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2004 Scientific Report

tissues from specific

tissues from specific West Michigan hospitals. This HIPAA-approved program involves the active collaboration of surgeons and pathologists. This material is used primarily in cDNA and Affymetrix gene expression studies and discovery. Surgically removed human tumors and normal tissue are evaluated in IRB-approved basic and translational research projects. This collection will at the same time provide the participating physicians with access to research collaborations, with the intention of facilitating the translation of research results into clinical practice. We plan to generate gene expression profiles (microarray), establish new tumor cell lines, and develop new diagnostic and therapeutic agents through these collaborations. Epidemiologic evaluations will also be greatly improved by the coordination of clinical information, diagnosis, and research results. The goal of this project is to develop genetics-based diagnostic classification of human disease. There is a Scientific Advisory Board for this project comprising members of VARI and of the Spectrum Health pathology, surgical and medical oncology, and surgery departments. Tissue is collected with explicit written permission of the participating patients and physicians. Protocols for the use of the material in this archive require the approval of both the VARI and the Spectrum Health IRBs. In the last three calendar years, under our histology and pathology service program, we have processed 925 requests for histopathologic services that required 8,650 blocks and more than 48,000 glass slides. We have prepared over 107,000 digital images of this material and all are available on network servers to expedite their use by the research staff and external collaborators. We have provided tissue and histopathology services to 12 VARI investigators and have generated over 72,000 microscopic images and related files for the collaborations. The MD lab is preparing gene expression data from cells and tissues and is correlating that with histology, tissue volume, and nuclear density to determine an effective and accurate screen for quality of analysis. We are evaluating a series of cases to determine the features that define a “quality specimen.” We also focus on quantification of images and the development of objective measureable data from images. Kort et al.’s Cytometry paper in 2003 was our first report of a software program to quantify scattering. This is important in the development of drugs and interventions to control the branching, differentiation, and metastatic processes that are crucial in both normal and pathophysiology. We have recently obtained NIH funding for a major effort in multiphoton imaging of developmental and carcinogenic events in GFP-expressing transgenic mice in collaboration with George Vande Woude, Ilan Tsarfaty, and Rick Hay. This project and others will evaluate the role of Met and HGF/SF in branching morphogenesis, carcinogenesis, and therapy. Other collaborations within VARI involve Met and HGF/SF in cells and tissues; the location of gene-targeted proteins in rodents; evaluation of monoclonal antibodies as diagnostic reagents; and the cellular and subcellular localization and quantification of proteins. Together with Grand Valley State University and Grand Rapids Community College, we have received NIH funding as part of the Bridges to the Baccalaureate program to support the recruitment of women and minorities into science careers. Dr. Resau is a co-investigator and site coordinator for the Bridges program. We have established an innovative program for public school students in Grand Rapids and have had a mentorship program funded by Pfizer for the past four years. Twelve high school students have trained in the laboratory and are now in baccalaureate programs. This program has recently been recognized by the Grand Rapids public school system and will be developed as a “school-within-aschool” program at Creston High School. This is a partnership between GRAPCEP, GVSU, and VARI and is directed by Davenport University. External Collaborators Greg Taylor, University of North Carolina, Chapel Hill Ernst Lengyel, University of Chicago, Illinois Eric Arnoys, Calvin College, Grand Rapids, Michigan Lonson Barr, Michigan State University, East Lansing Maria Roberts, National Cancer Institute, Frederick, Maryland 40

Christine Hughes, Harvard University, Cambridge, Massachusetts O. Orit Rosen, Harvard University, Cambridge, Massachusetts Josh Webster, Michigan State University, East Lansing Matti Koeppel, Michigan State University, East Lansing Stephan Baldus, University of Cologne, Germany D. Cowen, University of North Carolina, Chapel Hill Nadia Harbeck, Ludwig-Maximilians-Universität, Munich, Germany Kristina Lindemann, Munich, Germany Ilan Tsarfaty, Tel Aviv University, Israel Iafa Keydar, Tel Aviv University, Israel John Sacci, University of Maryland, Baltimore John Ubels, Calvin College, Grand Rapids, Michigan Recent Publications Hay, Rick V., Brian Cao, R. Scot Skinner, Ling-Mei Wang, Yanli Su, James H. Resau, Beatrice S. Knudsen, Margaret F. Gustafson, Han-Mo Koo, George F. Vande Woude, and Milton D. Gross. 2003. Radioimmunoscintigraphy of human Met-expressing tumor xenografts using Met3, a new monoclonal antibody. Clinical Cancer Research 9(10): 3839S–3844S. Kort, Eric J., Bryon Campbell, and James H. Resau. 2003. A human tissue and data resource: an overview of opportunities, challenges, and development of a provider/researcher partnership model. Computer Methods and Programs in Biomedicine 70(2): 137–150. Kort, Eric J., Ashley Jones, Michael Daumbach, Eric A. Hudson, Bree Buckner, and James H. Resau. 2003. Quantifying cell scattering: the blob algorithm revisited. Cytometry 51A(2): 119–126. Hay, Rick, Brian Cao, Ilan Tsarfaty, Galia Tsarfaty, James Resau, and George Vande Woude. 2002. Grappling with metastatic risk: bringing molecular imaging of Met expression toward clinical use. Journal of Cellular Biochemistry S39: 184–193. Along window, top to bottom: Leeser, Resau, Goolsby, Haak, Norton, Hudson; left, top to bottom: Sigler, Buckner 41

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