Research Information
Research Interests
Currently my lab focuses on understanding the molecular and cellular signaling mechanisms of aqueous humor outflow physiology. The major aspect of the study is to understand the regulation of cell-cytoskeleton-matrix interactions and intraocular pressure (IOP) regulatory proteins.
Additionally, we are performing studies to pin down the mechanistic regulation and role of ECM in the aqueous humor outflow pathway using various tools including global approaches like proteomics, as well as molecular biology along with electrophysiology and microscopy to answer the scientific questions under our realm of research.
Towards this aim, we have identified clusterin, a chaperone protein, as an important regulator of IOP. We utilize recombinant adenovirus expressing full length glycosylated secretory clusterin (AdCLU) to constitutively express clusterin.
In addition, we have also developed adenoviral constructs with mutations in human clusterin that lacks complete glycosylation of clusterin. Using AdCLU expression, we have identified that clusterin modulates the extracellular matrix homeostasis in the trabecular meshwork and the intraocular pressure.
We utilize cadaveric human anterior segment perfusion system ex vivo and knockout mice lines to test our hypothesis. We are currently investigating: a) the role of clusterin and cathepsins (cysteine lysosomal proteases) in the regulation of ECM, aqueous humor outflow resistance, and IOP, and b) direct delivery of clusterin into the anterior chamber can reverse pathological ocular hypertension.
I have been funded by Eversight Eye and Vision Research Grant, the 2018 Frank Stein and Paul S. May Grant for Innovative Glaucoma Research from The Glaucoma Research Foundation (Shaffer Grant), and the Core Utilization Pilot Grant Award from the Clinical and Translational Science Collaborative, Case Western Reserve University.