Group leader: Lajos Mátés

Email: mates.lajos@brc.hu

Group website:

Group members

Name

Title

 

 

Lajos MÁTÉS

senior research associate

publications

CV

Andrea MÁTÉS-NAGY

research associate

publications

CV

Gergely IMRE

scientific-technical adminstrator

 

 

Andrea BAKNÉ DRUBI

junior research associate

 

 

Réka KARKAS

Ph.D. student

 

 

Abdullah KHALDOON

Ph.D. student

 

 

Raya MAY

Ph.D. student    

Research                                  

The role of LINE1 retrotransposons in carcinogenesis

To our knowledge, LINE1 retrotransposons are the only currently active mobile genetic elements in the human genome, where their number has now exceeded 450,000 copies. Most of them have already been inactivated, but the number of intact, retrotransposition competent elements is still around 100. The low level of LINE1 activity has previously been known in human gametes and was thought for a long time to be the only point in the human body where this phenomenon can be detected. As a result, a new germ cell-derived LINE1 retrotransposon integration is present in approximately every 200th children. Only a small fraction of these events cause disease, but to date, a large number of such inherited diseases induced by LINE1 integration have been described. This includes, for example, some cases of haemophilias. There are several defensive biological processes in the human body that tightly control LINE1 retrotransposition outside of gametes (microRNAs, endo siRNAs, DNA methylation, APOBEC proteins, etc.). By now, however, it has become clear that under pathological conditions, the functioning of these systems can be impaired, thus paving the way for LINE1 activity anywhere in our body. New LINE1 integrations resulting from LINE1 retrotransposition may create cancer driver mutations, thus aiding tumor evolution. In line with this, recently a number of driver mutations resulting from new LINE1 integration have been described in a variety of tumors.

Our research group investigates the regulation of the activity of LINE1 elements and their role in carcinogenesis in mammalian cell culture and transgenic mouse model systems using genetic, molecular, biochemical and bioinformatics approaches.

 

Molecular analysis of DNA transposons as gene delivery vehicles for gene therapy

Gene therapy procedures hold great promise for a number of serious diseases for which effective, conventional therapy is not available. During gene therapy, only the cells of the organ or tissue affected by the disease are genetically modified. In classical gene therapy interventions, a functional copy of the disease-causing mutant gene is introduced into these cells. Making interventions safer with randomly integrating vectors that result in highly efficient therapeutic gene delivery is essential for their routine clinical use. One promising branch of research in this regard is the application of DNA transposons. A number of gene therapy procedures based on the use of Sleeping Beauty and piggyBac DNA transposons are currently undergoing clinical trials worldwide.

Our research group is working on the characterization of therapeutic gene delivery mediated by Sleeping Beauty and piggyBac DNA transposons in a transgenic mouse model of human disease using genetic, molecular, biochemical and bioinformatics approaches.