Our Research: An Overview
Our laboratory interests focus on the role inositol signaling plays in development and disease. Our specific interests are in eye diseases, specifically cataract and glaucoma development and retinal degeneration. However, our findings are generally applicable in many other cell types.
Eye disease in mouse models
Zebrafish modeling
Research by Study Area
Lowe Syndrome
We have found evidence of an important regulator of vesicular trafficking in the eye that may control IOP. Oculocerebrorenal syndrome of Lowe (Lowe syndrome) is a rare X-linked recessive disorder caused by a mutation in the OCRL1 gene, which encodes an inositol polyphosphate 5-phosphatase that controls the levels of phosphoinositides, which in turn are important in vesicular trafficking and cilia regulation. In addition to brain and kidney defects, Lowe patients exhibit cataracts and frequently develop elevated IOP and congenital glaucoma. OCRL is localized inthe primary cilia, and PI(4,5)P2 is increased in cells derived from patients with Lowe syndrome and in OCRL deficient cells, suggesting that OCRL plays a critical role in ciliary phosphoinositide regulation.
Joubert Syndrome
INPP5E in zebrafish development and primary cilia function
The second arm of our research interest is in the role of inositol signaling in the formation of primary cilia in retinitis pigmentosa (RP). RP is a group of diseases marked by photoreceptor degeneration and progressive vision impairment. Patients with Joubert syndrome develop retinitis pigmentosa, polydactyly, mental retardation and renal cysts. Mutations in INPP5E, another inositol polyphosphate 5-phosphatase, have been identified in Joubert patients. Previously, INPP5E knockout mice demonstrate primary cilia defect as well as organogenesis defect including anophthalmia.
Aqueous Humor Outflow in the Eye
We are interested in vesicular trafficking in cellular functions, which underlies many different diseases including developmental and degenerative ocular conditions. We hope to make advances in the basic understanding of cell biology of the primary cilia by examining the inositol phosphate metabolism and effects on intraocular pressure regulation. Primary cilia is found in the trabecular meshwork, a sponge-like structure in the anterior chamber of the eye where aqueous flows out as the it's being produced by the ciliary body. Disruption in phosphotases found in primary cilia have produced increased IOP and reduction in aqueous outflow facility. The exact regularoty role of primary cilia is being investigated.
