1. CDR proteins: Location, function and interaction

The pathological mechanisms underlying Paraneoplastic Cerebellar Degeneration (PCD) are largely unknown. It is believed that the expression of tumors and genetic alterations of the CDR proteins, especially CDR2L, may trigger an immune response targeting both cancer cells and Purkinje neurons that endogenously express the CDR proteins. However, the mechanisms of immune activation and neural injury induced by these intracellular neural proteins remain unknown. This is partly due to our limited understanding of the biological properties of the CDR proteins.

Our objective is to enhance the understanding of the functional role of CDR proteins, as well as the cellular and molecular mechanisms underlying the death of Purkinje neurons in PCD. Likely, alterations in ion channel functions in the plasma membrane and/or subcellular membranes are the initial key steps in neurological diseases. Growing evidence indicates that both CDR2 and CDR2L play crucial roles in regulating neuronal cell signaling.

To deepen our comprehension of the CDR proteins, we have developed ovarian cancer cell lines in which the CDR1, CDR2, and CDR2L genes have been knocked out using CRISPR/Cas9. Employing a multi-omics approach, we are assessing the effects of the knockout by integrating data from the cells' transcriptome, proteome, and secretome.

Click the links below for more information about our ex-vivo models and the proteins we are investigating.