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 4C, -20C, -80C 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