Cancer Epigenetics Research Program

癌症表观遗传学研究计划

基本信息

批准号：
10443641
负责人：
RAMIN SHIEKHATTAR
金额：
$ 3.96万
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/10443641
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 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位调查人员组成。由Ramin Shiekhattar博士共同领导该计划旨在将基本和临床研究纳入癌症领域表观遗传学以查明有助于癌症风险，主动性，进展和治疗的表观遗传因素考虑到Sylvester集水区内的特定需求，回应。实现这些目标，CE计划包括三个特定目的：1）阐明致癌分子与癌症突变的表观遗传调节剂相关的机制； 2）定义增强器和转录重编程是通过癌症中异常信号转导级联反应而进行的； 3）验证临床前和临床中热干预和生物标志物发展的表观遗传靶标研究。目前，计划成员获得550万美元的年度直接同行评审资金，其中包括220万美元来自NCI和150万美元的其他NIH机构。 CE的研究工作在很大程度上依赖于Sylvester的共享资源尤其是Onco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计划促进了强大的内部和编程间合作以及间机构合作以利用基本，转化和成员专业知识的深度和广度临床研究和开发创新的方法来改善癌症对西尔维斯特的影响集水区，一个四县地区，称为南佛罗里达州。例如，CE与肿瘤生物学研究计划，以了解致癌信号通路与癌症的表观遗传学放松管制，以及癌症控制研究计划，以了解特定环境和社会经济差异会影响表观基因组并影响癌症倡议，并进展。这些协作的努力得到了快速扩展的同行评审投资组合的支持资金，包括NCI先驱奖，Multi-Pi R01补助金，最近被授予白血病和淋巴瘤协会（LLS）学者奖和LLS专业研究计划项目项目赠款。一些研究人员发起的研究也来自CE计划的发现。此外，CE成员有自2014年以来发表了143份与癌症相关的论文； 24％代表前编程，29％表示程序化，77％反映了多机构的合作。 CE的一些主要贡献包括1）解剖DNA甲基化和羟甲基在血液系统恶性肿瘤中的作用； 2）目标 Hisstone的读者，作家和AML的橡皮擦； 3）定义BAP1和ASXL1在卵巢黑色素瘤中的作用它们对组蛋白甲基化和泛素化的贡献； 4）发现增强剂RNA（ERNAS）并靶向癌症中的ERNAS影响致病基因表达和细胞生长。