Patient-Matched Stem Cells of the Barrett's-Dysplasia-Adenocarcinoma Sequence

Barretts-不典型增生-腺癌序列的患者匹配干细胞

• 批准号: 9551729
• 负责人: FRANK D. MCKEON
• 金额: $ 18万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-25 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9551729
• 关键词: Accreditation; Adenocarcinoma; Allegra; Animals; Barrett Esophagus; Barrett' s Adenocarcinoma; Behavioral; Behavioral Research; Biochemistry; Biological; Biological Sciences; Biology; Biomedical Research; Cancer Biology; Cancer Center; Caring; Cell Culture Techniques; Cell model; Cells; Cessation of life; Chemicals; Chronic; Clinical; Clone Cells; Cloning; Collaborations; Communities; Computers; Consultations; Core Facility; Data; Data Set; Databases; Diagnosis; Disease; Disease Progression; Doctor of Philosophy; Dysplasia; Environment; Epithelium; Equipment; Esophageal; Esophageal Adenocarcinoma; Event; Excision; Eye; Facility Accesses; Faculty; Floor; Future; Gene Expression; Genomics; Goals; Grant; Heterogeneity; High-Throughput Nucleotide Sequencing; Home environment; Image; Imaging technology; Incubators; Individual; Institutes; Institution; Investments; Ions; Knowledge; Laboratories; Leadership; Lesion; Libraries; Link; Location; Maintenance; Medical center; Medicine; Methodist Church; Modeling; Molecular; Molecular Biology; Molecular Genetics; Nature; Neoplasm Metastasis; Operative Surgical Procedures; Patients; Pharmaceutical Preparations; Preparation; Preventive therapy; Price; Procedures; Property; Proteomics; Regimen; Regulation; Research; Research Design; Research Institute; Research Personnel; Resected; Resistance; Resources; Role; Safety; Sampling; Services; Source; Stem cells; Students; System; Technology; Telephone; Texas; Therapeutic; Training; Transgenic Animals; Transportation; United States National Academy of Sciences; Universities; Visit; adult stem cell; animal facility; biobank; cancer stem cell; carcinogenesis; chemotherapy; collaborative environment; college; data acquisition; density; drug discovery; epigenomics; experimental study; functional genomics; genetic pedigree; indexing; innovation; instrument; member; next generation sequencing; regenerative; response; senior faculty; square foot; stem cell biology; stem cell technology; tenure track; tissue culture; tumor; tumor heterogeneity; tumorigenesis; undergraduate student; virtual

Contact PD/PI: McKeon, Frank Core-A-001 (004) Project Summary/Abstract: Virtual Biorespository (Core A) The absence of reliable, patient-specific models in cancer biology has been a chronic impediment to understanding heterogeneity, progression, metastasis, and chemotherapy resistance. Recent advances in technologies for cloning adult stem cells resident in normal, regenerative epithelia have been adapted to cloning stem cells from Barrett's esophagus. Investigators in the proposed Center have now extended this technology, in preliminary studies, to cloning the stem cells of dysplastic Barrett's and adenocarcinoma itself. The impact of this technology for resolving key questions in Barrett's and cancer biology in general, including the precise steps in tumorigenesis from precursor lesions, the functional and genomic intra-tumor heterogeneity and its impact on chemotherapy resistance, and lastly the nature and targetability of stem cells of precursor lesions and frank adenocarcinoma, is potentially transformative. As potentially transformative is a biorepository that exploits the regenerative and clonal nature of these stem cells to extend our knowledge of discrete cases in parallel fashion. In Aim 1, we