To identify genetic causes of neurological diseases, we utilize genome-wide next-generation sequencing approaches. We investigate the molecular mechanisms of disease mutations by generating patient-specific motor neurons from reprogrammed skin fibroblasts. We use CRISPR/Cas9 genome editing in human induced pluripotent stem cells to generate disease models and isogenic controls. Currently, we have iPSC-projects on Charcot-Marie-Tooth disease type 1J (ITPR3 gene), spinal muscular atrophy Jokela type (SMAJ, CHCHD10 gene), peripheral neuropathy caused by MT-ATP6 defects, and mitochondrial aminoacyl-tRNA synthetase diseases (AARS, DARS2, SARS2). In addition, we investigate the mechanisms of how metabolism regulates motor neuron differentiation.
Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy
Editing activity by mitochondrial alanyl-tRNA synthetase is essential in mammals
We investigate the consequences of disturbed mitochondrial proteostasis on cell and tissue function, as well as the role of mitochondria in maintaining cellular proteostasis. Recently, we have been specifically interested in the nucleotide exchange factors GRPEL1 and GRPEL2 that regulate the protein folding cycle of the mitochondrial chaperone HSP70 in protein import into mitochondrial matrix.
Redox regulation of GRPEL2, a co-chaperone of mitochondrial HSP70