Photo of Kate E Keller, Ph.D.

Kate E Keller Ph.D.

    • Associate Professor of Ophthalmology School of Medicine

BackgroundIn 1994, 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.

Education

  • B.S., University of Glasgow, Glasgow 1994
  • Ph.D., University of Edinburgh, Edinburgh 1998

Memberships and associations

  • Association for Research in Vision and Ophthalmology: 2003 - Present

Publications

  • "Mapping molecular differences and extracellular matrix gene expression in segmental outflow pathways of the human ocular trabecular meshwork" PLoS One March 31 2015
  • "Stem cells in the trabecular meshwork" Experimental Eye Research April 30 2009
  • "Specialized podosome-or invadopodia-like structures (PILS) for focal trabecular meshwork extracellular matrix turnover" Investigative Ophthalmology and Visual Science  2008
  • "Extracellular matrix turnover and outflow resistance" Experimental Eye Research April 30 2009
  • "Elastic modulus determination of normal and glaucomatous human trabecular meshwork" Investigative Ophthalmology and Visual Science April 2011
  • "Interleukin-20 receptor expression in the trabecular meshwork and its implication in glaucoma" Journal of Ocular Pharmacology and Therapeutics March 1 2014
  • "Ankyrin repeat and suppressor of cytokine signaling box containing protein-10 is associated with ubiquitin-mediated degradation pathways in trabecular meshwork cells" Molecular Vision July 25 2013
  • "Effects of modifiers of glycosaminoglycan biosynthesis on outflow facility in perfusion culture" Investigative Ophthalmology and Visual Science June 2008
  • "The effects of tenascin C knockdown on trabecular meshwork outflow resistance" Investigative Ophthalmology and Visual Science  2013
  • "Variants in ASB10 are associated with open-angle glaucoma" Human Molecular Genetics March 2012
  • "Intraocular pressure homeostasis" Journal of Ocular Pharmacology and Therapeutics March 1 2014
  • "Differential effects of caveolin-1 and -2 knockdown on aqueous outflow and altered extracellular matrix turnover in caveolin-silenced trabecular meshwork cells" Investigative Ophthalmology and Visual Science  2014
  • "Hyaluronan cable formation by ocular trabecular meshwork cells" Experimental Eye Research  2015
  • "Differential effects of ADAMTS-1, -4, and -5 in the trabecular meshwork" Investigative Ophthalmology and Visual Science December 2009
  • "Extracellular matrix gene alternative splicing by trabecular meshwork cells in response to mechanical stretching" Investigative Ophthalmology and Visual Science March 2007
  • "Perturbation of hyaluronan synthesis in the trabecular meshwork and the effects on outflow facility" Investigative Ophthalmology and Visual Science July 2012
  • "Extracellular matrix in the trabecular meshwork" Experimental Eye Research April 1 2015
  • "Segmental versican expression in the trabecular meshwork and involvement in outflow facility" Investigative Ophthalmology and Visual Science July 2011
  • "Inhibition of Hyaluronan Synthesis Reduces Versican and Fibronectin Levels in Trabecular Meshwork Cells" PLoS One November 5 2012
  • "The role of the IL-20 subfamily in glaucoma" Mediators of Inflammation  2016
  • "Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells" Scientific Reports July 28 2016
  • "Working your SOCS off" Experimental Eye Research March 2 2016
  • "Comparison of microRNA expression in aqueous humor of normal and primary open-angle glaucoma patients using PCR arrays" Investigative Ophthalmology and Visual Science June 1 2017
  • "Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)" Autophagy January 21 2016
  • "Author response" Investigative Ophthalmology and Visual Science October 1 2017
  • "Tunneling nanotubes are novel cellular structures that communicate signals between trabecular meshwork cells" Investigative Ophthalmology and Visual Science October 1 2017
  • "Glaucomatous cell derived matrices differentially modulate non-glaucomatous trabecular meshwork cellular behavior" Acta Biomaterialia January 1 2018
  • "Erratum to" Autophagy January 1 2016
  • "Consensus recommendations for trabecular meshwork cell isolation, characterization and culture" Experimental Eye Research June 1 2018
  • "Myosin-X silencing in the trabecular meshwork suggests a role for tunneling nanotubes in outflow regulation" Investigative Ophthalmology and Visual Science February 1 2019

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