Gene Networks that Regulate Ganglion Cell Death and Axon Regeneration

Project Summary

These studies will distinguish new mechanisms responsible for cell death versus axon regeneration by investigating downstream transcriptional mechanisms of DLK and LZK. Therapies that inhibit DLK/LZK signaling show strong RGC neuroprotection in mouse models, but the lack of axon regenerative competence is a key obstacle to the utility of such treatments to restore vision in patients. I will focus on candidate transcription factors downstream of DLK and LZK and will allow me to manipulate transcriptional mechanisms to differentially regulate RGC death and axon regeneration. Clinical therapies for glaucoma are limited by our insufficient knowledge of how the disease triggers RGC death. Recent studies in animal models have identified enzymes (protein kinases) that directly link the axonal injury to apoptosis, and while blocking these signaling events is neuroprotective, these therapies eliminate the ability for cells to regrow and reconnect to the brain which is essential for visual repair. My work will investigate how RGCs regulates cell death versus axon regeneration through transcriptional networks and can identify novel targets.