will generate high-density arrays of stem cell clones corresponding to a topological sampling across four mucosal resections of patients with early adenocarcinoma. Aim 2 will generate large libraries of cancer stem cells from advanced cases of esophageal adenocarcinoma. Aim 3 will generate an interactive database that links datasets from both the arrays of clones derived from mucosal resections as well as those associated with analyses of the cancer stem cell libraries. We anticipate that such a virtual database of datasets would greatly augment downstream studies with the same libraries and discrete clones as each would come with such linked datasets that would be further extended by ongoing and future studies by investigators within the Center and across the community. Project Summary/Abstract Page 183 Contact PD/PI: McKeon, Frank Core-A-001 (004) FACILITIES, OTHER RESOURCES Frank McKeon, Ph.D. The University of Houston Scientific Environment: The McKeon lab is located within the Department of Biology and Biochemistry at the University of Houston. The University of Houston is located near to the Texas Medical Center, which is considered the largest medical center in the world. The physical location near to the Texas Medical Center also supports the institution's goal of continual partnership and collaboration with other institutions in the Texas Medical Center (MD Anderson Cancer Center, Baylor College of Medicine, Methodist Research Institute, Texas A&M Institute of Biosciences and Technology and others) by providing easy access to clinical samples and facilities and sharing space and support services. The University of Houston is currently undergoing unprecedented expansion and investment in biomedical research and the life sciences. Nine new tenured and tenure-track faculty have been hired in the Department of Biology and Biochemistry in the last three years, including a member of the National Academy of Sciences, and six of these new hires have been made at the Full Professor level. The University has made commitments to hire eight more tenure and tenure-track faculty into this department over the next three years. The University has also committed $25 million to establish new life science core facilities, including a genomics, proteomics cores, behavioral core laboratory, major upgrades in transgenic animal facilities and the genomics core, and advanced imaging technologies. Moreover, as a member Institution of the Texas Medical Center, University of Houston has equal access to all TMC core facilities and pricing. Furthermore, the Department of Biology and Biochemistry is home to more than 2,000 undergraduate students. These undergraduates can also participate in research and the educational events associated with the Department and Institute. The commitments of the University to biomedical research provide a vigorous and supportive environment for the research proposed in this grant. In addition, Dr. McKeon's leadership role in Center for Stem Cell Biology provides him an opportunity of establishing a crossdisciplinary team for stem cell technology innovation. Laboratory: Dr. McKeon has a laboratory with a floor space of ~2000 square feet including an instrument room equipped with 1 fume hoods, sinks, safety shower and eye-wash station, storage space at 4°C, -20°C, -80°C and desk and bench space for 12 researchers/students, a confined tissue culture room with six biosafety cabinets and eight cell culture incubators, a confined room for Nikon imaging equipment. The lab has been completely renovated and entirely equipped with new