Charles Glabe, PhD, is a professor of Molecular Biology and Biochemistry at the University of California, Irvine. The focus of the Glabe laboratory is to understand the structure of amyloids, their assembly pathways, and their mechanisms of pathogenesis in neurodegenerative disease. The goal of this work is to facilitate the development of effective diagnostic and therapeutic agents.
Dr. Glabe and his team have recently discovered that amyloids form an ensemble of common structures, including parallel, inregister fibrils, anti-parallel ß sheet prefibrillar oligomers, and ß barrel annular protofibrils. These structures display generic epitopes that are recognized by polyclonal and monoclonal antibodies in a wide variety of amyloid forming proteins and peptides. The laboratory has discovered that fibrils and prefibrillar oligomers represent alternative aggregation pathways for many different types of amyloids and that they have distinct underlying structural motifs that are generic to the particular aggregation state and are recognized by specific conformation dependent antibodies.
This raises the question of whether these different amyloid structures have distinct functions in pathogenesis. Dr. Glabe and his team have discovered that unique types of amyloid deposits accumulate at specific times and locations during aging and disease such as intracellular amyloid which aggregates early inside neurons that ultimately degenerate and form the nidus of neuritic plaques. They are currently investigating these novel amyloids to determine their significance for disease processes and their mechanisms of pathogenesis.