Cancer Epigenetics Research Program

癌症表观遗传学研究计划

• 批准号: 10670848
• 负责人: RAMIN SHIEKHATTAR
• 金额: $ 4.08万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 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/10670848
• 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; DNMT3a; Dedications; 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; Institution; Maintenance; Malignant Neoplasms; Mentors; Modification; Molecular; Mutate; Mutation; Myeloproliferative disease; Normal Cell; Nucleic Acid Regulatory Sequences; Oncogenic; Paper; 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; bench to bedside; biomarker development; 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; outcome disparities; posttranscriptional; precision medicine; preclinical study; programs; promoter; recruit; response; restraint; socioeconomic disparity; targeted treatment; therapy development; transcriptional reprogramming; treatment response; tumor progression; tumorigenesis; virulence gene

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.

项目概要：癌症表观遗传学研究 西尔维斯特综合癌症中心（西尔维斯特）癌症表观遗传学（CE）研究计划， 该小组于2014年成立，由来自7个部门的18名调查员组成。由拉明谢克哈塔博士共同领导， 和玛丽亚菲格罗亚，医学博士，该计划旨在纳入基础和临床研究领域的癌症 表观遗传学，以查明表观遗传因素，有助于癌症的风险，开始，进展和治疗 考虑到西尔维斯特集水区内存在的具体需求，做出响应。实现 这些目标，CE计划包括三个具体目标：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， 通过癌症中的异常信号转导级联施加的转录重编程;和3） 临床前和临床中用于治疗干预和生物标志物开发的表观遗传靶点 问题研究目前，项目成员每年获得550万美元的直接同行评审资金，其中包括220万美元。 NCI和其他NIH研究所提供的150万美元。CE的研究工作在很大程度上依赖于西尔维斯特的共享 资源，特别是肿瘤基因组学，流式细胞术，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跨计划的合作，以及跨 机构合作，以利用成员在基础、翻译和 临床研究和开发创新的方法，以改善癌症的影响，在西尔维斯特的 集水区，一个四县的地区被称为南佛罗里达。例如，CE与 肿瘤生物学研究计划，以了解致癌信号通路之间的相互作用， 癌症的表观遗传失调，并与癌症控制研究计划，以了解如何具体 环境和社会经济差异影响表观基因组并影响癌症的发生， 进展这些合作努力得到了迅速扩大的同行评审组合的支持。 资金，包括NCI先锋奖，多PI R 01赠款，最近授予白血病和淋巴瘤 社会（LLS）学者奖，和LLS研究计划项目赠款的专业中心。几 CE项目发现中也出现了由制药商发起的研究。此外，行政长官成员还 自2014年以来发表了143篇癌症相关论文; 24%代表项目内，29%代表跨项目， 77%是计划性的，77%是多机构合作。行政长官的主要贡献包括： 分析DNA甲基化和羟甲基化在血液系统恶性肿瘤中的作用; 2）靶向 AML中的组蛋白读取器、写入器和擦除器;以及3）确定BAP 1和ASXL 1在葡萄膜黑色素瘤中的作用 以及它们对组蛋白甲基化和泛素化的贡献; 4）增强子RNA（eRNA）的发现 以及靶向癌症中的eRNA以影响致病基因表达和细胞生长。