Derek S. Welsbie, MD, PhD

Assistant Professor of Ophthalmology, University of California, San Diego

Research: “Glaucoma Neuroprotection: Rho-associated kinase 2 (ROCK2) as an Upstream Activator of Dual-Leucine Zipper Kinase (DLK) in Response to Axonal Injury”

Research

Glaucoma is a neurodegenerative disease of retinal ganglion cells (RGCs), the neurons responsible for processing and transmitting visual information from the retina to the brain. In response to axon injury at the optic nerve head, these cells activate genetic programs that lead to axon degeneration, cell death and ultimately, permanent vision loss. The current treatments focus on reducing the injury at the optic nerve head by lowering intraocular pressure but this can be difficult in some patients while others worsen despite low pressures. My lab has been interested in developing neuroprotective strategies that could complement pressure lowering by directly interfering with the RGC-intrinsic degeneration pathways. To identify promising targets in a global and relatively unbiased manner, we conduct high-throughput functional genomic screens using mouse primary RGCs and human stem cell-derived RGCs. This work previously identified dual leucine zipper kinase (DLK) as a key mediator of RGC cell death in vitro and in vivo. We are now in the process of validating other hits nominated by the screens, including putative upstream and downstream regulators of DLK-dependent cell death. Finally, we seek to validate DLK as a neuroprotective target in glaucoma and other neurodegenerations.

Publications

Derek S. Welsbie, MD, PhD, publications