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Biorespository（核心A） 癌症生物学中缺乏可靠的，患者特异性的模型一直是慢性障碍 了解异质性，进展，转移和化学疗法抗性。最近的进步 在正常，再生上皮中克隆成年干细胞居民克隆的技术已适应 从巴雷特的食道来克隆干细胞。拟议中心的调查人员现已扩展了这一点 在初步研究中，技术来克隆发育不良的Barrett和腺癌本身的干细胞。 这项技术对解决巴雷特和癌症生物学的关键问题的影响，包括 前体病变（功能性和基因组内）肿瘤发生的精确步骤 异质性及其对化学疗法抗性的影响，最后是干细胞的性质和目标性 前体病变和坦率的腺癌具有可能性的变化。因为潜在的变革是 利用这些干细胞的再生性和克隆性质的生物座位，以扩展我们对 平行方式离散案例。在AIM 1中，我们将生成高密度的干细胞克隆 对应于早期腺癌患者的四个粘膜切除术进行拓扑采样。 AIM 2将产生大量的食管腺癌病例的癌症干细胞。 AIM 3将生成一个交互式数据库，该数据库链接来自两个来自来自的克隆阵列的数据集 粘膜切除术以及与癌症干细胞库分析相关的粘膜切除术。我们期待 这样的数据集的虚拟数据库将大大增加与同一库的下游研究 离散克隆，每个都将带有此类链接数据集，这些数据集将通过持续和 中心和整个社区的研究人员的未来研究。 项目摘要/摘要页面183 联系PD/PI：McKeon，Frank Core-A-001（004） 设施，其他资源 弗兰克·麦基恩（Frank McKeon）博士 休斯顿大学 科学环境： 麦肯实验室位于休斯顿大学生物学和生物化学系内。 休斯顿大学位于德克萨斯医疗中心附近，该中心被认为是最大的医疗 世界中心。得克萨斯州医疗中心附近的物理位置也支持该机构的目标 与德克萨斯医学中心（MD Anderson的其他机构）的持续合作和合作 贝勒医学院癌症中心，德克萨斯州A＆M生物科学研究所卫理公会研究所 和技术等）通过轻松访问临床样本和设施以及共享空间以及 支持服务。休斯顿大学目前正在进行前所未有的扩张和投资 在生物医学研究和生命科学中。在 在过去三年中，生物学和生物化学系，包括国家学院的成员 在整个教授级别上，科学和其中六名新员工已成为。大学做了 承诺在未来三年内再聘请八个任期和任期教师进入该部门。 该大学还承诺了2500万美元来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，转基因动物设施的重大升级和基因组学 核心和高级成像技术。此外，作为德克萨斯州医疗中心的会员机构， 休斯顿大学可以平等地使用所有TMC核心设施和定价。此外，部门 生物学和生物化学是2,000多名本科生的所在地。这些本科生可以 还参与了与部门和研究所相关的研究和教育活动。这 大学对生物医学研究的承诺为 这笔赠款提出的研究。此外，麦基恩博士在干细胞生物学中心的领导角色 为他提供了建立一个跨学科团队进行干细胞技术创新的机会。 实验室： McKeon博士拥有一个实验室，地板空间约为2000平方英尺，包括配备的仪表室 带有1个烟雾罩，水槽，安全淋浴和眼睛洗牌站，4°C，-20°C，-80°C和桌子的存储空间 和板凳空间，可容纳12位研究人员/学生，一个有限的组织培养室，设有六个生物安全橱柜和 八个细胞培养孵化器，这是尼康成像设备的限制空间。实验室已经完全 翻新并完全配备了新设备。 办公室 PI的办公空间由生物学与生物化学系中的约250平方英尺（SERC 423）组成 并且等效于电话，计算机和打印机。研究人员/学生办公空间在内部提供 实验室并配备电话，计算机，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，以支持使用的动物 生物医学和行为研究，包括维护动物，设施，设备， 以及管理法规和认证组织定义的程序。这是由 向调查人员提供此类服务，例如：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： UH NextGen测序中心 UH下一代测序（NGS）中心是一个设备齐全的分子生物实验室 在分子生物学和基因组学领域中执行各种研究任务。高吞吐量 测序设备包括Illumina的NextSeq 500 Suequencer和Thermo Fisher的离子Torrent PGM 音序器。其他关键设备包括一个OneTouch和OneTouch ES准备系统，Agilent 2100 BioAnalyzer，Biorad T100 Thermocycler，Beckman Coulter Allegra X-°©15R冷藏离心机， Nuaire生物安全柜（Nu-°©425-°©500），Misonix Sonicator S-°©4000，Eppendorf 设施和其他资源第184页