From genes to mechanisms
We investigate mitochondrial dynamics and glial lipid metabolism in neurological disease.
CDK19 and Mitochondrial Dynamics
Collaborative studies show that cytoplasmic Cdk8/CDK19 promotes mitochondrial fission through Drp1 phosphorylation. Increasing expression of fly Cdk8 or human CDK19 improved defects in pink1-deficient flies, linking mitochondrial regulation to a model of inherited Parkinson’s disease.
Lipid Metabolism and Neurological Disease
Excess very-long-chain fatty acids increase glial sphingosine-1-phosphate (S1P) production, triggering neuroinflammation. Reducing fatty acid accumulation and S1P signaling improved disease-related phenotypes in flies and a mouse model of multiple sclerosis.
The ACOX1 gain-of-function variant linked to Mitchell syndrome increases reactive oxygen species and damages glia. N-acetylcysteine amide (NACA) suppressed variant-related defects in preclinical experiments.
Collaborative studies in patient cells and Drosophila link ASAH2 deficiency to disrupted sphingolipid balance and progressive neurological symptoms.
Selected publications (3)
- Chung HL, et al. Very-long-chain fatty acids induce glial-derived sphingosine-1-phosphate synthesis, secretion, and neuroinflammation. Cell Metabolism. 2023;35(5):855–874.e5.
- Chung HL, et al. Loss- or Gain-of-Function Mutations in ACOX1 Cause Axonal Loss via Different Mechanisms. Neuron. 2020;106(4):589–606.e6.
- Scala M, et al. ASAH2 deficiency affects sphingolipid homeostasis and neuromotor control, causing a progressive neurological disorder. HGG Advances. 2026;7(2):100587.
Drosophila Core
Functional genomics & collaboration
The Drosophila Functional Genomics Core supports collaborative human variant studies and custom fly experiments.