Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases. It is caused mainly by mutations in PKD1 and PKD2, which encode polycystin 1 (PC1) and polycystin 2 (PC2), respectively.

Although the molecular mechanism of cystogenesis in PKD is still controversial, accumulating evidence in human genetics and hypomorphic rodent models suggests that the severity of the disease closely correlates with a decreasing dosage of functional polycystins. Proper targeting and maintenance of polycystins on the cilia surface are critical for cilia as mechanosensors.

Theoretically, restoring the functional level of ciliary polycystins is a promising therapeutic strategy to delay or even prevent cystogenesis. However, exploration of this strategy is impeded by a lack of knowledge of how the ciliary targeting and maintenance of polycystins are controlled. Dr. Hu's team focuses on understanding the ciliary trafficking of polycystins and identification of druggable targets to be used in PKD therapeutics.