SCIENCE

Blindness and visual impairment from ocular surface disorders affect over 23 million people globally, making it the second most common cause of blindness worldwide. Preventable cases of vision loss often result from wounds that heal with opacification of the ocular surface. Understanding the pathways that regulate wound healing is critical to identifying therapeutic targets that may be helpful in promoting wound healing that preserves vision. Given biological similarities between wound healing and neoplasia, examination of these pathways will also provide new insights into the growth of ocular tumors. Therefore, the major overarching goal of the Lee Lab is to investigate wound healing in the context of tumorigenesis to provide comprehensive knowledge of molecular pathways that will lead to new potential therapies.

Currently, the Lee Lab is focused on three projects:

1) Investigating the role of SFK in corneal epithelial wound healing: Most of our knowledge on the roles of Src-Family Kinases (SFK)  in wound healing and tumorigenesis has been from skin studies. Although EGFR activation in corneal epithelial biology has been established, the significance of SFKs, downstream effectors of EGFR, and SFK-activating signaling molecule (Srcasm), a negative regulator of SFK activity, in corneal epithelial wound healing and tumors have not been examined. One of the goals of the Lee Lab is to determine the roles of SFK and Srcasm in ocular surface wound healing and tumorigenesis. Our approach includes novel genetically engineered mouse models and lentiviral constructs to manipulate Fyn, and SFK member, and Srcasm levels; human ocular surface tumor specimens for molecular and transcriptional profiling; and in vitro human organotypic model and epithelial cultures.

2) Establishing the role of NMDAR in corneal nerve regeneration: Corneal diseases continue to be a major health problem in the US, and many of these diseases result in permanent damage to the corneal nerves, leading to a dysfunctional cornea. Given the increasing incidence of corneal diseases, it is imperative to understand the molecular mechanisms involved in corneal nerve regeneration and identify novel therapeutic targets. Glutamate receptors, such as N-Methyl-D-aspartate receptors (NMDAR), have been shown to enhance nerve regeneration in other analogous systems. Therefore, one major project of the Lee Lab is to use novel genetic, molecular, and therapeutic approaches to study and define the role of NMDAR in corneal nerve regeneration and its potential as a novel drug target. 

3) Creating a comprehensive database on corneal sensory nerves: The Lee Lab is part of a multi-PI collaborative project focused on characterizing the sensory afferents that innervate the ocular surface morphologically, molecularly, and functionally. This project implements cutting-edge genetic mouse models, advanced microscopy, single-cell genomics, and machine-learning approaches. The goal is to provide an extensive, detailed resource to inform the physiology and pathophysiology of the corneal nerve afferents and inform the development of new treatments for diseases, such as dry eye disease, neurotrophic keratitis, and neuropathic ocular pain.