Salil A. Lachke, Ph.D.

Research

My laboratory investigates mammalian eye development with the aim to identify and functionally characterize genes associated with human ocular diseases. Our present efforts are directed towards understanding development of the ocular lens - a transparent tissue that focuses light on the retina for visual acuity. Lens transparency is the outcome of a specialized developmental program involving differentiation of anteriorly localized epithelial cells into posteriorly localized elongated fiber cells that make up bulk of the lens tissue. Terminally differentiated lens fiber cells express high levels of structural proteins termed crystallins and completely degrade their nuclei and organelles - properties that are necessary for rendering the lens transparent. Perturbation of this differentiation program results in opacification of the lens causing an ocular disease termed cataract. We take an integrated approach using systems biology and mouse developmental genetics to identify novel genes associated with eye development and disease. Recently, we developed the first version of a systems-based strategy termed iSyTE (integrated Systems Tool for Eye gene discovery, http://bioinformatics.udel.edu/Research/iSyTE) that has facilitated the identification and characterization of several new genes associated with cataract (e.g. TDRD7, PVRL3, SEP15). We are presently investigating the function of these and several other iSyTE-predicted candidate genes using mouse models. By integrating biological and algorithmic approaches to identify the interacting components as well as the targets of key regulatory genes like TDRD7, we intend to assemble networks of transcriptional and post-transcriptional regulators in the lens. We anticipate that these efforts will lead to the development of newer even more effective versions of iSyTE and provide insights for therapeutic interventions for ocular diseases.