Mechanisms of Oncogenesis Research Program

肿瘤发生机制研究计划

• 批准号: 10625757
• 负责人: Lizi Wu
• 金额: $ 7.78万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625757
• 关键词: Abbreviations; Address; Affect; Apoptotic; Area; Award; BCL2L1 gene; Basic Science; Biology; Biomedical Research; Biometry; Cancer Biology; Cancer Burden; Cancer Center; Cancer Center Support Grant; Cancer Control; Catchment Area; Chromatin; Clinic; Clinical; Clinical Research; Collaborations; Colorectal Cancer; Communities; Community Outreach; Confocal Microscopy; Cytarabine; DNA Tumor Viruses; DNMT3a; Development; Direct Costs; Disease; Dose; Educational Curriculum; Enzymes; Epigenetic Process; Event; Faculty; Florida; Flow Cytometry; Focus Groups; Fostering; Funding; Future; Genetic; Goals; Grant; Head Cancer; Health; Hematologic Neoplasms; Human; Human Herpesvirus 4; Human Herpesvirus 8; Immune response; Immunity; In Vitro; Infrastructure; Institution; Joints; Last Name; Leadership; Learning; Legal patent; Malignant Neoplasms; Malignant neoplasm of lung; Mentors; Messenger RNA; Methodology; Methods; MicroRNAs; Mission; Modeling; Molecular Target; Monitor; Mus; Mutation; Neck Cancer; Neoplastic Cell Transformation; Oncogenes; Pathway interactions; Peer Review; Peer Review Grants; Phenotype; Population Sciences; Postdoctoral Fellow; Predisposition; Productivity; Proteins; Publications; RNA; Research; Research Personnel; Resource Sharing; Role; STK11 gene; Science; Signal Transduction; Site; Solid; Source; Strategic Planning; Training; Translating; Translations; Tumor Suppressor Genes; Underrepresented Minority; United States National Institutes of Health; Universities; Untranslated RNA; Viral; Woman; Work; base; biomarker development; citizen science; clinical candidate; clinical development; clinical translation; college; community engagement; equity, diversity, and inclusion; graduate student; human DNA; in vivo Model; innovation; investigator-initiated trial; malignant breast neoplasm; meetings; melanoma; member; microbiota; multidisciplinary; mutant; next generation sequencing; novel; novel therapeutic intervention; oncohistone; precision medicine; programs; recruit; success; therapeutic RNA; therapeutic development; therapeutic target; tobacco prevention; treatment response; treatment trial; tumor; tumor initiation; tumor progression; tumorigenesis; virology; working group

MECHANISMS OF ONCOGENESIS PROGRAM: ABSTRACT The objectives of the Mechanisms of Oncogenesis (MOO) program are to elucidate the deregulated genetic and epigenetic events that drive tumor initiation and progression and to identify cancer relevant therapeutic targets. MOO is led by Wu, an expert in cancer signaling and mouse tumor models, and Renne, an expert in tumor virology and non-coding RNAs. MOO is a multidisciplinary group of 38 members, representing 19 departments from 5 colleges. Since 2016, 20 faculty, including 14 early stage investigators (ESIs) were recruited since 2016. The scientific aims of MOO are to: 1) elucidate the role of genetic and epigenetic alterations in cancer; 2) define the role of regulatory RNAs in oncogenesis; and, 3) translate MOO discoveries into novel therapeutic approaches. In alignment with Aim 3, Guryanova discovered that DNMT3A mutant AML was highly sensitive to low dose cytarabine, which has led to the development of a treatment trial in collaboration with Al-Mansour (CTHR), fostered by the ADs for Basic Sciences and Clinical Research and the IIT Think Tank. MOO has a peer- reviewed funding base of >$9M/yr in direct costs (increased >10% since 2019), representing 59 peer-reviewed projects of which 24 are from NCI ($3.8M direct costs), including an NCI P01, NIH, and other peer-reviewed sources. Since 2019, 10 new grants have been awarded to newly recruited ESIs. MOO cultivates intra- and inter- programmatic interactions through working group focused meetings (Epigenetics, Tumor Virology, and Lung Cancer, a catchment area priority), seminars, and annual program retreats. These interactions led to 11 active multi-PI peer-reviewed grants and a multi-institutional NCI P01. The success of MOO collaborations is also demonstrated by 762 cancer-related publications since 2016, 20% with impact factors >10. Moreover, 19% of publications are inter-programmatic, 23% are intra-programmatic, and 74% are multi-institutional. MOO members were also granted 36 new patents. MOO mentors trained 162 graduate students and 71 postdocs, comprised of 45% women and 10% underrepresented minorities (URM). There were 14 trainees (9 women; 3 URM) supported by NIH training grants. Wu serves as the program liaison to community outreach and engagement (COE). She and Renne convey the impact of MOO research to community members and, in return, learn about their needs. Renne, working with COE, co-developed the UFHCC cancer curriculum for Citizen Scientists. MOO leadership and members are committed to increase diversity, equity, and inclusion through participation in recruitment of trainees and faculty, in coordination with and guidance from the AD for Diversity, Equity, and Inclusion. Future goals, in alignment with the strategic plan, Momentum 2027, will be focused on paradigm shifting basic discovery and identification of therapeutic targets with the goal of clinical translation with CTHR and CCPS members to address the cancer burden in the CA. MOO will enhance research in the areas of lung cancer and RNA biology. UFHCC will monitor success based on collaborative publications, new programmatic and MPI grants, and MOO discoveries translated into the clinic.

