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.

• Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons
• Serum Creatine, Not Neurofilament Light, Is Elevated in CHCHD10-Linked Spinal Muscular Atrophy
• Threshold of heteroplasmic truncating MT-ATP6 mutation in reprogramming, Notch hyperactivation and motor neuron metabolism
• ITPR3 encoding IP3 receptor type 3 (IP3R3) is a disease gene for dominant Charcot-Marie-Tooth disease
• Mitochondrial intermembrane space proteins CHCHD2 or CHCHD10 impact respiration in human motor neurons
• Distinct effects on mRNA export factor GANP cause neuropathy plus phenotypes

We investigate the consequences of disturbed mitochondrial proteostasis on cell and tissue function, as well as the role of mitochondria in maintaining cellular proteostasis. In relation to human disease, we are particularly interested in mitochondrial aminoacyl-tRNA synthetases that are associated with multiple tissue-specific mitochondrial diseases.

• Proteotoxic stress responses to loss of GRPEL1, a co-chaperone of mitochondrial HSP70, in skeletal muscle
• Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure (preprint)
• Redox regulation of GRPEL2, a co-chaperone of mitochondrial HSP70
• Editing activity by mitochondrial alanyl-tRNA synthetase is essential in mammals