Laboratory for Metabolic Networks

We utilize screening technologies to identify genes and chemicals that are critical for linking mitochondria to complex disease pathways. We are exploring the role of mitochondria in the following disease areas.

 

 

Mitochondria in inflammation

We recently used our screening toolbox to identify chemicals that can activate and suppress an inflammatory pathway called NLRP3 inflammasome. We uncovered niclosamide (mitochondrial uncoupler) as a new activator of this pathway. By pursuing the mechanism of action of niclosamide, we learned how mitochondrial energy metabolism, in partnership with glycolysis, is linked to inflammasome activation.

 

We are also extending our screening approach to understand how other environmental toxins and particles activate inflammasome. We are continuing to explore how different key cellular processes, especially in regards to cellular metabolism, work together during inflammasome activation. 

 

Mitochondria in neuronal death

We have begun to study how mitochondrial stress leads to neuronal cell death in the context of Parkinson’s disease. In collaboration with our colleagues from the Luxembourg Centre for Systems Biomedicine (LCSB), we are using focused chemical screens and metabolomics to understand how metabolic pathways respond to mitochondrial stress. We hope to understand how mitochondrial perturbation triggers various stress response pathways and to search for ways to delay or avert neuronal cell death.