The focus of my research is to delineate the mechanism by which kidney disease risk variants in APOL1 accelerate the progression of kidney disease in humans. We found that induced expression of APOL1 kidney disease variants in cell culture is associated with increased loss of cellular potassium and dysregulation of signaling pathways known to cause kidney failure. The ultimate goal of my research is to extend these findings and translate them into improved diagnostic and treatment approaches to chronic kidney disease.

Using APOL1 transgenic cell lines, transgenic APOL1 mice and specific chemical inhibitors, we aim to fully characterize the effects of APOL1 risk variants on normal cellular signaling pathways. These robust systems will enable us to answer the question of how APOL1 risk variants result in cell death, and what protective mechanisms shield certain cells from APOL1 toxicity.

As an initial step towards translating our findings to human kidney disease, we collaborate with nephrologists and pathologists nationwide who provide us with kidney biopsy samples from individuals with APOL1 nephropathy. These biopsy samples provide us with a platform for validating relevant signaling pathways discovered in cell culture and transgenic mice.