Skip to main content

Cancer Gene Discovery Using Somatic Gene Transfer in Mice

Final Report Summary - CGDM (Cancer Gene Discovery Using Somatic Gene Transfer in Mice)

After a long research period spent abroad, the PI started to build his independent research group in 2011; the Laboratory of Cancer Genome Research ( at the Institute of Genetics, Biological Research Centre (BRC), Szeged, Hungary. In the BRC he launched independent research on the examination of the genetic drivers of cancer development.
The main research objective of the new laboratory, that was planned to be accomplished by the support of the MC-CIG grant, the creation of a somatic gene transfer system in the mouse liver, has substantially been achieved. The laboratory successfully created a highly efficient transgenic cell replacement system in mice, allowing to build transgenic liver models composed of >95% transgenic hepatocytes. To reach this goal the research group harnessed the mouse model of human tyrosinemia type I, a fatal disease with progressive liver dysfunction, and the transposon-based chromosomal delivery of the therapeutic gene for either ex vivo or in vivo genetic correction of the diseased primary hepatocytes. The successful correction of the diseased cells induced an intensive liver regeneration, finally resulting in a complete replacement of diseased cells with corrected ones. Importantly, this cell replacement system also allows the efficient co-introduction of any arbitrary transgene of interest together with the therapeutic gene, into the genome of the liver repopulating hepatocytes. Coupling of the therapeutic gene with transgenes modeling cancer driver mutations enables the PIs laboratory to test the in vivo effect of harmful somatic mutations potentially initiating cancer, a disease dependent on the accumulation of somatic genetic events.
Due to the fact that the established somatic gene transfer system is utilizing transposon-based ex vivo or in vivo gene therapeutic protocols, the laboratory is also investigating and developing further such gene therapeutic protocols.
By the help of the MC-CIG grant the PI could successfully establish his independent research group and demonstrate a good scientific progress to be awarded with a permanent position in the Institute of Genetics, BRC, Szeged, Hungary.