Administrative Core
Dr. Warren Ladiges,
DVM, Professor, Department of Comparative Medicine is Principal Investigator.
He is currently Director of the Transgenic Resources Program at the University
of Washington. He has had a longstanding interest in tumor biology in animal model
systems including murine breast cancer, feline leukemia and canine lymphoma. He
worked for six years with Nobel Laureate E. Donnel Thomas, and Dr. Rainer Storb
in the Transplantation Biology Program at the Fred Hutchinson Cancer Research
Center. While there, part of his responsibilities included managing the congenic
and inbred mouse breeding colonies. He has experience with core resources since
1986 when the Antibody Resource Laboratory began operation for the School of Medicine
at the University of Washington. In 1995, he started the Transgenic Resources
Program as a result of funding from NIA and NIEHS program projects, serving as
principle investigator of each respective transgenic core resource service. Because
of the huge demand for services from other University of Washington scientists,
a cost center for recharges was started in 1998. Dr. Ladiges has had extensive
transgenic mouse modeling and mouse genetics experience, and extensive, in-depth
expertise in the pathobiology of transgenic mouse models as they relate to human
disease. His career as an independent scientist has been recognized by his peers
in the approval of an NIH Mid-career Research Award in Mouse Pathobiology Research.
Heather Hopkins, B.A., to supervise the administrative activities of the proposed Center. This will be a key position working closely with the Principal Investigator for the planning, coordinating and implementing of all administrative functions required. This position will interact directly with the PI, co-PI, other Consortium personnel, and NIEHS staff personnel, to carry out the infrastructure responsibilities. The position, with office space in the Department of Comparative Medicine, will report directly to the PI and be responsible for fiscal and resource management, coordinating the transition of administrative information among the various research lab components, and the transfer of new technology and mouse models by interacting with the Office of Technology Transfer at the University of Washington. Additional responsibilities will include interacting with bioinformatics personnel and other Consortium groups, as well as with program officials at NIEHS.
Mouse Model Development
Dr. Chris Kemp, Ph.D., Associate Member, Fred Hutchinson Cancer Research Center and Affiliate Associate Professor, Department of Pathology, University of Washington, is co-Principal Investigator. He will be responsible for leadership and guidance in the scientific focus of the grant. His activities, expertise and contributions to the scientific accomplishments of the proposal will be significant, and are described in the FHCRC subcontract in the appendix.
Dr. Lawrence Loeb, MD, Ph.D., Professor, Departments of Pathology and Biochemistry, and Director, Joseph Gottstein Memorial Cancer Research Laboratory, University of Washington, is a key scientist participating in this proposal, and has extensive expertise in enzymology of DNA replication and repair. He has extensively published in the area of cancer, DNA damage, mutation, and DNA repair. He originally suggested the hypothesis that cancer is manifested by a mutator phenotype, based on the argument that the spontaneous mutation rate in normal cells is insufficient to account for the high frequency of mutations in human cancer cell. He has an extensive record of publications in this area and is PI on a number of NIH funded research grants. He and his laboratory have the expertise and technical capabilities of working with DNA repair genes and performing the critical in vitro functional analyses.
Dr. Eitan Glick, Ph.D, Postdoctoral Research Fellow, will work in Dr. Loeb’s laboratory to design and execute in vitro biochemical assays for DNA repair genes and for DNA polymerases/helicases. Dr Glick will then compare the variant enzyme function with the wild type function to determine whether generating a mouse model of the gene variant is beneficial to the project.
Dr. Maynard Olson, PhD, Professor, Department of Medicine and Adjunct Professor, Department of Computer Science, is Director of the University of Washington Genome Center and PI on three major grants that support the UWGC’s activities. 1) A large core grant funded through the National Human Genome Research Insititute for sequence portions of the human genome; 2) a grant funded through the NIEHS that is focused on characterizing natural variation in human genes that are known to play an important role in modulating effects on human biology; and 3) a grant jointly funded by the Cystic Fibrosis Foundation and PathoGenesis, Inc., to sequence the 6-Mbp genome of the opportunistic human pathogen Pseudomonas aeruginosa and to charaterize genetic variation in clinical islolates of Pseudomonas. Total cost support for the UWGC has been in the range of $6-8 million per year during recent years. The UWGC maintains a diversified capability to clone, map, sequence, and annotate genomic DNA from any organism. A major thematic interest in the Center is to apply large-scale analysis tools to identify functionally important sequence variation in genomes that reflect adaptation to specific environments. He will be responsible for overseeing the resequencing of DNA repair/cell cycle control genes for identifying single nucleotide polymorphisms that will be used to generate mutant mice in this proposal.
