Research

Identification of pathogenic sequence variants

Up to date disease causing mutations have been identified in eleven genes of the GPI-anchor synthesis pathway. However, currently in about half of the suspected cases of GPI-anchor deficiencies no causal mutation is detected. We apply next-generation sequencing methods and statistical analysis tools to identify further, yet unknown genes that play a role in the GPI-anchor synthesis pathway. The bioinformatics algorithms that we develop as well as the sequence variants that we detect in our research studies are made available on  Öffnet externen Link im aktuellen FensterGeneTalk.

Characterisation of GPI-anchor deficiencies

For hundreds of proteins we know that they are GPI-anchored (GPI-AP). However, only for a few of these GPI-APs, such as CD59, CD55 and alkaline phosphatase, the effect on expression and function of a defect in the GPI-anchor synthesis has been analysed. The antibody eculizumab shows exemplarily how important it is to know the consequences of a GPI-anchor synthesis defect on specific GPI-APs for developing therapies: Patients that develop PNH because of a null mutation in PIGA, benefit from the complement system inhibitor eculizumab that compensates effectively the reduced surface levels of the membrane attack inhibitor proteins CD59 and CD55.

We use flow cytometry and proteomics to screen for the effects of a multitude of pathogenic mutations. By this means we would like to identify the GPI-APs that are impaired in each cell type, especially neurons, and that might play a role in the pathophysiology.

We also examine mouse models with tissue specific GPI-anchor deficiencies to learn more about the development of the neurologic abnormalities the affected individuals are showing. We hope to gain a deeper understanding of biology of GPI-anchor deficiencies and also to pave the ground for the development of new treatments.

Publications

You can find scientific papers of our group Opens external link in current windowhere.

Partners

There are several other groups working on GPI-anchor deficiencies. More information about inherited GPI deficiencies, IGDs, can also be found on the website of Yoshiko Murakami and Taroh Kinoshita.

Research database

For more details please use the Charité undefinedresearch database.