HomeResearchIntramural ResearchResearch Branches at NHGRIGenetic Disease Branch Suchy Lab

Sharon F. Suchy, Ph.D. Associate Investigator Genetic Disease Research Branch B.S. College of William and Mary, 1978 Ph.D. Medical College of Virginia, 1984 (301) 402-2119 (301) 402-2170 suchy@nhgri.nih.gov Building 49, Room 4A66 49 Convent Drive MSC 4472 Bethesda, MD 20892-4472 Selected Publications Lowe Syndrome Mutation Database

We study the oculocerebrorenal syndrome of Lowe (OCRL), a rare X-linked disorder that is characterized by congenital cataracts, renal failure and mental retardation. Our laboratory demonstrated that OCRL is caused by the deficiency of the enzyme ocrl1, a phosphatidylinositol bisphosphate (PIP2) 5-phosphatase. This phospholipid molecule is localized to the Golgi apparatus, but exists in small quantities in all tissues, and plays a role in protein trafficking, the polymerization of the actin cytoskeleton, and second messenger signaling (it can form several second messenger molecules, including inositol 1,4,5-trisphosphate, diacylglycerol and phosphatidylinositol 3,4,5 trisphosphate, and is believed to be a second messenger itself). We are working to determine the mechanism by which ocrl1 causes the Lowe syndrome phenotype.

Our current efforts center on three questions: why a defect in the ocrl1 enzyme, which has a part in several major cell processes, leads to abnormalities only in specific tissues in Lowe syndrome patients (the lens, kidneys and brain); what role ocrl1 and other PIP2 5-phosphatases play in normal cell metabolism; and whether, or which of, these enzymes functionally overlap in particular tissues. We generated knock-out mice missing the ocrl1 gene and/or a related PIP2 phosphatase, and we are using tissues and cell lines from these mice and patient cell lines to investigate the function and interrelationship of these enzymes. In addition, we established novel enzyme assays that for the first time allow the measurement of different PIP2 phosphatases in particular tissues. We are using these assays to understand the specific role of PIP2 phosphatases.

Our OCRL research has had a positive impact on patients and their families. Most patients with this syndrome have unique deletion, missense or nonsense mutations. Consequently, the direct detection of mutations is not practical to confirm the clinical diagnosis. Our lab demonstrated it is possible to diagnosis OCRL by measuring PIP2 5-phosphatase activity in fibroblasts, and this assay is now the standard diagnostic test for this disorder.

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Last Updated: June 2004