNTFR受体的协同效应 (ECNTFR)与其他化合物(如eCNTFR PDL1检查点抑制剂)一起使用。(3)调查龙的作用 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抑制的增强子部位染色质重塑中的作用， 利用Chirp-Seq和ATACseq。从先前的由CRISPR介导的lncRNA中发现的其他lncRNA 干扰筛选也将在体外和体内研究它们在尤文肉瘤中的作用 模特们。我正在进行的开发软件和计算管道的努力不仅仅是为了实现这些目标 也符合我的长期职业目标，并使更广泛的癌症研究受益 社区。

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.