Genitourinary Cancer Research Laboratory
Directors
Paul H. Lange, MD
Professor and Department Chairman
(206) 543 1461
Robert L. Vessella, PhD
Pritt Family Chair in Translational Prostate Cancer Research
Professor and Department Vice-Chair
(206) 543 1463
Eva Corey, PhD
Associate Professor
(206) 543 0788
Colm Morrissey, PhD
Acting Assistant Professor
cmorriss@u.washington.edu
Fax: (206) 543 1146
Postal Address:
Department of Urology
Mailstop 356510
University of Washington Seattle, 98195, USA
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Research Interests
The Genitourinary Cancer Research Laboratory has been active at the University of Washington since its move from the University of Minnesota in July, 1989. The laboratory has been directed by Paul Lange, MD, and Robert Vessella, PhD since its inception in 1976. More recently, Eva Corey, PhD has joined as a co-director. This laboratory comprises one of the department’s research Centers of Excellence where physicians and scientists combine efforts toward a common goal.
In addition to the leadership of Drs. Lange, Vessella and Corey, the laboratory consists of approximately 12 full time technical staff, 3 post-doctoral fellows, 1 Urology resident in his research year and 20 part-time undergraduate students. The full time personnel are listed in the table that follows.
Since the early 1990’s the primary research efforts have been directed toward prostate cancer with a more recent specific interest in prostate cancer bone metastasis.
The laboratories are organized into four components:
- Detection, Isolation and Characterization of Disseminated Prostate Cancer Cells
- Biology of Prostate Cancer Bone Metastases
- Biospecimen Acquisition
- Prostate Cancer Xenograft Generation
Detection, Isolation and Characterization of Disseminated Prostate Cancer Cells
All metastases evolve from the dissemination of tumor cells from their primary organ but not all of the disseminated tumor cells result in a clinically relevant metastasis. The study of disseminated prostate cancer cells began in 1992 and continues to the present. This is a fascinating field of study that has tremendous clinical implications. In collaboration with investigators at the Fred Hutchinson Cancer Research Center we are currently engaged in state-of-the-art studies to characterize disseminated tumor cells isolated from the bone marrow of patients at the time of radical prostatectomy and through-out their long term follow-up. We are also focusing on studies to investigate dormancy of the disseminated tumor cells.
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Biology of Prostate Cancer Bone Metastases
Bone is the second most frequent site of prostate cancer metastases. Once the disseminated prostate cancer cells seed the bone marrow, there is a complex process of adaptation and growth that is poorly understood. In addition, during the process of tumor growth, the prostate cancer cells secrete factors that perturb the normal bone remodeling causing new bone formation and leading to development of the osteoblastic reaction in the bone. We are engaged in studies to understand these processes. Our research focuses on Identification the key factor involved, e.g., osteoprotegerin, and bone morphogenetic proteins. We are also performing studies to evaluate novel therapeutic strategies for bone metastases.
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Biospecimen Acquisition
Since its inception, there has been a significant effort to build a biospecimen repository for genitourinary cancers. This repository consists of serum and tissue samples. Over the past several years this has been expanded to include plasma and lymphocytic DNA. All of the specimens are cross referenced to the patient’s clinical status and there is an extensive number of serial serum specimens from patients returning to the clinic for follow-up. Tissue specimens are primarily collected from the operating room. Since it is nearly impossible to obtain prostate cancer bone or non-bone distant organ metastases from surgical interventions, we developed the rapid autopsy program in 1991. With the great assistance of Medical Oncology, patients who are terminal with advanced prostate cancer are consented to participate in this program. A pathologist, a urology resident and five members of the research laboratory perform an autopsy commencing within 2–3 hours of death. Metastases and control tissues are acquired and immediately processed. Most importantly, twenty specific bone sites are acquired for our studies of bone metastases. These specimens are invaluable for understanding the biology and complexity of this process. Approximately 8 – 10 rapid autopsies are performed per year. Our biospecimens are shared with investigators world-wide.
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Prostate Cancer Xenograft Generation
Using primary tumors and metastatic tissues, we have established 21 long term, stable xenografts which are serially passaged (success rate of approximately 18%). These xenografts represent the complexity of the disease seen in man and offer significant opportunities for studying specific features of interest. For example, the LuCaP 23.1 prostate cancer xenograft causes the characteristically robust osteoblastic response seen upon prostate cancer growth in man and the LuCaP 35 xenograft most clearly represents the progression from androgen dependence to androgen independence. These xenografts, like our biospecimens, are used extensively in our own studies and shared with investigators world wide.
