Overview

Mechanobiology:

The overarching theme of research in the lab is to describe how cells are able to sense and respond to physical forces and mechanics at a molecular, phenotypic, and tissue level. The process by which biophysical stimuli (such as surface topography, stiffness, electrical fields etc) are transferred to result in gene/protein expression changes is termed as Mechanotransduction. The gold standard of in vitro research in vision science is to use non-physiological culture substrates such as glass or plastic. Cells in the eye reside on immensely complex tissues with intricate 3D architecture and defined mechanical properties. My lab is particularly interested in the mechanical characterization of ocular tissues and in the mechanobiology of ocular diseases in order to develop better tools for drug and toxicity screening, identify new molecular targets, and to develop materials-based technologies for therapeutics. We are currently focused on two disease models:

(i) Glaucoma:

Ocular hypertension is an important manifestation seen in a variety of glaucoma. While, in some forms, increase in intraocular pressure is because of physical obstruction of the angle, in other forms it is due to increased resistance to aqueous humor outflow through the trabecular meshwork (TM) and Schlemm’s canal (SC). Resistance to outflow is multifactorial and has been long attributed to changes in the extracellular matrix (ECM), deposition of plaque like material, cellular drop-out, loss of intra- and inter-cellular pores, and / or collapsing of the beams. The primary goals of the lab are to characterize the biophysical properties of cells, tissues, and ECM contributing to ocular hypertension, and to understand the molecular mechanisms that underlie the bidirectional interaction between cells and their immediate microenvironment.

(ii) Ocular surface disorders:

Ocular surface disorders such as dry eye, conjunctivitis, and rosacea are a diverse group of diseases that share common attributes in that they involve changes in the cellular and tear film properties at the ocular surface interface. Replenishment of the tear film and clearance of cytotoxic constituents are mediated naturally by blinking. There are downward and tangential shear forces exerted between the cornea and eye lid. Impairments in the pre-corneal tear film result in aberrant force transfer during blinking thus subjecting the already ‘inflamed’ cells to significant shear stress, resulting in a positive feedback loop to elicit further damage. My lab is interested in document the role that mechanical shear and adverse culture environments play in maintaining a healthy ocular surface.