The Ash Lab

John D. Ash, Ph.D.Dr. Ash’s research is focused on both understanding the cause of blindness due to retinal degeneration and developing therapies to prevent loss of sight.  His research is relevant to inherited retinal degenerations such as retinitis pigmentosa, cone-rod dystrophies, LCA, or age related macular degeneration. His most recent studies have shown the important contribution of endogenously expressed cytokines such as leukemia inhibitory factor (LIF).  His work has shown that these cytokines are expressed under conditions of stress, and that the increased LIF is important to prevent or delay photoreceptor or RPE cell death under chronic stress conditions, including inherited mutations known to cause blindness.  By using mouse genetic engineering, his lab has demonstrated that loss of the LIF receptor, gp130 or it’s signaling intermediate STAT3, results in accelerated retinal degeneration.  The results from this work have broad implications in the understanding of human inherited retinal degeneration.  In humans, disease-causing genes are present before birth; however patients inheriting those mutations that cause retinitis pigmentosa or age related macular degeneration typically do not develop disease for 40 to 80 years.  Dr. Ash’s work suggests that LIF and its receptor gp130 keep cells alive and functioning, and serve to delay the onset and progression of disease.  Variation in efficiency of this internally protective activity could also be a partial explanation of why family members who inherit the same mutation can have a wide range in the age of onset and severity of disease.   This work has led to the identification of drug targets to promote cell survival, and has led to the development of several gene therapy approaches to specifically enhance the survival of photoreceptors and RPE which are now being tested in models of disease.