Peter F. Hitchcock, Ph.D.

Repairing injuries to the human brain from intrinsic cellular sources is an ambitious health care goal. A step toward realizing this goal is to study regeneration-competent vertebrate models and identify cellular and molecular mechanisms that underlie neuronal regeneration. The Hitchcock laboratory uses the zebrafish to investigate the cellular and molecular mechanisms that govern the selective death and regeneration of photoreceptors in the retina. Mammals have a limited ability to regenerate tissues, whereas zebrafish possess the ability to regenerate almost all tissues and organs, including fin, heart, kidney and brain. In the zebrafish brain, injury and cell death activate complex signaling networks that stimulate nearby radial glia to reprogram into neural stem-like cells that repair the injury. In the retina, Müller glia, radial glia unique to the retina, reprogram into stem-like cells and undergo a single asymmetric division to generate multi-potent retinal progenitors. Müller glia-derived progenitors then divide rapidly, numerically matching the magnitude of the cell death, differentiate to replace the ablated neurons and reconnect the new neurons into extant synaptic circuits. We have established that neuroinflammation plays an essential role in this multi-step process, including the reprogramming of Müller glia and proliferation among the Müller glia-derived progenitors. We use genome editing techniques, unique zebrafish lines and advanced microscopy to determine how microglia, macrophages unique to the CNS, regulate the inflammatory milieu within the retina and how inflammatory molecules govern the key events during photoreceptor regeneration. The overarching goal of the lab is to identify mechanisms that govern stem cell-based neuronal regeneration in the vertebrate central nervous system and provide mechanistic insights into the consequences of neuroinflammation in human retinal disease.