Our lab is interested in two major questions in biology and medicine. First, in inherited neurodegenerations, we wish to understand what is happening in the mutant neurons, in the years to decades between their birth and their death years to decades later. After decades of normal function, why do the neurons suddenly die? To address this question, we are identifying molecular mechanisms that contribute to, or protect against the death of mutant photoreceptors (PRs) in inherited photoreceptor degenerations (IPDs) using mouse models of these diseases. Understanding of these mechanisms is likely to suggest therapeutic opportunities that will slow or arrest PR death. Second, we wish to understand the roles of “accessory” proteins in the regulation of ion channels in neurons, particularly at synapses. Our focus is on two such proteins that we discovered, Neto1 and Neto2. The Neto proteins are multifunctional, as indicated by their loss-of-function phenotypes, which include defects in axon guidance, seizures in some genetic backgrounds, defects in memory and learning, and abnormal regulation of neuronal excitability. To date, we have identified at least 5 ion channels or other neuronal proteins whose activity is or appears to be regulated by a Neto. Elucidation of the role of the Netos in the brain is increasing our understanding of a surprisingly broad range of fundamental neuronal processes.

Bramall, A. Wright, A., Jacobson, S. and Mclnnes, R. R. (2010). The genomic, biochemical and cellular responses of the retina in inherited photoreceptor degenerations and prospects for the treatment of these disorders. Annual Review of Neuroscience 33, 441-472. Ng, D., Pitcher,, G. M., Szilard, R. K., Sertié, A., Kanisek, M., Clapcote, S. J., Lipina, T., Kalia, L. V., Joo, D., McKerlie, C., Cortez, M., Roder, J. C., Salter, M. W., & McInnes, R. R. (2009). Neto1 is a novel CUB-domain NMDA receptor interacting protein required for synaptic plasticity and learning. PLoS Biology 7, 278-300. Erclik, T., Hartenstein, V., Lipshitz, H. D. and McInnes, R. R. (2008). Conserved role of the Vsx genes supports a monophyletic origin for bilaterian visual systems. Current Biology 18, 1278-1287.