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2002 Scientific Report

  • Text
  • Institute
  • Report
  • Tumors
  • Protein
  • Signaling
  • Michigan
  • Molecular
  • Proteins
  • Laboratory

studying the protein

studying the protein alterations in the sera of pancreatic cancer patients. Microarray core facility The DNA microarray is widely regarded as a revolutionary technology in biological research. Since its introduction about 10 years ago, microarrays have grown in use and usefulness and have contributed to many significant discoveries. VARI’s microarray core facility makes this technology accessible and useful to its researchers and to external collaborators. We have acquired sets of 40,000 human cDNA clones, 15,000 mouse cDNA clones, and through our collaboration with the Core Technology Alliance of the Michigan Life Sciences Corridor, 20,000 rat cDNA clones. A high-throughput liquid-handling robot is used to prepare these DNA sequences for microarrays, and a robotic arrayer spots the DNAs at high density onto the surfaces of glass slides (about 20,000 spots in 2 × 4 cm). The high-density spotting of DNA sequences allows simultaneous hybridization assays on thousands of genes. Rigorous quality control at every level of the microarray production and use has allowed us to routinely generate high-quality data, and more than 1,000 microarray experiments will have been performed at VARI in the year 2002. The core facility provides training in the use and analysis of microarrays and access to the latest analysis tools. Support from VARI bioinformaticians Kyle Furge and Edward Dere, along with a new microarray database built by the Information Technology department at VARI, provides extensive informatics capability for microarray users. The core is also involved in technology and methods development. New arrays are being produced that comprise only sequences from verified and named genes, or sequences pertaining to particular projects. Focused gene sets allow replicate spotting of each sequence and better verification of the quality of each sequence. Arrays made from sets of 70-base oligonucleotides, which may provide reduced cross-reactivity with other genes relative to cDNA clones, are being validated and characterized to complement our existing cDNA arrays. In addition, we are implementing methods of signal amplification to allow detection of low quantities of RNA. Applications of DNA microarrays include the study of the mRNA expression patterns in human tumor samples and the study of changes in cell-line gene expression after perturbations. The data are analyzed to identify genes that statistically correlate with other genes, phenotypes, clinical parameters, disease states, or perturbation states. A detailed analysis of gene expression programs can yield insight into the function and interrelationship of genes and can suggest strategies of intervention in disease. Many VARI researchers, as well as external researchers, are making use of VARI’s microarray facility for such studies. External Collaborators Phil Andrews, Samir Hanash, and Gil Omenn, University of Michigan, Ann Arbor Jose Costa and Paul Lizardi, Yale University School of Medicine, New Haven, Connecticut Yi Ren, University of Hong Kong Anthony Schaeffer and John Grayhack, Northwestern University, Evanston, Illinois Peter Schirmacher, University of Cologne, Germany Bin S. Teh, Baylor College of Medicine, Houston, Texas Cornelius Verweij, University of Amsterdam, The Netherlands Tim Zacharewski, Michigan State University, Lansing 29

Publications Haddad, Ramsi, Kyle A. Furge, Jeremy C. Miller, Brian B. Haab, J. Schoumans, Bin T. Teh, L. Barr, and Craig P. Webb. In press. Genomic profiling and cDNA microarray analysis of human colon adenocarcinoma and associated intraperitoneal metastases reveals consistent cytogenetic and transcriptional aberrations associated with progression of multiple metastases. Applied Genomics and Proteomics. Miller, Jeremy C., E. Brian Butler, Bin S. Teh, and Brian B. Haab. 2001. The application of protein microarrays to serum diagnostics: prostate cancer as a test case. Disease Markers 17(4): 225–234. Miller, Jeremy C., Heping Zhou, Joshua Kwekel, Robert Cavallo, Jocelyn Burke, E. Brian Butler, Bin S. Teh, and Brian B. Haab. In press. Antibody microarray profiling of human prostate cancer sera: antibody screening and identification of potential biomarkers. Proteomics. Rhodes, Daniel R., Jeremy C. Miller, Brian B. Haab, and Kyle A. Furge. 2002. CIT: identification of differentially expressed clusters of genes from microarray data. Bioinformatics 18(1): 205–206. Robinson, William H., Carla DiGennaro, Wolfgang Hueber, Brian B. Haab, Makoto Kamachi, Erik J. Dean, Sylvie Fournel, Derek Fong, Mark C. Genovese, Henry E. Neuman de Vegvar, Gunter Steiner, David L. Hirschberg, Sylviane Muller, Ger J. Pruijn, Walther J. van Venrooij, Josef S. Smolen, Patrick O. Brown, Lawrence Steinman, and Paul J. Utz. 2002. Autoantigen microarrays for multiplex characterization of autoantibody responses. Nature Medicine 8(3): 295–301. From left to right, back row: Haak, Kwekel, Vreder, Diephouse, Schotanus front row: Norton, Zhou, Kaledas, Haddad, Haab 30

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