Leonard Petrucelli

Leonard Petrucelli, Ph.D., is a Professor of Neuroscience and a Consultant in the Department of Neuroscience at Mayo Clinic in Jacksonville, Florida. He leads the Neurodegenerative Diseases Laboratory, which is dedicated to understanding the cellular and molecular mechanisms underlying neurodegenerative disorders such as Alzheimer's disease, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS). His research is highly translational, focusing on identifying therapeutic targets and developing biomarkers for diagnosis and disease monitoring.

Dr. Petrucelli's research interests center on protein aggregation, RNA metabolism, and neurodegeneration. His lab investigates the role of TDP-43 and tau proteinopathies, the significance of c9RAN proteins in C9orf72-related disorders, and the development of novel therapeutic agents. His team employs a multidisciplinary approach, utilizing cell biology, induced pluripotent stem cell (iPSC) technology, transcriptomics, and mouse modeling to elucidate disease mechanisms and translate findings into potential clinical applications.

The recent body of work from Dr. Petrucelli's lab demonstrates a strong focus on the molecular underpinnings of ALS and FTD, particularly the role of TDP-43 mislocalization, cryptic splicing, and dipeptide repeat proteins from the C9orf72 mutation. His research also extends to tauopathies, exploring mechanisms of tau seeding and propagation, and identifying common pathological features across neurodegenerative diseases, such as TMEM106B fibrillization. A significant trend is the identification of novel therapeutic targets and biomarkers, reflecting his lab's commitment to translational neuroscience.

Scientific Awards and Professional Highlights:

• Award on the Aging Nervous System; Robert and Arlene Kogod Center on Aging, Department of Neuroscience and Department of Neurology; Mayo Clinic; 2024
• Ralph B. and Ruth K. Abrams Professor, Mayo Clinic, 2015
• "Best Advances of 2013" for discovery of c9RAN proteins, Neurology Today
• Invited member, NIH Cellular and Molecular Biology of Neurodegeneration study section, 2011-2016
• Director of NIH P01NS084974 grant on C9orf72 pathobiology
• Member, Alzheimer's Disease Research Grant Advisory Board, Florida Department of Health, 2014
• Health Care Heroes award for research, Jacksonville Business Journal, 2014
• Scientific Advisory Board, Alzforum, 2007-2009

Dr. Petrucelli is a principal investigator on multiple active grants from the National Institute of Neurological Disorders and Stroke (NINDS) and the Alzheimer’s Association, funding projects on TMEM106B, tau mouse models, and C9orf72 and tau toxicity. His lab is a hub for collaborative research, working with institutions like Scripps Florida, and actively seeks new collaborations and training opportunities for postdoctoral fellows.

Laboratory and Research Focus: The Neurodegenerative Diseases Laboratory uses cutting-edge techniques to model genetic lesions in mice, map RNA defects, and develop high-throughput biomarker assays. The lab's work on c9RAN proteins and tau seeding has been groundbreaking, and its current projects aim to pinpoint therapeutic strategies for inhibiting nerve degeneration in complex neurodegenerative disorders.