The role of epigenetic modifiers in liver cancer plasticity (B05)

• Subject Area: Pathology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314905040

Project B05 (Tschaharganeh; The role of epigenetic modifiers in liver cancer plasticity) aims to unravel the role of epigenetic modifiers, which are frequently altered/mutated in liver cancer in (lineage-dependent) tumor suppression and tumor cell plasticity. It could show that disruption of BAP1, an epigenetic modifier, promotes ICCA development but surprisingly prevents HCC development in respective model systems, a phenomenon termed lineage dependent tumor-suppressor lethality (LTL). This leads to the hypothesis that ICCA-promoting BAP-disruption can be repurposed as synthetic lethality in HCC. This hypothesis will be followed in the new funding period using specific mouse model systems combined with high-throughput screens by BAP1 disruption in different ICCA and HCC genotypes and correlating the findings with human tumor probes. The LTL phenomenon will be tested for other ICCA and HCC specific alterations of epigenetic modifiers by focussed CRISPR screens and in vivo validation. The project provides a completely new approach to the oncogenic role of epigenetic modification and its potential therapeutic use.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professor Dr. Darjus-Felix Tschaharganeh