Kun-Che Chang, PhD

My research is aimed at restoring vision loss, especially caused by glaucoma and optic neuropathy. I investigate the regulatory mechanism of RGC differentiation and apply the findings to gene and stem cell therapies.

Glaucoma and other optic neuropathies lead to damage and eventual cell death of retinal ganglion cells (RGCs). Once lost, RGCs are not replaced in humans or other mammals, resulting in irreversible blindness. Gene therapy via viral infection in retinas is the potential treatment for restoring degenerating cells and axons. Understanding the regulatory mechanism of gene therapy in neuronal regeneration suggests a potent therapeutic 
strategy for vision restoration in optic neuropathies. 
On the other hand, transplantation of stem cell-derived RGCs could be a feasible approach to restore vision; however, it is not well understood how to promote RGC differentiation from stem cells (SCs). Thus, identifying the relevant signaling pathways that promote RGC specification will be necessary to generate donor RGCs that integrate and form functional connections within recipient retinas. To date, several protocols have been reported for RGC generation from human SCs, however, these protocols are labor intensive, require significant time in culture, and yield low efficiencies of RGC production. To overcome these issues, I will develop a rapid differentiation protocol combined with a 3D retinal organoid model in hESCs to investigate the relevant signaling and/or transcription factors in RGC fate specification.