The long-term goal of my research is to understand the cellular and molecular basis of age-associated neurodegenerative diseases, particularly Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS). Towards this goal, I was the first researcher to develop a transgenic invertebrate model for a human neurodegenerative disease, by engineering C. elegans to express human b-amyloid peptide (Link, 1995). My lab's work in C. elegans demonstrated that TDP-43, a central player in ALS/FTD pathology, limits the accumulation of double-stranded RNA (dsRNA) (Saldi et al, 2014). As mammalian models have improved, and genetic studies have implicated vertebrate-specific functions (e.g., microglia and neuroinflammation) in neurodegenerative diseases, my lab has shifted its focus to mammalian cell culture, human brain immunohistochemistry, and transcriptome analyses, including work with human iPSCs and human brain sequence data.
keywords
modeling human neurodegenerative diseases using cellular and C. elegans models