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Laboratory Resources
With over 2500 sq ft of research space, our modern laboratory includes facilities for biospecimen processing, human cell culture, molecular biology, histology, protein chemistry and animal studies.
Human Tissue Culture Facility and Human Tissue Processing
This room is dedicated to the processing of human tissue for cell culture, molecular biology and histology. It is equipped with a laminar flow biological cabinet and two incubators for tissue culture, as well as a large-capacity liquid nitrogen freezer. There is an inverted microscope for tissue culture and a photomicroscopy system for histology. The room also contains a standard fume hood. For tissue processing there is a microtome, Histobath low-temperature freezing system and a cryostat. There is an assortment of centrifuges and pH meters and other standard laboratory equipment.
Biospecimen Specimen Storage
The laboratory has nine ultra-low temperature freezers for the assortment of biospecimens collected and stored by the laboratory.
Molecular Biology and Protein Chemistry Facility
This multi-room facility is equipped with 4 cDNA thermal cyclers, and RotorGene real-time PCR machine. Among other major items are a large number of electrophoretic systems, a plate spectrophotometer, luminometer and flurorimeter, three untracentrifuges, a small autoclave, and a hybridization oven. This area also contains a large miscellany of small equipment (e.g., water baths, pH meters, scales). There is also an Alpha Innotech Imaging system for gel analyses.
Automated Immunoassay Facility
The laboratory has an automated Abbott IMx immunoassay system, typically used for PSA and free-PSA research assays.
SPF Athymic Mouse and SCID Mouse Facility
The SPF animal facility is a suite of five rooms adjacent to the research laboratories which house ~1100 immune compromised mice. Access is highly restricted. The facility is routinely inspected and certified by the IACUC and the Department of Comparative Medicine. Most studies undertaken in the facility involve serially passaged prostate cancer xenografts developed by the laboratory. The animal facility is equipped with a Faxitron X-ray system and a Piximus densitometer. There is also additional small equipment to support animal studies.
Computer Facility
All of the GU Cancer Research Laboratory, as described above, is connected to a Windows server which provides all standard applications (e.g.,Word, Excel, Photoshop, Refman) and is used in maintaining the Tissue sand Serum Banks. There are 13 workstations interspersed through the laboratories that access this server. The server is connected to the UW mainframe systems and the internet.
Histomorphometry Analysis Equipment
For bone histomorphometry, GU Cancer Laboratory is equipped with a microtome for cutting plastic sections and mineralized bones, and Bioquant Analysis System equipped with digital camera and computer for data processing.
Computer and Other
The core facility of the Microbiology Department is available (warm room, electroporation apparatus, phosphoimaging system, dark room, etc.) as is the extensive computer network of the University of Washington. Resources at the University of Washington also include a large medical library and medical illustration and photography services.
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Lab Members:
| Name | Degree | ||
|---|---|---|---|
Faculty |
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| Corey | Eva | PhD | ecorey@u.washington.edu |
| Vessella | Robert | PhD | vessella@u.washington.edu |
Administrative Coordinator |
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| Chong | Jae | Bachelors | jjc5@u.washington.edu |
Senior Fellows |
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| Lai | Janice | PhD | laij@u.washington.edu |
| Sun | Xizhang | PhD | sunx@u.washington.edu |
| Research Scientists |
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| Baldwin | Michael | Bachelors | actaeon@u.washington.edu |
| Brown | Lisha | Bachelors | brown@u.washington.edu |
| Gallagher | Ian | Bachelors | iansg@u.washington.edu |
| Gonzales | Deanna | Bachelors | deanng@u.washington.edu |
| Kinnunen | Marty | Bachelors | emo95@u.washington.edu |
| Lakely | Bryce | Bachelors | brycel@u.washington.edu |
| LaVoie | Nicole | Bachelors | ncl2@u.washington.edu |
| Noteboom | Jennifer | Bachelors | noteboom@u.washington.edu |
| Pitts | Tiffany | Bachelors | tes4@u.washington.edu |
| VanMason | Adam | Bachelors | vanmaa@u.washington.edu |
| Wang | Christine | Bachelors | cwang2@u.washington.edu |
| Research Study Assistant |
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| Blanchette | Christina | Bachelors | cblanche@u.washington.edu |
Research Technician |
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| Dalos | Michiyo | A.A. | michan@u.washington.edu |
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