Cancer Epigenetics Research Program

癌症表观遗传学研究计划

基本信息

批准号：
10190863
负责人：
RAMIN SHIEKHATTAR
金额：
$ 3.85万
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/10190863
关键词：
Acute Myelocytic Leukemia Affect Area Award Basic Science Binding Binding Sites Biochemical Bioinformatics Bioinformatics Shared Resource Biological Assay Biometry Cancer Biology Cancer Center Support Grant Cancer Control Research Program Cancer Model Catchment Area Cells Chromatin Clinical Research Collaborations Communities Comprehensive Cancer Center County Cytosine Cytotoxic agent DNA DNA Methylation DNA Sequence Development Diagnosis Differentiation Inducer Diffuse Distal Doctor of Philosophy Enhancers Epigenetic Process Faculty Florida Flow Cytometry Fostering Funding Future Gene Expression Gene Expression Regulation Genes Genetic Enhancer Element Genetic Transcription Genomics Glioma Grant Growth Growth Factor H3 K27M mutation Hematologic Neoplasms Heritability Histone Deacetylase Inhibitor Histones Human Immunotherapy Infrastructure Institutes Maintenance Malignant Neoplasms Mentors Modification Molecular Mutate Mutation Myeloproliferative disease Normal Cell Nucleic Acid Regulatory Sequences Oncogenic Paper Pathogenicity Patient-Focused Outcomes Patients Peer Review Phenotype Postdoctoral Fellow Prognosis Program Research Project Grants Publishing RNA Reader Regulation Research Research Personnel Resource Sharing Resources Role Signal Pathway Signal Transduction Site Societies Solid Neoplasm Specialized Center Specimen Therapeutic Training Training and Education Translational Research Tumor Biology Ubiquitination United States National Institutes of Health Uveal Melanoma Validation Work anticancer research base bench to bedside biomarker development biomarker identification cancer cell cancer genomics cancer initiation cancer risk cancer therapy cell growth epigenetic marker epigenetic regulation epigenome genome-wide analysis graduate student histone methylation histone modification improved inhibitor/antagonist innovation insight inter-institutional leukemia/lymphoma member mouse model mutant novel precision medicine preclinical study programs promoter recruit response socioeconomic disparity targeted treatment therapy development transcriptional reprogramming treatment response tumor progression tumorigenesis

项目摘要

PROJECT SUMMARY: CANCER EPIGENETICS RESEARCH PROGRAM The Sylvester Comprehensive Cancer Center (Sylvester) Cancer Epigenetics (CE) Research Program, established in 2014, comprises 18 investigators from seven departments. Co-led by Ramin Shiekhattar, PhD, and Maria Figueroa, MD, the program aims to incorporate basic and clinical research in the field of cancer epigenetics to pinpoint epigenetic factors that contribute to cancer risk, initiation, progression, and treatment response, taking into consideration the specific needs present within Sylvester’s catchment area. To achieve these objectives, the CE program encompasses three specific aims: 1) Elucidate the oncogenic molecular mechanisms associated with epigenetic regulators that are mutated in cancer; 2) Define the enhancer and transcriptional reprogramming that is imposed through aberrant signal transduction cascades in cancer; and 3) Validate epigenetic targets for therapeutic intervention and biomarker development in pre-clinical and clinical studies. Currently, program members receive $5.5M in annual direct peer-reviewed funding, including $2.2M from the NCI and $1.5M from other NIH Institutes. CE’s research efforts rely heavily on Sylvester’s shared resources, notably the Onco-Genomics, Flow Cytometry, and Biostatistics and Bioinformatics Shared Resources. The CE program fosters robust intra- and inter-programmatic collaborations as well as inter- institutional collaborations to leverage the depth and breadth of member expertise in basic, translational, and clinical research and develop innovative approaches to ameliorate the impact of cancer in Sylvester’s catchment area, a four-county area known as South Florida. For instance, CE works collaboratively with the Tumor Biology Research Program to understand the interplay between oncogenic signaling pathways and epigenetic deregulation in cancer, and with the Cancer Control Research Program to understand how specific environmental and socio-economic disparities impact the epigenome and influence cancer initiation and progression. These collaborative efforts are supported by a rapidly expanding portfolio of peer-reviewed funding, including an NCI Pioneer Award, multi-PI R01 grants, a recently awarded Leukemia and Lymphoma Society (LLS) Scholar Award, and an LLS Specialized Center of Research program project grant. Several investigator-initiated studies are also emerging from CE program discoveries. Furthermore, CE members have published 143 cancer-relevant papers since 2014; 24% represent intra-programmatic, 29% represent inter- programmatic, and 77% reflect multi-institutional collaborations. Some of CE’s major contributions include 1) dissecting the role of DNA methylation and hydroxymethylation in the hematological malignancies; 2) targeting histone readers, writers, and erasers in AML; and 3) defining the role of BAP1 and ASXL1 in uveal melanoma and their contribution to histone methylation and ubiquitination; and 4) discovering of enhancer RNAs (eRNAs) and targeting eRNAs in cancer to affect pathogenic gene expression and cellular growth.

项目摘要：癌症表观遗传学研究计划西尔维斯特综合癌症中心 (Sylvester) 癌症表观遗传学 (CE) 研究计划，成立于 2014 年，由来自七个部门的 18 名研究人员组成，由 Ramin Shiekattar 博士共同领导。和玛丽亚·菲格罗亚医学博士，该项目旨在将癌症领域的基础和临床研究结合起来表观遗传学可查明导致癌症风险、发生、进展和治疗的表观遗传因素响应，考虑到西尔维斯特流域内存在的具体需求。这些目标中，CE 计划包含三个具体目标：1) 阐明致癌分子与癌症中突变的表观遗传调节因子相关的机制；2) 定义增强子和通过癌症中异常信号转导级联施加的转录重编程；以及3) 验证临床前和临床治疗干预和生物标志物开发的表观遗传学目标目前，项目成员每年获得 550 万美元的直接同行评审资金，其中 220 万美元 CE 的研究工作在很大程度上依赖于 Sylvester 的共享。资源，特别是肿瘤基因组学、流式细胞术以及生物统计学和生物信息学共享资源。CE 计划促进了项目内和项目间的合作以及项目间的合作。机构合作，以利用成员在基础、转化和领域专业知识的深度和广度临床研究并开发创新方法来减轻癌症对西尔维斯特氏症的影响例如，CE 与南佛罗里达州的一个四县地区合作。肿瘤生物学研究计划旨在了解致癌信号通路与癌症中的表观遗传放松管制，并与癌症控制研究计划一起了解具体如何环境和社会经济差异影响表观基因组并影响癌症的发生和发展这些协作努力得到了快速扩展的同行评审组合的支持资助，包括 NCI 先锋奖、多项 PI R01 资助、最近授予的白血病和淋巴瘤学会 (LLS) 学者奖和 LLS 专业研究中心计划项目资助。研究者发起的研究也源于 CE 计划的发现。此外，CE 成员还发现了这一点。自 2014 年以来发表了 143 篇癌症相关论文；24% 为项目内论文，29% 为项目间论文计划性的，77% 反映了多机构合作，CE 的一些主要贡献包括 1) 剖析 DNA 甲基化和羟甲基化在血液恶性肿瘤中的作用 2) 靶向； AML 中的组蛋白读取器、写入器和擦除器；3) 定义 BAP1 和 ASXL1 在葡萄膜黑色素瘤中的作用及其对组蛋白甲基化和泛素化的贡献；4) 增强子 RNA (eRNA) 的发现并针对癌症中的 eRNA 来影响致病基因表达和细胞生长。