Bioinformatic Data Analysts
Maximilian Kauer, PhD, email: maximilian.kauer(at)ccri.at
Gerda Modarres, MSc, email: gerda.modarres(at)ccri.at
Niko Popitsch, PhD, DI, email: niko.popitsch(at)ccri.at
Maximilian Kauer, PhD
The Bioinformatics Unit works at the interface of molecular biology and bioinformatics. The BU supports CCRI researchers with the analysis, integration and interpretation of large scale genomics data. Custom analyses of array or sequencing based platforms are provided. Primary data analyses are performed by the application of state-of-the art tools. Established connections with bioinformatic collaborators facilitate access to the newest technologies. Integration of data from the CCRI with public sources is another key aspect of bioinformatic service provided by the BU. Custom databases making these integrated data sets available to the biologists are provided.
Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells: In a comparative study gene expression profiling data from primary LHC samples, plasmacytoid and myeloid dentritic cells, as well as from epidermal Langerhans cells were analysed. The pattern of RNA expression was used to address the question whether LCH form a distinct entity among these reference samples.
The leukaemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression: Gene expression profiling data for a knockdown of ETV/RUNX1 in ALL cell lines and transcriptomic data from primary ALL were integrated with databases of molecular pathways. As a result E/R repressed genes were found to be enriched in specific molecular functions whereas E/R activated genes did not show such a specific enrichment.
A molecular function map of Ewing’s Sarcoma: Gene expression profiling data from Ewing’s Sarcoma cell lines and primary ESFT tumours were intersected with gene expression data from normal tissues and databases of gene function. As a result mesenchymal stem cells (MSC) could be confirmed as the most likely tissue of origin of this aggressive bone-tumour. Furthermore a comprehensive map of molecular functions deregulated in Ewing’s Sarcoma was established.
Mechanisms of EWS-FLI1 mediated gene activation and repression: EWS-FLI1 is an aberrant regulator of gene expression and the key event in Ewing’s Sarcoma oncogenesis. Time resolved gene expression profiling data following a knockdown of EWS-FLI1 was integrated with transcription factor motif analysis and with ChIP-seq profiling of EWS-FLI1 and putative cooperating factors. As a result distinct gene regulatory modules could be identified that mediate gene activation and repression by EWS-FLI1.
The "miRegulatory landscape" of key players in Ewing’s Sarcoma: Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) combined with deep sequencing was used to comprehensively map sites of interaction between mRNAs and micro-RNAs (miRs). These data are being combined with miR and mRNA expression profiling in Ewing’s Sarcoma cell lines and primary tumours. For a set of genes that have been identified to have central roles in Ewing’s Sarcoma oncogenesis the hypotheses generated from the intersection of these genomic sources are being validated in detail.
Bilke S, Schwentner R, Yang F, Kauer M, Jug G, Walker RL, Davis S, Zhu YJ, Pineda M, Meltzer PS, Kovar H. (2013) Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and prostate cancer. Genome Res. 23(11):1797-809
Hutter C, Kauer M, Simonitsch-Klupp I, Jug G, Leitner J, Bock P, Steinberger P, Bauer W, Carlesso N, Minkov M, Gadner H, Stingl G, Kovar H, Kriehuber E. (2012) Notch is active in Langerhans Cell Histiocytosis and confers pathognomonic features on dendritic cells. Blood. 120(26):5199-208
Fuka G, Kauer M, Kofler R, Haas OA, Panzer-Grümayer R. (2011) The leukemia-specific fusion gene ETV6/RUNX1 perturbs distinct key biological functions primarily by gene repression. PLoS One. 2011;6(10):e26348.
Ban J, Jug G, Mestdagh P, Schwentner R, Kauer M, Aryee DN, Schaefer KL, Nakatani F, Scotlandi K, Reiter M, Strunk D, Speleman F, Vandesompele J, Kovar H. (2011) hsa-mir-145 is the top EWS-FLI1-repressed microRNA involved in a positive feedback loop in Ewing's sarcoma. Oncogene. 2011 May 5;30(18):2173-80. doi: 10.1038/onc.2010.581
Kauer M, Ban J, Kofler R, Walker B, Davis S, Meltzer P, Kovar H. (2009) A molecular function map of Ewing's sarcoma. PLOS ONE 4: E5415