Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common genetic disease in humans. It is inherited as a dominant trait and caused by a single gene, affecting 500,000 people in the United States and 6 million worldwide. Autosomal Recessive Polycystic Kidney disease (ARPKD) is often lethal at birth and is a common cause of renal failure in children. Research into the molecular genetics, cell biology, and pathophysiology of these diseases has led to new insights into their underlying mechanisms and studies are in progress to translate this information to the development of new small molecule inhibitor and gene therapies.

Current areas of PKD research in the Division of Nephrology include:

1. Examination of the role of phosphorylation, de-phosphorylation, and protein-protein interactions of the polycystin disease proteins with regard to normal and abnormal function.
2. Evaluation of polycystin function in regulating interactions with the extracellular environment via cell-matrix focal adhesions.
3. Analysis of cell-cell adherens junctions and apical membrane primary cilia by determination of binding partners, complex formation, and downstream signaling leading to adhesion, migration, tubulogenesis, and renal morphogenesis.
4. Development and use of cell based adhesion and migration assays to examine the effects of potential drug therapies based on abnormal receptor and downstream signaling pathways identified in ADPKD and ARPKD cells.
5. Development of gene therapy approaches in human renal epithelia cell and mouse kidney organ culture systems utilizing adeno-associated virus constructs to restore function by replacing or repairing the function of the defective PKD1 gene.
6. Translational/Clinical development of a PKD clinical clinic and genetic database.

HFCT Lateral PC1

PC1 Gamma ADPKD