CAMPUS THEORY SEMINAR
               Part of the SCIENCE AT THE EDGE Seminar Series

                           Friday, May 4, 2001
                           11:30am, Room 224 PA

                         Refreshments at 11:15am

        Integrating Genomics and Proteomics in the Post-Genome Era

            S.M. Hanash, University of Michigan Medical Center
                           Ann Arbor MI 48109
                       e-mail shanash@umich.edu

The dawn of the post-genome era is leading to extraordinary opportunities
in biomedicine. Our group has embarked on a major effort to integrate
genomics transcriptomics and proteomics for the profiling of cancer tissue,
an approach we refer to as Operomics. Our major goals are the molecular
classification of tumors and the identification of markers for the early
detection of cancer.  Molecular analyses of tumors rely on microdissected
tissues which are simultaneously investigated for genomic, transcriptomic
and proteomic changes. Genomic alterations in tumor cells being
investigated include deletions, amplifications and methylation changes
across the entire genome. Expression analysis at the RNA level is being
undertaken using oligonucleotide and cDNA based microarrays. An important
aspect of our approach is the large scale identification and quantitative
analysis of tumor proteins in whole cell lysates as well as in protein
compartments. Separation strategies include 2-D (2-D) electrophoresis,
liquid chromatography (LC) and a 2-D/LC combination. Specific protein
subsets of interest include secreted proteins, antigenic proteins and
membrane proteins as a source of biomarkers for early detection of cancer.
In the first phase of the proteomic analysis, a database of more than 1,000
identified proteins for each tumor type is being constructed that includes
for these proteins their quantitative level and known post-translational
modification(s), their spot matching in a hierarchy of 2-D images, the
level of their corresponding RNAs and the status of their genes from a gene
dosage and methylation points of view. The approach we have developed is
equally applicable to other disease states and to model organisms.