Mechanisms in Cancer Evolution Program

癌症进化机制计划

基本信息

批准号：
10239129
负责人：
Susan M Rosenberg
金额：
$ 4.01万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10239129
关键词：
AIDS related cancer Address Aging Bacteria Basic Science Biochemistry Bioinformatics Biological Biological Markers Biology Cancer Center Cancer Center Support Grant Cancer Model Catchment Area Cell Cycle Regulation Cell model Cells Chromosomes Collaborations Communicable Diseases Communities DNA Damage DNA Repair DNA biosynthesis Data Detection Diagnostic Direct Costs Epigenetic Process Evolution Flow Cytometry Funding Gene Expression Genetic Genetic Heterogeneity Genetic Recombination Genome Genomic Imprinting Genomics Goals Heritability Heterogeneity Human Human Genetics Human Genome Immunology Individual Interest Group Intervention Journals Maintenance Malignant Neoplasms Malignant neoplasm of cervix uteri Malignant neoplasm of liver Manuscripts Mediating Medicine Metabolic Metagenomics Methods Microbe Microbiology Mission Modeling Molecular Molecular Biology Molecular Genetics Molecular Virology Mus Mutagenesis Mutation Nutritional Obesity associated disease Organoids Paper Pathology Patients Pediatric Oncology Peer Review Phenotype Prevention Research Proteins Proteome Proteomics Publishing RNA Research Research Personnel Research Support Research Training Resistance Resource Sharing Rice Risk Screening for cancer Structure Texas Therapeutic United States National Institutes of Health Universities Variant Viral Virus Work Yeasts austin biomarker identification cancer genome cancer prevention cell killing college conventional therapy diagnostic biomarker epigenomics host microbiome human data imaging informatics inflammatory disease of the intestine inter-institutional meetings member metabolomics microbiome microscopic imaging mouse model new technology non-genetic novel nutrition potential biomarker programs promoter recruit single molecule telomere therapeutic target tool transcriptome transcriptomics tumorigenesis virome

项目摘要

Mechanisms in Cancer Evolution Program (MCEP) PROJECT SUMMARY The mission of the Mechanisms in Cancer Evolution Program (MCEP) at the DLDCCC is focused on understanding molecular mechanisms that generate heterogeneity (genetic and non-genetic or epi-genetic) and environmental drivers that spur evolution of cancers. Evolution occurs by variation, which creates heterogeneity and selection. Heterogeneity is generated by intrinsic genomic and non-genetic phenotype-plasticity mechanisms, as well as by alteration of cellular programs by extrinsic viruses, the microbiome, and nutritional modulation. The goal of the MCEP is fundamental basic science discovery of how these molecular mechanisms work. New paradigms discovered can open new translational directions (throughout the DLDCCC Programs and by others), including novel evolutionary biomarkers, diagnostic, preventative, and therapeutic tools. For example, whereas conventional therapies kill cells or stop them from growing (are anti-proliferative), proposed novel interventions that would slow evolution, promise new and fundamentally different ways to inhibit oncogenesis and thwart resistance. Also, identification of biomarkers of highly evolvable cells may allow detection of at-risk individuals, and earlier detection of cancers. The MCEP currently has 26 members: 25 are Research members from the BCM Departments of Molecular and Human Genetics, Molecular Virology and Microbiology, Biochemistry and Molecular Biology, Pediatrics-Oncology, Medicine-Infectious Disease, Pathology and Immunology, and the Huffington Center on Aging; one is an adjunct member, appointed at the University of Texas, Austin. Members of the MCEP published a total of 576 cancer-related papers in the previous funding period with 25% in journals with Impact Factors of 10 or above. Of the 576 manuscripts, 11% represented intra- programmatic, 46% inter-programmatic, and 68% inter-institutional collaborations. The MCEP currently has a total of $10.5 million in selected cancer-relevant funding (direct costs per annum), which includes $2 million from NCI, $5.8 million in other NIH funding and $2.2 million in other peer reviewed funding mostly from the Cancer Prevention and Research Initiative of Texas (CPRIT). The two MCEP Aims encompass mechanisms of promotion of heterogeneity by: (1) Intrinsic Evolution Promoters (mutation, genome rearrangement, recombination, epigenetic heritable protein- and RNA-error-mediated variation); and (2) Extrinsic Evolution Promoters, including viruses, microbes generally, the microbiome, and nutritional modulators of both host and microbiome. The CCSG supports this Research Program by providing key Shared Resources, particularly High- Parameter Flow Cytometry; Advanced Microscopy and Image Informatics; Genomic, Transcriptomic, Epigenomic and Single-Cell, Metabolomics, and Proteomics; as well as administrative support for meetings, clubs and interest groups, and pilot funding and recruitment funds.

癌症进化计划（MCEP）的机制项目摘要 DLDCCC的癌症进化计划（MCEP）中的机制的任务集中在了解产生异质性（遗传和非遗传或表皮遗传学）的分子机制，并且刺激癌症进化的环境驱动因素。进化是通过变异发生的，这会产生异质性和选择。异质性是由固有基因组和非遗传表型塑性产生的机制以及通过外部病毒，微生物组和营养的细胞程序改变了细胞程序调制。 MCEP的目标是基础科学发现这些分子机制如何工作。发现的新范式可以打开新的翻译方向（在整个DLDCCC程序中，其他），包括新颖的进化生物标志物，诊断，预防和治疗工具。例如，而常规疗法杀死细胞或阻止它们生长（具有抗增殖），但提出了新颖会减慢进化的干预措施，承诺新的和根本不同的方式来抑制肿瘤发生和阻止抵抗。同样，鉴定高度可变细胞的生物标志物可能允许检测到处于危险中个人，以及早期发现癌症。 MCEP目前有26名成员：25位研究成员来自分子和人类遗传学的BCM部门，分子病毒学和微生物学，生物化学和分子生物学，儿科肿瘤学，医学疾病，病理学和病理学免疫学和赫芬顿衰老中心；一个是在大学任命的兼职成员德克萨斯州，奥斯汀。 MCEP的成员在先前的资金中总共发表了576篇与癌症有关的论文期刊为25％，影响因素为10或更高。在576个手稿中，有11％代表内部程序化，46％的程序间和68％的机构间合作。 MCEP当前有一个总计1050万美元的一选癌症与癌症的资金（每年直接费用），其中包括200万美元 NCI，其他NIH资金为580万美元，其他同行的220万美元审查了主要来自癌症的资金德克萨斯州的预防与研究计划（CPRIT）。这两个MCEP的目的包括促进异质性通过：（1）固有进化启动子（突变，基因组重排，重组，表观遗传性可遗传的蛋白质和RNA - 异常介导的变异）；（2）外部进化启动子，包括病毒，微生物，通常的宿主和营养调节剂微生物组。 CCSG通过提供关键的共享资源，尤其是高级资源来支持该研究计划参数流式细胞仪；高级显微镜和图像信息学；基因组，转录组，表观基因组和单细胞，代谢组学和蛋白质组学；以及对会议的行政支持，俱乐部和利益集团，以及试点资金和招聘资金。