肿瘤发生机制的研究进展 肿瘤发生机制（MOO）计划的目标是阐明解除调节的遗传和 表观遗传事件，其驱动肿瘤起始和进展，并鉴定癌症相关治疗靶标。 MOO由癌症信号和小鼠肿瘤模型专家Wu和肿瘤专家Renne领导 病毒学和非编码RNA。MOO是一个由38名成员组成的多学科小组，代表19个部门 5个学院。自2016年以来，招募了20名教师，其中包括14名早期研究人员（ESI）。 MOO的科学目标是：1）阐明遗传和表观遗传改变在癌症中的作用; 2）定义 调节RNA在肿瘤发生中作用; 3）将MOO发现转化为新的治疗方法 接近。与Aim 3一致，Guryanova发现DNMT 3A突变AML对以下因素高度敏感： 低剂量阿糖胞苷，这导致了与Al-Mansour合作的治疗试验的发展 （CTHR），由基础科学和临床研究的广告和IIT智库培育。MOO有一个同行- 审查的直接成本资金基础> 900万美元/年（自2019年以来增加>10%），代表59个同行评审 其中24个项目来自NCI（直接费用380万美元），包括NCI P01，NIH和其他同行评审项目 源自2019年以来，已向新招募的ESI颁发了10项新赠款。MOO培养内部和内部- 通过以工作组为重点的会议（表观遗传学、肿瘤病毒学和肺 癌症，集水区优先），研讨会，和年度计划务虚会。这些互动导致了11个活跃的 多PI同行评审赠款和多机构NCI P01。MOO合作的成功也是 自2016年以来的762篇癌症相关出版物证明了这一点，20%的影响因子>10。此外，19%的 出版物是方案间的，23%是方案内的，74%是多机构的。Moo 并获批出三十六项新专利。MOO导师培训了162名研究生和71名博士后， 由45%的妇女和10%的代表性不足的少数民族组成（URM）。共有14名受训人员（9名妇女; 3名 URM）由NIH培训赠款支持。吴担任社区外展的项目联络员， 参与（COE）。她和雷恩向社区成员传达了MOO研究的影响，作为回报， 了解他们的需求。雷恩与COE合作，共同开发了公民UFHCC癌症课程 科学家MOO领导层和成员致力于通过以下方式增加多样性，公平性和包容性 参与学员和教师的招聘，与多样性AD协调和指导， 公平和包容。未来的目标，与战略计划，动力2027年，将集中在 范式转变基本发现和治疗靶点的识别，目标是临床转化， CTHR和CCPS成员解决CA的癌症负担。MOO将加强以下领域的研究 肺癌和RNA生物学。UFHCC将根据合作出版物、新的 计划和MPI赠款，以及MOO发现转化为诊所。