Tumor Biology Research Program

肿瘤生物学研究计划

基本信息

批准号：
10190864
负责人：
WAEL EL-RIFAI
金额：
$ 3.89万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-10 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10190864
关键词：
Acquired Immunodeficiency Syndrome Address Antioxidants Area Argentina Award Basic Science Behavioral Research Bioinformatics Biological Biology Biostatistics Shared Resource Cancer Burden Cancer Center Cancer Center Support Grant Catchment Area Cells Cellular Stress Clinical Collaborations Complex Comprehensive Cancer Center County Cues DNA Development Discipline Doctor of Philosophy Environment Event Faculty Flow Cytometry Fostering Funding Funding Mechanisms Gastrointestinal Diseases Goals HIV Heat-Shock Proteins 70 Immune Immune signaling Immunity Inflammation Inflammatory Infrastructure Institution Interdisciplinary Study International Intervention Investments Knowledge Leadership Ligands Localized Malignant Neoplasm Malignant Neoplasms Malignant neoplasm of pancreas Mediating Mentors Mission Molecular National Cancer Institute Non-Malignant Oncogenic Operative Surgical Procedures Oxidation-Reduction Oxidative Stress Paper Pathway interactions Peer Review Productivity Proteins Publications Publishing Research Research Personnel Research Support Research Training Resistance STAT3 gene Science Scientist Signal Pathway Signal Transduction Small Interfering RNA Strategic Planning Stress Stromal Cells Structure Surgical Oncology T-Lymphocyte Technology Therapeutic Therapeutic Intervention Tissues Toxic effect Training Transcriptional Activation Tumor Biology Tumor Immunity United States National Institutes of Health Universities Work androgen deprivation therapy anticancer research aptamer base biological adaptation to stress cancer cell cancer genomics career career development castration resistant prostate cancer cohesion collaborative environment community based research experience fitness hormonal signals immune function immunogenic inhibitor/antagonist innovation knowledge base meetings member neoplastic cell next generation novel novel therapeutic intervention programs recruit resistance mechanism response targeted treatment therapy resistant tumor tumor growth tumor immunology tumor initiation tumor microenvironment tumor progression tumorigenesis

项目摘要

PROJECT SUMMARY: TUMOR BIOLOGY RESEARCH PROGRAM The Sylvester Comprehensive Cancer Center (Sylvester) Tumor Biology (TB) Research Program, established in 2014, comprises 42 investigators representing 11 departments/disciplines with expertise spanning oncogenic signaling, stress response, developmental pathways, immune signaling, and inflammation. Led by Co-Leaders Wael El-Rifai, MD, PhD, and Ashok Saluja, PhD, the TB program holds a current research funding portfolio of $11.6M in direct peer-reviewed funding, including $5.9M from the National Cancer Institute (NCI). The program facilitates and collaboratively integrates cancer research efforts within the program and center- wide, while catalyzing high-impact discoveries to address the unmet needs of Sylvester’s four-county catchment area. The program’s primary goals are to understand how cancers arise and progress and to define key interactions between cancer cells, tumor stroma, and immune cells. TB members also use that knowledge to identify novel therapeutic approaches that target the fundamental biological and molecular features of cancer cells. To accomplish these goals, TB members have prioritized three scientific aims: 1) Elucidate mechanisms underlying tumor initiation and progression; 2) Determine how inflammation and immunity influence tumorigenesis and the tumor microenvironment; and 3) Investigate the biological and molecular basis of targeted therapeutic approaches. Expertise and technical support from Sylvester’s four shared resources— Biostatistics and Bioinformatics, Onco-Genomics, Flow Cytometry, and Behavioral and Community-Based Research—support TB research efforts. Since 2014, program members have published 337 peer-reviewed, cancer-relevant papers: 33% represent collaborative team science, 21% are intra-programmatic (up from 14% in 2014), 18% are inter-programmatic (up from 13% in 2014), 66% involve collaboration with external institutions, and 28% include scientist from NCI-designated cancer centers. Recent TB research highlights include the discoveries that oxidative stress and antioxidant response promote resistance to androgen deprivation therapy in castration-resistant prostate cancers; aptamer-targeted siRNA approaches can be used to target T cells and enhance anti-tumor immunity; STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors; NACK is an integral component of NOTCH transcription activation complex that can be targeted in cancer cells; a small molecular activator of CK1α (SSTC3) that acts as a novel WNT inhibitor with minimal GI toxicity; and JAK/STAT3 and HSP70 remodel tumor microenvironment and mediate therapeutic resistance in pancreatic cancer. Capitalizing on Sylvester’s infrastructure, the TB Co- Leaders work with program members to promote scientific discoveries and develop new initiatives that leverage emerging scientific ideas and technologies to foster collaborative, innovative, catchment area-relevant basic research.

项目摘要：肿瘤生物学研究计划西尔维斯特综合癌症中心（Sylvester）肿瘤生物学（TB）研究项目成立 2014 年，由 42 名调查员组成，代表 11 个部门/学科，专业知识涵盖致癌信号、应激反应、发育途径、免疫信号和炎症。结核病项目联合领导者 Wael El-Rifai 博士和 Ashok Saluja 博士拥有当前的研究经费 1160 万美元的直接同行评审资金组合，其中包括来自国家癌症研究所 (NCI) 的 590 万美元。该计划促进并协作整合该计划和中心内的癌症研究工作广泛，同时促进高影响力的发现，以满足西尔维斯特四个县未满足的需求该计划的主要目标是了解癌症如何发生和进展并定义癌症。癌细胞、肿瘤基质和免疫细胞之间的关键相互作用也利用了这些知识。确定针对基本生物学和分子特征的新治疗方法为了实现这些目标，TB 成员优先考虑了三个科学目标：1) 阐明。肿瘤发生和进展的机制 2) 确定炎症和免疫的机制；影响肿瘤发生和肿瘤微环境；3) 研究生物学和分子基础来自西尔维斯特的四个共享资源的专业知识和技术支持 - 生物统计学和生物信息学、肿瘤基因组学、流式细胞术以及行为和社区基础研究——支持结核病研究工作自 2014 年以来，计划成员已发表 337 篇经过同行评审的、癌症相关论文：33% 代表协作团队科学，21% 属于程序内论文（高于 14%） 2014 年），18% 是跨计划的（高于 2014 年的 13%），66% 涉及与外部合作机构，28% 包括来自 NCI 指定癌症中心的科学家。包括氧化应激和抗氧化反应促进雄激素抵抗的发现可以使用针对去势抵抗性前列腺癌的剥夺疗法；靶向 T 细胞并增强抗肿瘤免疫；STING 依赖性胞质 DNA 传感介导先天性；免疫原性肿瘤的免疫识别；NACK 是 NOTCH 转录激活的一个组成部分；可靶向癌细胞的复合物；一种新型的 CK1α (SSTC3) 小分子激活剂 WNT 抑制剂具有最小的胃肠道毒性；JAK/STAT3 和 HSP70 重塑肿瘤微环境并利用西尔维斯特的基础设施，TB Co-介导胰腺癌的治疗耐药性。领导者与计划成员合作，促进科学发现并制定新举措，利用新兴的科学思想和技术来促进与流域相关的协作、创新基础研究。