neural development and degeneration in the vertebrate neural retina
University of UtahPersonal Phone: 801-581-4984
My laboratory is focused on understanding the molecular pathways controlling neural development and degeneration in the vertebrate neural retina. The retina is one of the most accessible parts of the central nervous system, and is of critical importance since disorders of eye development can lead to congenital blindness, while degeneration of retinal neurons can cause progressive blindness at later ages. In the developing retina we are studying how eye tissues are patterned and how retinal progenitors are directed to adopt specific retina cell fates. Our goal is to define the sequence of gene expression that governs neural differentiation in the retina, and understand how extrinsic signaling pathways modulate gene expression or function. For example, we have been investigating the mechanisms by which proneural transcription factors promote retinal neuron differentiation, and how they contribute to the ordered sequence of retinal histogenesis. We find that both the expression and activity of these factors are controlled by multiple signaling pathways, as well as through epigenetic regulation. Ultimately, the goal is to reveal general principles governing the development of neural stem cells and progenitors, which may inform efforts to harness these cells for the treatment of disease and injury of the nervous system.
To investigate the process of neurodegeneration, we are probing the mechanisms underlying glaucoma, a neurodegenerative disease of the retina that is characterized by progressive loss of retinal ganglion cells leading to blindness. Using an established mouse model for glaucoma, we have documented significant involvement of the innate immune system, and found recruitment and activation of microglia at very early stages of the disease. Microglia are the resident immune surveillance cells of the CNS, and are exquisitely sensitive to neuronal stress and injury. They have been implicated in multiple neurodegenerative diseases, although their role remains controversial. We are directly testing the role of microglia in neuronal decline, and defining the signals leading to their recruitment and activation with disease progression. Our ultimate goal is to identify key molecular pathways that can be targeted to slow or prevent blindness in glaucoma.