SBI – Department of Systems Biology and Bioinformatics
Faculty of Computer Science and Electrical Engineering
University of Rostock
Ulmenstrasse 69 | 18057 Rostock
Germany
+49 381 498-7571
olaf.wolkenhauer@uni-rostock.de
Research interest
Bioinformatic analysis in the field of radiation biodosimetry
"I am interested in analyzing radiation-induced changes in transcriptional responses and in biomarker discovery for radiation dose prediction."
Protection of humans from the adverse effects of ionizing radiation is a major goal of radiation biodosimetry. In the case of accidental exposures to radiation the development of effective counter measures requires information on the actual exposure dose. Gene expression analysis is a promising approach to predict the radiation dose in a fast and accurate manner.
The questions we focused on is: What are the transcriptional changes in consequence of ionizing radiation and is it possible to accurately predict the radiation dose of irradiated blood based on transcriptome analysis?
Ionizing radiation is known to function as a carcinogen, but also plays a major role in cancer therapeutics in the field of radiation therapy. On the transcriptional level ionizing radiation initiates a complex series of expression alterations, which are dependent upon genetic background, dose, dose-rate, and time after irradiation. A better understanding of individual radiation-induced cellular processes may help us to develop optimized therapy protocols or to stem long-term effects of ionizing radiation.
We identified genes showing a radiation-induced and dose-dependent expression status, most of them functionally linked to radiation related biological processes (i.e. apoptosis, DNA-damage or cell-cycle regulation). Furthermore, we established p-value and fold-change-driven prediction framework to extract small gene expression signatures which are particularly suitable for dose estimation.
The genes identified are potential robust biomarkers, which are particularly suitable for dose level discrimination at a window of time that would be appropriate for life-saving medical triage.
Academic background
| 2007 - 2014 | Doctorate Degree in Computer Science University of Rostock, Rostock/Germany |
| 2000 - 2007 | Masters Degree in Bioinformatics (Dipl. Bioinformatiker) University of T |
Selected publications
Gene expression in low and high dose-irradiated human peripheral blood lymphocytes: Possible applications for biodosimetry
Radiation Research 178:304-312
A Frequency Based Gene Selection Method to Identify Robust Biomarkers for Radiation Dose Prediction
International Journal of Radiation Biology 3:267-276
The multikinase inhibitor Sorafenib displays significant antiproliferative effects and induces apoptosis via caspase 3, 7 and PARP in B- and T-lymphoblastic cells
BMC Cancer 10: 560
Network-Assisted Disease Classification and Biomarker Discovery
In Springer (2016), Systems Medicine, pp 353-374
ISBN 13 (print): 9781493932825
ISBN 13 (online): 9781493932832
URL: http://link.springer.com/protocol/10.1007/978-1-4939-3283-2_16
Reverse Engineering of Biological Networks
in: Methods in Bioengineering: Systems Analysis of Biological Networks; Jayaraman A, Hahn J (eds.); Artech House 2009.
ISBN 13 (print): 9781596934061
Identification of gene-based biosignatures for radiation biodosimetry
58. Biometrisches Kolloquium, Berlin, Germany, March 2012
Venue: Berlin, Germany
Identification of radiation-specific gene expression changes in human PBL after ex vivo irradiation suitable for biodosimetric applications
14th International Congress of Radiation Research, Warsaw, Poland, August 2011
Venue: Warsaw, Poland
Gene expression analysis in Jurkat cells after exposure to I-123-iododeoxyuridine, Gamma-rays and Alpha-particles
14th International Congress of Radiation Research, Warsaw, Poland, August 2011
Venue: Warsaw, Poland
A p-value and fold-change driven gene selection method for radiation dose prediction
EPRBioDose, Mandelieu-La-Napoule, France, October 2010
Venue: Mandelieu-La-Napoule, France
Gene expression pattern analysis in human PBLs as a tool for radiation biodosimetry
EPRBioDose, Mandelieu-La-Napoule, France, October 2010
Venue: Mandelieu-La-Napoule, France
Radiation responsive genes in human lymphocytes as a tool for radiation biodosimetry
GBS Tagung, Hamburg, Germany, September 2010
Venue: Hamburg, Germany
A Data Analysis Workflow for the Identification of Expression Signatures Functioning as Molecular Biodosimeters
German Conference of Bioinformatics, Halle (Saale), Germany, September 2009
Venue: Halle (Saale), Germany
Gene Expression pattern analysis as a tool for radiation biodosimetry
ERRS, Prague, Czech Republic, August 2009
Venue: Prague, Czech Republic
Detecting Differential Gene Expression in ALL Cell Lines Treated with the Multikinase Inhibitor Sorafenib
Systems Biology for Medical Applications, Summer School, Costa Adeje, Soain, 30 October 2008
Venue: Costa Adeje, Soain
Sorafenib inhibits proliferation in B- and T- Lymphoblastic cell lines via the PI3k/AKT Pathway
Ash, San Francisco, USA, 2008
Venue: San Francisco, USA
Transcriptional Responses to Radiation Exposure Facilitate the Discovery of Biomarkers Functioning as Radiation Biodosimeters
The development of new methods for a retrospective quantification of the radiation dose of exposed individuals is of widespread interest. To this end, I developed a computational framework for biomarker discovery and radiation dose prediction and successfully identified gene signatures with which low and medium to high radiation doses can be accurately quantified. To enhance our understanding of the radiation-induced transcriptional response, I additionally analyzed microarray data of human PBLs after ex vivo gamma-irradiation and characterized affected functional processes and pathways.
Defense: 13 May 2014