The long-term goal of our research is to understand the cellular and molecular basis of age-associated neurodegenerative diseases, such as Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS). The major focus of our studies has been the identification of the cellular and molecular mechanisms by which specific proteins central to these diseases (e.g., the beta amyloid peptide in AD and TDP-43 in ALS) induce pathology. Our initial approach has been to develop transgenic C. elegans strains that express these human proteins, often resulting in abnormal phenotypes that can be the basis of classic genetic screens. The overall rationale for this approach is that invertebrate models allow facile "pilot" studies that are time-consuming, difficult, or impossible in other systems. However, in recent years we have shifted our studies to complement the C. elegans work by employing mammalian cell culture and bioinformatic analysis of mouse and human deep sequencing data.
Larval C. elegans worm with pan-neuronal expression of human tau protein (red) and intestinal GFP (green). Nuclei are blue.