Dr. Gane Wong, PhD , Research Scientist, Department of Medicine, works at the University of Washington Genome Center and has a dedicated effort in the NIEHS-funded SNP discovery project. He is responsible for much of the administrative and data collection and presentation aspects of this project and will interact directly in this proposal to coordinate dissemination of data from resequencing DNA repair/cell cycle control genes.
Dr. Jun Yu, Ph.D, Research Scientist, Department of Medicine, also works at the University of Washington Genome Center and has a dedicated effort in the NIEHS-funded SNP discovery project. He is responsible for coordinating the technical aspects of gene resequencing and the depth of sample testing. He will interact directly in this proposal to coordinate the resequencing of DNA repair/cell cycle control genes on the appropriate sample background.
Dr. Ruth Wilson, Ph.D., Research Scientist, Department of Comparative Medicine, She will be responsible for designing DNA constructs from the homologous mouse gene variants to generate transgenic mouse models. Once the construct is complete, she will insert it (knock-in) into mouse embryonic stem cells for future microinjection.
Dr. Carol Ware, Ph.D, Assistant Professor Department of Comparative Medicine, has expertise in the biology and targeting of mouse ES cells.
John Morton, B.S., Research Scientist, Department of Comparative Medicine, , will perform the actual ES cell targeting , cloning, and develop ES cell lines, including null lines, for dissemination to other consortium members, and interested scientists as appropriate. He will also prepare mouse samples for DNA microarray analysis.
Dr. Charsa Ailes, DVM, Senior Fellow, Department of Comparative Medicine. She will be responsible for supervising the research and health management of the transgenic mouse colony.
Ruby Mangalindan, (DVM degree from the Philipines), Research Technologist I. She will perform the day to day colony breeding and monitor all mice on experiments challenged with ENU or irradiation. She will work closely with the research veterinarian.
Dr. Denny Liggitt, DVM, Ph.D, Professor, Department of Comparative Medicine, is a board certified veterinary pathologist with extensive experience in the pathobiology of genetically altered mouse models. He will be responsible for the overall assessment of pathological lesions in the mouse lines in this proposal.
Dr. Peter Rabinovitch, MD, Ph.D, Professor, Department of Pathology, is Director of the Flow Cytometry Imaging Resources at the University of Washington, and has a long and productive history of cytometric analysis of mouse cells and tissues associated with the molecular biology of tumorigenesis and aging.
New Technologies
Dr. Christophe Verlinde, Ph.D., Associate Professor, Department of Biological Structure has experience with macromolecular modeling for the past 5 years. He will be replacing Dr. Ellie Adman who is retiring this year and was originally listed as a Co-Investigator on this grant. His participation on the projects of the center has already begun. He will be responsible for assessment of macromolecular structure/function of DNA repair/cell cyle control SNP variants identified in this proposal.
Dr. Kenneth Krohn, Ph.D., Professor, Department of Radiology, is a nuclear chemist who has directed the UW's effort in positron emission tomagraphy (PET) since 1981. He is P.I. of the only NIH program project grant which supports PET oncology research, a grant continuously funded since 1986. Dr. Krohn is a fellow of the AAAS and won the Aebersold Prize from the Society of Nuclear Medicine in 1997 in recognition of his international stature in the field of nuclear medicine. Dr. Krohn's group developed and/or improved the syntheses of [F-18]FMISO, [C-11] thymidine (TdR; labeled in the pyrimidine ring, thereby producing fewer labeled metabolites than does labeling in the methyl position), and [F-18]fluoroestradiol, an estrogen analog. He will be responsible for overseeing the radiotracer development and PET imaging objectives of the proposal.
Dr. Svetlana Stekhova, Ph.D., is an organic chemist who has worked in Krohn’s laboratory since 1997 and will be the principal individual involved in making the specific imaging probe molecules to be used in this study. She has previous experience in synthesis of positron-emitter labeled steroids, receptor ligands and therapeutic drugs as imaging agents.
Dr. Kevin Yagle, Ph.D., is a molecular biologist who has recently joined Krohn’s group to evaluate the biochemical mechanisms of uptake of specific radiolabeled tracers used for molecular imaging of cancer, diabetes and neurodegenerative disorders. His role will be in the pre-animal testing of new probes using binding assays and cellular studies and in mouse studies that involve histology, optical imaging of tissue slices, and other invasive procedures.
Bioinformatics
Jesse C Wiley, BS; bioinformatics lead.
Manjula Prattipati, MS; technology development lead.
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Last
Updated:
24 May, 2002
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