Kate Keller earned a BSc in Cell Biology from University of Glasgow, Scotland, UK. She then attended the University of Edinburgh, Scotland, where she received a PhD in Biochemistry in 1998. Having specialized in studies of molecules of the extracellular matrix, she continued her research interests as a post-doctoral fellow in the laboratories of Dr Nick Morris and Dr Lynn Sakai at the Shriners Hospitals for Children, Portland, OR. Subsequently, she joined the lab of Dr Ted Acott at the Casey Eye Institute as a research associate in 2003 and was promoted to research assistant professor in 2008. Summary of current researchPrimary open-angle glaucoma is frequently associated with elevated intraocular pressure (IOP), which is due to increased resistance to aqueous humor flow through a filter-like tissue in the front of the eye called the trabecular meshwork (TM). In our lab, we are interested in identifying the molecular components of the blockage (resistance) and how we can manipulate these components to enable greater aqueous humor flow through the TM. Cells of the TM synthesize and secrete proteins into the extracellular matrix. It is these extracellular matrix components that we believe comprise the resistance. When TM cells are subjected to sustained elevated IOP, they initiate remodeling of the extracellular matrix where some proteins are destroyed and others are synthesized as replacement molecules. This produces a new, reduced resistance to allow greater aqueous outflow through the TM thereby decreasing IOP. However, the pathways involved in this process are largely unknown. In my laboratory, we are investigating ADAMTS4, an enzyme that degrades certain extracellular matrix molecules and increases aqueous outflow, and glycosaminoglycans, which are components of the resistance. Identification of the molecules that initiate the remodeling process, their proteolytic targets and the modes and sites of action should allow us to understand how IOP is adjusted. This is critical in order for us to design new therapeutic interventions for glaucoma patients. The gene ASB10 was recently identified by Dr Mary Wirtz at the Casey Eye Institute to cause primary open angle glaucoma (POAG). ASB10 mRNA is expressed both in the TM and in the retina. However, its biological function remains unknown. In collaboration with the Wirtz laboratory, we aim to determine the molecular interactions of wild-type and mutant ASB10 protein in TM cells and to further delineate its role in IOP homeostasis.

Glaucoma Glaucoma pathophysiology, extracellular matrix