Heinrich Kovar Group

Heinrich Kovar Group

Heinrich Kovar
Email: heinrich.kovar(at)ccri.at

Molecular Biology of Solid Tumours

Our research focus is the study of Ewing Sarcoma, a highly malignant bone-tumor in children and adolescents.

Team

The Molecular Biology Group focuses predominantly on basic research with the aim of translating clinical observations into molecular patterns, and molecular patterns into diagnostic/prognostic tools and novel treatment options. For many years, our research has focused on Ewing sarcoma. There is an urgent need for new treatment options for this very malignant form of bone cancer in children and adolescents. Due to its relatively simple genetic makeup, this disease is particularly open to further research.

The search for the right medication.

The central genetic aberration of Ewing sarcoma is a fusion between the Ewing sarcoma gene EWS and the ETS oncogene FLI1 that results in the production of an aberrant gene regulatory protein, EWS-FLI1. Thus, the study of Ewing sarcoma also serves as a seminal example for ETS oncogene-driven oncogenesis in human cancer. The overall aim of our research is to identify druggable vulnerabilities in the molecular pathways that drive Ewing sarcoma pathogenesis. Since transcription factors - such as EWS-FLI1 – have thus far represented rather inaccessible therapeutic targets, we want to decode the molecules and biochemical pathways, which are active up- and downstream of EWS-FLI1 and are modulating EWS-FLI1 expression and its effects. We are approaching this goal through a multidisciplinary systems approach (European Framework 7 program funded project “ASSET”) using experimental perturbation in Ewing sarcoma cell lines, in-silico prediction and validation in primary tumour samples.

Studies of gene regulatory networks of the protein EWS-FLI1.

Our research focusses on the gene regulatory networks of EWS-FLI1. We use pangenomic screening approaches (mRNA, microRNA, transcription factor binding and epigenetic profiling by array technologies and high-throughput sequencing) to generate hypotheses about mechanisms of altered gene regulation in Ewing sarcoma. These are subsequently tested by targeted pathway perturbations using genetic (RNA interference, ectopic overexpression and targeted mutagenesis of genes of interest) and chemical (small molecule inhibitors) tools. We also investigate the influence of the microenvironment (e.g. hypoxia, immune cells) on the EWS-FLI1 gene regulatory network in vitro, and study characteristics associated with malignancy and metastasis formation in European (ERA-NET project PROVABES; FP7 project ASSET) and internationally funded (Liddy Shriver Sarcoma initiative) collaborative projects. Finally, we engage in Europe-wide clinical Ewing sarcoma trials (Euro Ewing 99, Ewing 2008; European Ewing Sarcoma Consortium) to prospectively test the potential prognostic utility of EWS-FLI1 and its downstream effectors in terms of the course of the disease and according treatments [1].

Team Molecular Biology of Solid Tumours

Univ.-Prof. Dr. Heinrich Kovar (PhD)

Univ.-Prof. Dr. Heinrich Kovar (PhD)

Group Leader

heinrich.kovar(at)ccri.at +43 1 40470 4092

Priv.-Doz. Dr. Dave Aryee (PhD)

Priv.-Doz. Dr. Dave Aryee (PhD)

Staff Scientist

dave.aryee(at)ccri.at +43 1 40470 4041 read more

Jozef Ban, PhD

Jozef Ban, PhD

Staff Scientist

jozef.ban(at)ccri.at +43 1 40470 4045

Branka Radic-Sarikas, PhD

Branka Radic-Sarikas, PhD

Postdoctoral Fellow

branka.radic-sarikas(at)ccri.at +43 1 40470 4045

Lisa Bierbaumer, MSc

Lisa Bierbaumer, MSc

PhD Student

lisa.bierbaumer(at)ccri.at +43 1 40470 4042

Rahil Noorizadeh, MSc

Rahil Noorizadeh, MSc

PhD Student

rahil.noorizadeh(at)ccri.at +43 1 40470 4034

Mathias Ilg, BSc

Mathias Ilg, BSc

Master Student

mathias.ilg(at)ccri.at +43 1 40470 4033

Ing. Karin Mühlbacher

Ing. Karin Mühlbacher

Technician

karin.muehlbacher(at)ccri.at +43 1 40470 4044

Dr. Eleni M. Tomazou (PhD)

Dr. Eleni M. Tomazou (PhD)

Collaborator

eleni.tomazou(at)ccri.at +43 1 40470 4045 read more