Photo of Kate E Keller, Ph.D.

Kate E Keller Ph.D.

    • Research 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

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

Memberships and associations

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

Publications

  • "Comparison of microRNA expression in aqueous humor of normal and primary open-angle glaucoma patients using PCR arrays : A pilot study." Investigative Ophthalmology and Visual Science In: , Vol. 58, No. 7, 01.06.2017, p. 2884-2890.
  • "Effects of induction and inhibition of matrix cross-linking on remodeling of the aqueous outflow resistance by ocular trabecular meshwork cells." Scientific Reports In: , Vol. 6, 30505, 28.07.2016.
  • "Working your SOCS off : The role of ASB10 and protein degradation pathways in glaucoma." Experimental Eye Research In: , 02.03.2016.
  • "Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)." Autophagy In: , Vol. 12, No. 1, 21.01.2016, p. 1-222.
  • "The role of the IL-20 subfamily in glaucoma." Mediators of Inflammation In: , Vol. 2016, 4083735, 2016.
  • "Extracellular matrix in the trabecular meshwork : Intraocular pressure regulation and dysregulation in glaucoma." Experimental Eye Research In: , Vol. 133, 01.04.2015, p. 112-125.
  • "Mapping molecular differences and extracellular matrix gene expression in segmental outflow pathways of the human ocular trabecular meshwork." PLoS One In: , Vol. 10, No. 3, e0122483, 31.03.2015.
  • "Hyaluronan cable formation by ocular trabecular meshwork cells." Experimental Eye Research In: , Vol. 139, 6733, 2015, p. 97-107.
  • "Interleukin-20 receptor expression in the trabecular meshwork and its implication in glaucoma." Journal of Ocular Pharmacology and Therapeutics In: , Vol. 30, No. 2-3, 01.03.2014, p. 267-276.
  • "Intraocular pressure homeostasis : Maintaining balance in a high-pressure environment." Journal of Ocular Pharmacology and Therapeutics In: , Vol. 30, No. 2-3, 01.03.2014, p. 94-101.
  • "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 In: , Vol. 55, No. 9, 2014, p. 5497-5509.
  • "Ankyrin repeat and suppressor of cytokine signaling box containing protein-10 is associated with ubiquitin-mediated degradation pathways in trabecular meshwork cells." Molecular Vision In: , Vol. 19, 25.07.2013, p. 1639-1655.
  • "The effects of tenascin C knockdown on trabecular meshwork outflow resistance." Investigative Ophthalmology and Visual Science In: , Vol. 54, No. 8, 2013, p. 5613-5623.
  • "Inhibition of Hyaluronan Synthesis Reduces Versican and Fibronectin Levels in Trabecular Meshwork Cells." PLoS One In: , Vol. 7, No. 11, e48523, 05.11.2012.
  • "Perturbation of hyaluronan synthesis in the trabecular meshwork and the effects on outflow facility." Investigative Ophthalmology and Visual Science In: , Vol. 53, No. 8, 07.2012, p. 4616-4625.
  • "Variants in ASB10 are associated with open-angle glaucoma." Human Molecular Genetics In: , Vol. 21, No. 6, ddr572, 03.2012, p. 1336-1349.
  • "Segmental versican expression in the trabecular meshwork and involvement in outflow facility." Investigative Ophthalmology and Visual Science In: , Vol. 52, No. 8, 07.2011, p. 5049-5057.
  • "Elastic modulus determination of normal and glaucomatous human trabecular meshwork." Investigative Ophthalmology and Visual Science  In: , Vol. 52, No. 5, 04.2011, p. 2147-2152.
  • "Differential effects of ADAMTS-1, -4, and -5 in the trabecular meshwork." Investigative Ophthalmology and Visual Science In: , Vol. 50, No. 12, 12.2009, p. 5769-5777.
  • "Stem cells in the trabecular meshwork : Present and future promises." Experimental Eye Research In: , Vol. 88, No. 4, 30.04.2009, p. 747-751.
  • "Extracellular matrix turnover and outflow resistance." Experimental Eye Research In: , Vol. 88, No. 4, 30.04.2009, p. 676-682.
  • "Effects of modifiers of glycosaminoglycan biosynthesis on outflow facility in perfusion culture." Investigative Ophthalmology and Visual Science In: , Vol. 49, No. 6, 06.2008, p. 2495-2505.
  • "Specialized podosome-or invadopodia-like structures (PILS) for focal trabecular meshwork extracellular matrix turnover." Investigative Ophthalmology and Visual Science In: , Vol. 49, No. 12, 2008, p. 5353-5365.
  • "Extracellular matrix gene alternative splicing by trabecular meshwork cells in response to mechanical stretching." Investigative Ophthalmology and Visual Science In: , Vol. 48, No. 3, 03.2007, p. 1164-1172.

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