Research interests
Rethinking antiviral drug discovery
Ribosome dysfunction in neurodegeneration
Rethinking antiviral drug discovery
Most antiviral drugs target viral enzymes e.g. polymerases and proteases. This presents challenges, including narrow spectrum of activity and rapid acquisition of resistance.
An alternative approach is to target host components that are both essential for the viral life cycle and dispensable for short-term cellular function.
Our work aims to discover and characterize host targeted strategies for broad-spectrum, low-resistance antiviral interventions.
Tools to explore ribosome function
Ribosome dysfunction in neurodegeneration
Rethinking antiviral drug discovery
Recent technological developments have revolutionized our understanding of ribosome function and regulation.
Our work expands the available toolkit for monitoring ribosome function by developing methods e.g. PUNCH-P to monitor nascent chain dynamics by mass-spectrometry, and viral reporters to monitor ribosome pausing and collisions.
We are currently adapting these to study translation errors and organism-specific differences in viral infection.
Ribosome dysfunction in neurodegeneration
Ribosome dysfunction in neurodegeneration
Ribosome dysfunction in neurodegeneration
Translation dysfunction is implicated in many types of human disease.
By analyzing ribosomes from cellular and mouse models of Huntington’s Disease (HD), we found that neurotoxicity is associated with sequestration of a key component that regulates ribosome function. This leads to ribosome collisions and increased susceptibility to stress, resulting in cell death.
Based on this new understanding, we seek to determine whether manipulating translation can delay cell death in HD.