My research group is primarily interested in defining molecular events associated with tubule formation. To identify proteins important in this process we study inherited disorders that result in abnormal tubule formation/maintenance in the kidney. These polycystic kidney diseases (PKD) are a group of disorders that cause cyst development in the kidney (and often elsewhere), ultimately resulting in renal failure. We have used genetic (positional cloning) approaches to identify genes causing the two major forms of PKD: autosomal dominant (ADPKD) and autosomal recessive (ARPKD), plus a syndromic form of the disease, Meckel syndrome (MKS). ADPKD is a common (frequency of 1/400-1000), late-onset disorder that accounts for ~5% of patients requiring kidney transplant or dialysis at an annual cost of >$1 billion in the US. ARPKD is usually an infantile disease that is associated with a high level of neonatal death and childhood renal failure. MKS is a lethal, recessive disease that also involves central nervous system abnormalities. In the past few years a link between various forms of PKD and primary cilia, a sensory organelle that protrudes from the apical surface of epithelial cells, has become clear. The ADPKD proteins may be involved in detecting fluid flow within tubules, using cilia, while those associated with ARPKD and MKS may have pivotal roles in developing and maintaining functional cilia.
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