Disentangling tumor specific regulatory mechanisms of prothrombin gene expression by differential high-content screening in an integrated genetic reporter system

• Applicant: Dr.-Ing. Essak Khan, Ph.D.
• Subject Area: Hematology, Oncology ; Pathology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 507581264

Thrombin is the central protease involved in blood coagulation. Beyond its well-established role in stemming blood loss and function in thrombosis, it is involved in (patho)physiological conditions like sepsis and various cancers. Prothrombin, the precursor of thrombin is primarily synthesized in the liver, but in case of cancer, it is also extra-hepatically synthesized in tumors and promotes tumor progression (in mice and human). The underlying regulatory mechanisms governing tumorigenic prothrombin expression are poorly understood. By using an innovative genetic reporter tool, I now want to identify the underlying mechanisms governing (ectopic) prothrombin expression in tumors. To this end, we intend to establish a methodology using high content screening in vivo and in vitro to identify regulatory pathways and potentially new therapeutic avenues to interfere with detrimental prothrombin expression in a tissue-specific manner. The animal experiments will be complemented by counter validation of the obtained findings in human tumor specimens to obtain first insights into the translational prospects.

• DFG Programme: Research Grants