Mechanisms of Oncogenesis Research Program

肿瘤发生机制研究计划

基本信息

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
项目类别：
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

项目摘要

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.

癌发生机制计划：摘要肿瘤发生机制 (MOO) 计划的目标是阐明放松管制的遗传和肿瘤发生机制。表观遗传事件驱动肿瘤的发生和进展，并确定癌症相关的治疗靶点。 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 个部门来自5所大学。自2016年以来，共招募了20名教师，其中包括14名早期研究者（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在肿瘤发生中的作用； 3）将 MOO 的发现转化为新的治疗方法接近。与目标 3 一致，Guryanova 发现 DNMT3A 突变 AML 对低剂量阿糖胞苷，导致与 Al-Mansour 合作开发治疗试验 (CTHR)，由基础科学和临床研究 AD 以及 IIT 智库培育。 MOO 有一个同行经审查的直接成本每年超过 900 万美元（自 2019 年以来增加超过 10%），代表 59 个同行评审的资金基础其中 24 个项目来自 NCI（直接成本 380 万美元），包括 NCI P01、NIH 和其他同行评审项目来源。自 2019 年以来，已向新招募的 ESI 授予了 10 项新资助。 MOO 培养内部和外部通过工作组重点会议（表观遗传学、肿瘤病毒学和肺癌症（学区优先事项）、研讨会和年度计划务虚会。这些互动导致 11 项活跃多 PI 同行评审资助和多机构 NCI P01。 MOO合作的成功也自 2016 年以来，762 篇癌症相关出版物证明了这一点，其中 20% 的影响因子 >10。此外，19%的出版物是跨项目的，23% 是项目内的，74% 是跨机构的。莫奥成员还获得了 36 项新专利。 MOO导师培养了162名研究生和71名博士后，其中 45% 为女性，10% 为代表性不足的少数族裔 (URM)。共有 14 名学员（9 名女性；3 名 URM）由 NIH 培训补助金支持。吴担任社区外展项目联络人和参与度（COE）。她和 Renne 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。 Renne 与 COE 合作，共同为 Citizen 开发 UFHCC 癌症课程科学家们。 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：在 AD for Diversity 的协调和指导下，参与实习生和教师的招聘，公平和包容。与战略计划“Momentum 2027”保持一致，未来目标将集中于范式转变的基本发现和治疗靶点的识别，目标是临床转化 CTHR 和 CCPS 成员致力于解决 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 资助，以及 MOO 的发现转化为临床。