Dr. Padmanabhan Pattabiraman obtained his Bachelors and Masters majoring in Biochemistry from Tamil Nadu, India. He obtained his PhD in Neuroscience from the International School for Advanced Studies (SISSA), Trieste, Italy. His thesis was on understanding the role of neurotrophic factors - brain derived neurotrophic factor and neurotrophin 4/5 - in visual cortical plasticity.
During the post-doctoral training at Duke University in the lab of Dr. Vasanth Rao, he demonstrated the importance of potential molecular interactions between actomyosin-based contractile activity and extracellular matrix. His work identified the effects of Rho GTPase on mechanotransduction and in regulation of ECM synthesis and contractile activity within the AH drainage pathway and in homeostasis of aqueous humor outflow.
To successfully study the role Rho GTPase in regulating cell-cytoskeleton and cell matrix interactions, he generated a rodent model of ocular hypertension by overexpressing constitutively active RhoA. This model provided the proof-of-concept that constitutively active RhoA induces fibrogenic activity, which leads to ocular hypertension in a Rho kinase-dependent manner. Inhibition of Rho signaling by Rho kinase inhibitor decreased the IOP via decreasing the ECM deposition. Further, during his training at Duke, he was part of the team involved in the preclinical testing of the RhopressaTM (Netarsudil) from Aerie Pharmaceuticals. Rhopressa is currently the first FDA-approved ROCK inhibitor that improves trabecular meshwork outflow.
At Case Western Reserve University as a Research Track Investigator, lab focused on understanding the molecular and cellular signaling mechanisms of aqueous humor outflow physiology. He utilized proteomics of aqueous humor during ocular development to look into the protein profile of normal aqueous humor and how it changes during development with IOP. His lab has identified clusterin, a secretory chaperone protein, as an important cell-cytoskeleton-matrix interactions and IOP regulatory protein.
Dr. Pattabiraman joined Glick Eye Institute in Aug 2019 and has a secondary appointment in the Department of Biochemistry and Molecular Biology. His lab focuses on the following three lines of research:
Understanding the role of mechanobiology in ocular tissues and importantly in the regulation of aqueous humor outflow regulation. This project mainly deals with examining the molecular mechanisms involved in the regulation of extracellular matrix production, remodeling, and degradation in the aqueous humor outflow pathway.
Currently his R01 is to understand the role of chaperone protein clusterin in aqueous humor outflow physiology. Clusterin is a secretory chaperone protein found in the aqueous humor and produced by trabecular meshwork, iris, ciliary body and other ocular tissues. Clusterin plays an important role in regulating cell-cell adhesion and cell-substratum/matrix interactions. The levels of clusterin mRNA has been shown to be lowered in POAG and the biochemical and functional interactome of genes implicated in ocular hypertension reveal a putative linkage of clusterin gene in the POAG pathogenesis. Yet very little is known about the role of clusterin in outflow biology. They are studying mechanistic role of clusterin in IOP regulation.
Structure and function of trabecular outflow tissues differ between people of African and European Descent. Lacking is knowledge of differences in the ECM architecture and compaction in normal and POAG eyes in AD and ED. We will couple structure of the TM (molecular and cellular) with its function (outflow facility) in non-glaucomatous and glaucomatous donor eyes to identify differences in ocular physiology among AD and ED.
Sai Supriya Vuda - Research Analyst - Graduated from Case Western Reserve University.
Dr. Avinash Soundararajan - Postdoctoral Fellow - Graduated from Deakin University, Australia in June 2019.
Funding source: NIH/NEI - R01; 2018 Frank Stein and Paul S May Grant for Innovative Glaucoma Research from The Glaucoma Research Foundation (Shaffer Grant);
Eversight Vision Research Grant; CTSC grant from Case Western Reserve University.