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 Sylvester综合癌症中心（Sylvester）肿瘤生物学（TB）研究计划建立了 2014年，组成42位代表11个部门/学科的调查员，具有专业知识致癌信号传导，应力反应，发育途径，免疫信号传导和炎症。领导 TB计划拥有当前的研究资金投资组合为1,160万美元直接同行评审的资金，其中包括来自国家癌症研究所（NCI）的590万美元。该计划的收藏夹并协作将癌症研究工作整合到该计划和中心 - 宽，催化高影响力的发现，以满足西尔维斯特四县的未满足需求集水区。该计划的主要目标是了解癌症的出现和进步并定义癌细胞，肿瘤基质和免疫细胞之间的主要相互作用。结核病成员也使用该知识确定针对基本生物学和分子特征的新型治疗方法癌细胞。为了实现这些目标，结核病成员优先考虑三个科学目标：1）阐明肿瘤倡议和进展的机制； 2）确定注射和免疫学如何影响肿瘤发生和肿瘤微环境； 3）研究生物学和分子基础有针对性的治疗方法。 Sylvester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，ONCO基因组学，流式细胞术以及行为和基于社区的行为研究 - 支持结核病研究工作。自2014年以来，计划成员已发布了337个同行评审，与癌症相关的论文：33％代表合作团队科学，21％是概括性的（高于14％在2014年），有18％的程序间截图（比2014年的13％增加），有66％涉及与外部合作机构和28％的机构包括来自NCI指定的癌症中心的科学家。最近的结核病研究突出显示包括氧化应激和抗氧化剂反应促进对雄激素的抗性的发现在cast割前列腺癌中的剥夺治疗；可以使用针对Apatmer的siRNA方法靶向T细胞并增强抗肿瘤免疫组织化学；依赖于刺激的胞质DNA感应培养媒体先天免疫识别免疫原性肿瘤； NACK是Notch转录激活的组成部分可以针对癌细胞的复合物； CK1α（SSTC3）的小分子活化剂，充当新型 Wnt抑制剂具有最小的GI毒性； Jak/Stat3和HSP70重塑肿瘤微环境和胰腺癌中介导治疗性。大写Sylvester的基础设施，结核病共同领导者与计划成员合作，促进科学发现并制定新计划利用新兴的科学思想和技术来促进合作，创新，集水区与与之相关的协作基础研究。