02 July 2013, 16:15
Carl-Zeiss-Str. 3, seminar room 309

Analyzing the regulation of tumor metabolism

Prof. Dr. Rainer König  (Center for Sepsis Control and Care (CSCC); Group: Network Modeling)

Metabolism is the functional phenotype of a cell, at a given condition, resulting from an intricate interplay of various regulatory processes. Metabolic deregulation is an emerging hallmark of cancer cells. This deregulation results in rewiring of the metabolic circuitry conferring an exploitative metabolic advantage for the tumor cells which leads to a distinct benefit in survival and lays the basis for unbound progression. Gene expression profiling by microarrays or transcript sequencing enables observing the pathogenic function of tumors on a mesoscopic level. We investigate the regulation of metabolism of several tumors including glioblastomas and neuroblastomas showing clinically distinct courses. To get a comprehensive insight into the aberrant regulation of the different biochemical pathways we perform several statistical enrichment tests. In addition to common enrichment tests, we established a method that takes network topology into account by applying adjusted wavelet transforms on an elaborated and 2D grid representation of curated pathway maps from the Kyoto Enzyclopedia of Genes and Genomes. Besides regulatory shifts common to most tumors like purine and pyrimidine biosynthesis as well as folate-mediated metabolism of the one carbon pool in respect to increased nucleotide production, we also detected tumor type specific regulatory shifts. Specifically for glioblastoma, we spotted branched chain amino acid metabolism and biochemical pathways involving glycans.