Speaker: Jeff Mumm, associate professor of ophthalmology at Johns Hopkins University School of Medicine

Title: "Inducible models of neurodegenerative disease"

Abstract: The nitroreductase (NTR)-prodrug system of targeted cell ablation that we adapted to zebrafish has expanded investigations of cell function and cellular regeneration. However, use of this method as a means of modeling degenerative disease has been limited by the assumption that the mechanism of cell death is artificial in nature. Prior studies suggested treatments with the prodrug metronidazole (Mtz) cause NTR-expressing cells to undergo apoptosis. More recently, we found evidence that treating NTR-expressing rod photoreceptors with Mtz led to a DNA-damage induced type of cell death termed, parthanatos. Parthanatos, which is mediated by Poly(ADP-ribose)polymerase (PARP), has been strongly implicated in Parkinson’s disease and retinal dystrophies causing rod photoreceptor loss. Thus, the mechanism of cell death elicited by NTR/Mtz, be it apoptosis or parthanatos, appears to have relevance to neurodegenerative disease. As the system is inducible and titratable, we posit it may provide a powerful means of investigation how the extent, duration, and specificity of cell death impact degenerative and regenerative processes in the nervous system.

Host: Maura McGrail, Department of Genetics, Development and Cell Biology associate professor