Dr. John Ash Joins Department of Ophthalmology

The University of Pittsburgh and the Eye & Ear Foundation are pleased to welcome John Ash, PhD, as the new Vice Chair and Director of Research in the Department of Ophthalmology at the University of Pittsburgh School of Medicine, effective December 1, 2022. He will hold the E. Ronald Salvitti Professor of Ophthalmology Research and Directorship of the Charles and Luella Snyder Lab. He will also have a role in the leadership of the Louis J. Fox Center for Vision Restoration.

Dr. Ash comes to Pittsburgh from the University of Florida. From 2011 on, he was the Francis M. Bullard Eminent Scholar Chair in Ophthalmic Sciences in the Department of Ophthalmology. Prior to that, he was a tenured Associate Professor in the Department of Ophthalmology at the University of Oklahoma Health Sciences Center.

Dr. Ash’s research is focused on mechanisms of vision loss from inherited retinal degeneration and age-related macular degeneration. His studies have shown that in the early stages of the disease, the retina responds to injury by inducing the expression of neuroprotective cytokines such as leukemia inhibitory factor (LIF). He also discovered that these cytokines are expressed under conditions of stress. The increased LIF is important in preventing or delaying photoreceptor or RPE cell death under chronic stress conditions, including inherited mutations known to cause blindness.

Using mouse genetic engineering, Dr. Ash’s lab has demonstrated that loss of the LIF receptor, gp130, or its signaling intermediate STAT3, results in accelerated retinal degeneration. These results have broad implications for the understanding of human inherited retinal degeneration. In humans, disease-causing genes are present before birth, but patients inheriting mutations that cause retinitis pigmentosa or age-related macular degeneration typically do not develop the disease for decades.

Dr. Ash’s work suggests that LIF and its receptor gp130 keep cells alive and functioning, and their induction delays the onset and progression of the disease. He is currently funded to identify the mechanisms by which activation of STAT3 mediates retinal protection.

In another project, Dr. Ash studied the role of metabolism in retinal degeneration. The retina has highly metabolic activity, and retinal degenerations have been associated with dysregulation of multiple metabolic pathways that lead to toxic oxidative damage. Little is known about how metabolism is maintained under normal conditions or is dysregulated in degenerating retinas. Dr. Ash found that AMPK (AMP-activated protein kinase) is a key regulator of metabolism in highly metabolic tissues and is a candidate for regulating metabolism in photoreceptors. Dr. Ash published the finding that enhancing activation of AMPK using the drug metformin reduces degeneration through an AMPK-dependent mechanism. This suggests that AMPK is an important regulator of photoreceptor metabolism and is essential to maintaining retinal health. He is currently working to identify additional therapeutic targets in the AMPK pathway.

Prior to joining the Department, he worked closely with the team, scientists, Jeff Gross, and José-Alain Sahel to prepare a smooth and efficient transition.

Support from the E. Ronald Salvitti Chair, the Eye & Ear Foundation, the Hillman Foundation, UPMC, and Pitt have made Dr. Ash’s position possible.