Systems Genetics and Gene Regulatory Networks
We use network-based approaches to study molecular consequences of inherited kidney disease risk variants. We integrate human genetic, epigenetic, transcriptomic and protein data to reconstruct causal gene regulatory networks. We then identify master regulators and key molecular drivers of such networks to better define novel targets for potential therapeutic interventions.
We use this approach to study immunologic endophenotypes related to glomerular diseases that are reflective of the complement activation, IgA1 production and IgA1 glycosylation. For example, defective O-glycosylation of IgA1 represents one of the key pathogenic features of IgA nephropathy and Henoch-Schönlein purpura nephritis; galactose-deficient IgA1 promotes the formation of pathogenic immune complexes and their glomerular deposition.
Using systems genetics approaches, we re-construct IgA1 interactomes (i.e. global maps of molecular interactions in human IgA1-secreting cells) to define the precise molecular events contributing to IgA1 glycosylation defects.