equipment. Office PI's office space consists of ~250 square feet (SERC 423) in the in The Department of Biology & Biochemistry and is equipped with telephone, computer and printer. Researcher/student office space is provided inside the laboratory and equipped with telephone, computers, scanner and printers. Animal: The University of Houston provides professional veterinary and husbandry services to support animals used in biomedical and behavioral research, including the maintenance of standards for animals, facilities, equipment, and procedures defined by the governing regulations and accreditation organizations. This is attained by providing such services to the Investigative staff as: animal procurement, training, veterinary consultation in research design, transportation of animals, and veterinary care. Dr. McKeon can also access the Facilities and Service Centers located at The University of Houston: UH NEXTGen Sequencing Center The UH Next Generation Sequencing (NGS) Center is a fully equipped molecular biological laboratory capable of conducting a variety of research tasks in the field of molecular biology and genomics. The high throughput sequencing equipment includes Illumina's NextSeq 500 Sequencer and Thermo Fisher's Ion Torrent PGM sequencer. Additional key equipment includes a OneTouch and OneTouch ES preparation system, Agilent 2100 Bioanalyzer, Biorad T100 thermo cycler, Beckman Coulter Allegra X-°© 15R refrigerated centrifuge, Nuaire Biological Safety Cabinet (Nu-°© 425-°© 500), Misonix Sonicator S-°© 4000, Eppendorf Facilities & Other Resources Page 184

联系 PD/PI：McKeon、Frank Core-A-001 (004) 项目摘要/摘要：虚拟生物仓库（核心 A） 癌症生物学中缺乏可靠的、针对患者的模型一直是癌症生物学研究的长期障碍。 了解异质性、进展、转移和化疗耐药性的最新进展。 用于克隆存在于正常再生上皮细胞中的成体干细胞的技术已适应 拟议中心的研究人员现已扩展了巴雷特食管的克隆干细胞。 在初步研究中，该技术可克隆发育不良巴雷特氏症和腺癌本身的干细胞。 这项技术对解决巴雷特氏病和癌症生物学中的关键问题的影响，包括 前体病变、肿瘤内功能和基因组的肿瘤发生的精确步骤 异质性及其对化疗耐药性的影响，最后是干细胞的性质和靶向性 前体病变和直接腺癌的研究，具有潜在的变革性。 生物储存库利用这些干细胞的再生和克隆性质来扩展我们的知识 在目标 1 中，我们将生成高密度的干细胞克隆阵列。 对应于早期腺癌患者的四次粘膜切除术后的拓扑采样。 目标 2 将从晚期食管腺癌病例中产生大型癌症干细胞文库。 目标 3 将生成一个交互式数据库，该数据库链接来自派生的克隆阵列的数据集 我们预计粘膜切除术以及与癌症干细胞库分析相关的手术。 这种数据集的虚拟数据库将极大地增强使用相同库的下游研究 离散的克隆，因为每个克隆都带有这样的链接数据集，这些数据集将通过持续和持续的进一步扩展 中心和整个社区的研究人员未来的研究。 项目摘要/摘要第 183 页 联系 PD/PI：McKeon、Frank Core-A-001 (004) 设施、其他资源 弗兰克·麦肯博士 休斯敦大学 科学环境： 麦肯实验室位于休斯顿大学生物与生物化学系。 休斯顿大学位于德克萨斯医学中心附近，该中心被认为是最大的医学中心 靠近德克萨斯医学中心的物理位置也支持该机构的目标。 与德克萨斯医学中心（MD 安德森）其他机构的持续伙伴关系和协作 癌症中心、贝勒医学院、卫理公会研究所、德克萨斯 A&M 生物科学研究所 和技术等）通过提供轻松访问临床样本和设施以及共享空间和 休斯顿大学目前正在进行前所未有的扩张和投资。 生物医学研究和生命科学领域聘用了九名新的终身教授和终身教授。 过去三年的生物和生物化学系，包括美国国家科学院院士 科学学院聘用了六名新员工，其中六名是正教授级别的。 承诺在未来三年内再聘请八名终身教授和终身教授进入该系。 该大学还投入 2500 万美元建立新的生命科学核心设施，包括基因组学、 蛋白质组学核心、行为核心实验室、转基因动物设施和基因组学的重大升级 此外，作为德克萨斯医学中心的成员机构， 休斯顿大学可以平等使用所有 TMC 核心设施和定价。 生物学和生物化学专业有超过 2,000 名本科生。 还参加与部门和研究所相关的研究和教育活动。 大学对生物医学研究的承诺为生物医学研究提供了一个充满活力和支持的环境 此外，McKeon 博士在干细胞生物学中心的领导作用。 为他提供了建立干细胞技术创新跨学科团队的机会。 实验室： McKeon 博士拥有一个占地约 2000 平方英尺的实验室，其中包括一间配备了设备的仪器室 配有 1 个通风柜、水槽、安全淋浴和洗眼站、4°C、-20°C、-80°C 的存储空间和办公桌 以及可容纳 12 名研究人员/学生的工作台空间、一间配有 6 个生物安全柜的密闭组织培养室以及 八个细胞培养箱、一间用于尼康成像设备的密闭室实验室已完全建成。 翻新并完全配备新设备。 办公室 PI 生物与生物化学系的办公空间约为 250 平方英尺（SERC 423） 并配备电话、电脑和打印机等研究员/学生办公空间。 实验室并配备电话、电脑、扫描仪和打印机。 动物： 休斯顿大学提供专业的兽医和饲养服务，以支持用于 生物医学和行为研究，包括维持动物、设施、设备的标准， 管理和法规认证组织定义的程序和程序是通过以下方式实现的。 为调查人员提供以下服务：动物采购、培训、兽医咨询 研究设计、动物运输和兽医护理。 McKeon 博士还可以访问休斯顿大学的设施和服务中心： 呃 NEXTGen 测序中心 夏威夷大学下一代测序 (NGS) 中心是一个设备齐全的分子生物实验室，能够 在分子生物学和基因组学领域开展各种研究任务。 测序设备包括 Illumina 的 NextSeq 500 测序仪和 Thermo Fisher 的 Ion Torrent PGM 其他关键设备包括 OneTouch 和 OneTouch ES 制备系统、Agilent。 2100 生物分析仪、Biorad T100 热循环仪、Beckman Coulter Allegra X-°© 15R 冷冻离心机、 Nuaire 生物安全柜 (Nu-°© 425-°© 500)、Misonix Sonicator S-°© 4000、Eppendorf 设施和其他资源 第 184 页