In our research study we cover two main topics:
In the field stem cell based disease modeling:
- Engineering of patient-specific hiPSCs to precisely and efficiently correct or to introduce gene variants for streamline production of isogenic lines for disease modeling.
- Differentiation of engineered hiPSCs into patient-specific cells of interest and 3D brain organoids in combination with extensive phenotyping (single cell sequencing, mRNA isoforms analysis, shifts in splicing, CX7 Hight Content Screening) along the neuronal lineage to unravel diseased phenotypes.
- Mapping of differentially expressed genes into the functional pathways and networks reflecting pathological events for identification of novel modules as a possible therapeutic approaches.
- Conversion of engineered hiPSCs into cells of interest for high throughput drug and compounds screening.
In the field of technology development:
- Enhancing precise genome engineering for gene therapy by manipulation of DNA repair pathways combined with the inhibition of the key NHEJ regulators, upregulation of the HDR proteins and modifications of the repair templates.
- Identification of the main factors shifting DSB repairs towards HDR pathway.
- Further searching for alternatives of HDR for in vivo genome editing in non-dividing somatic cells to develop quality tools for effective and safe genome editing in human patients as somatic gene therapy.
- Development of strategies and tools to monitor and/or reduce Cas9 off target effect in human cells.