Isbrandt, Dirk | Tsortouktzidis, Despina - C 08

Developmental and epileptic encephalopathy caused by HCN1 variants (HCN1-DEE) is a severe neurological disorder with drug-resistant seizures, developmental delay, and major comorbidities. Leveraging two established patient-derived mouse models, we seek to develop precision medicine approaches to HCN1-DEEs through comprehensive pathophysiological characterization and therapeutic development. We will conduct a multi-modal analysis combining electrophysiology and structural imaging to investigate how pathogenic HCN1-DEE variants affect neuronal excitability, circuit function, and development. Our key objectives include characterizing disease mechanisms across multiple scales and disease models—from molecular to behavioral—and identifying biomarkers for treatment monitoring and for targeting seizures and comorbidities to improve patient outcomes.

• Conditional mouse genetics and CRISPR inhibition strategies
• High-density in vivo electrophysiology
• Behavioral testing
• Transcriptomics

• Merseburg A, Kasemir J, Buss EW, Leroy F, Bock T, Porro A, Barnett A, Tröder SE, Engeland B, Stockebrand M, Moroni A, Siegelbaum SA, Isbrandt D, Santoro B. 2022. Seizures, behavioral deficits, and adverse drug responses in two new genetic mouse models of HCN1 epileptic encephalopathy. eLife 11. doi:10.7554/eLife.70826

For information about Prof. Isbrandt's research and work, please visit the following page: Isbrandt Lab

• Center for Molecular Medicine Cologne (CMMC)
• CRC 1451

• Center for Molecular Medicine Cologne (CMMC)