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Project 4: The Fasciola kinome as a source for drug development

From Cancer Research to Parasite Control

Protein kinases regulate a multitude of cellular processes and present promising targets for drugs, not only for combating cancer but also against multicellular infectious agents. Both cancer and parasites like worms have in common that stem cells play a crucial role in their growth. Our hypothesis is that the inhibition of selected protein kinases can be used as a therapeutic approach against the liver fluke Fasciola hepatica, a globally prevalent parasite causing zoonotic disease and neglected tropical disease (NTD) in humans.

 

Kinases in the Liver Fluke: An Unexplored Territory

Protein kinases in liver flukes have been scarcely studied thus far. We aim to change that. Within the scope of our DRUID-funded project, we will (1) bioinformatically identify and genetically validate potential drug targets in the Fasciola kinome, (2) identify kinase inhibitors active against the liver fluke, and (3) characterize the mode of action of kinase inhibitors using biochemical and imaging techniques.

In collaboration with the Spengler research group, the application of AP-MALDI mass spectrometry imaging for "Drug Imaging" in parasite tissues has been established. This enables us to investigate the uptake route, kinetics, and tissue tropism of kinase inhibitors in liver flukes (Houhou et al. 2019, Morawietz et al. 2020).

 

 

 

 

 

 

 

                                                                                        Strategy for the identification of protein kinase inhibitors

                                                                                        as drug candidates against the liver fluke Fasciola hepatica

 

 

 

Own publications on this topic

 

Houhou H, Puckelwaldt O, Strube C, Haeberlein S. Reference gene analysis and its use for kinase expression profiling in Fasciola hepatica. Sci Rep (2019) 9:15867

Morawietz CM, Houhou H, Puckelwaldt O, Hehr L, Dreisbach D, Mokosch A, Roeb E, Roderfeld M, Spengler B*, Haeberlein S*. Targeting kinases in Fasciola hepatica: