Dr. Petrucelli and his research team are leaders in the study of neurodegenerative diseases, focusing on Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD). Their work bridges fundamental research on disease mechanisms with the development of therapeutic targets and biomarkers. The team has made groundbreaking contributions to understanding c9orf72-mediated ALS and FTD, including being among the first to describe RAN translation and antisense pathology in these conditions. They developed the first mouse model to replicate behavioral and neuropathological features of these diseases and characterized key biomarkers, solidifying their leadership in the field.
The lab has also spent over a decade studying TDP-43 and tau-related disorders, with emerging research emphasizing aberrant TDP-43-mediated cryptic splicing in ALS/FTD and its implications for biomarker discovery. Recent investigations have focused on TMEM106b, a lysosomal gene implicated in FTD, exploring its role in disease risk through the accumulation of TMEM106b fibrils. Supported by the Kissick Family Foundation, Dr. Petrucelli and his collaborator, Dr. Michael Ward (NIH), will develop model systems investigating how TMEM106B fibrils form, what their cellular impact is, and what role they play in pathogenesis.