Dr. Leonard Petrucelli, Ph.D. is the Ralph B. and Ruth K. Abrams Professor and Chair of the Department of Neuroscience at Mayo Clinic in Florida, and he serves as Vice Chair for the Florida Alzheimer’s Advisory Board, Chief Scientific Advisor for Target ALS, and the Scientific Advisory Board for Science Translational Medicine. Dr. Petrucelli also leads two large NIH-funded programs, including a Center Without Walls focused on identifying genetic modifiers of tauopathy, and a program project grant investigating mechanisms of disease pathogenesis linked to C9ORF72 repeat expansions, which is now the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). His laboratory has been at the forefront of research investigating the cellular mechanisms that cause neurodegeneration in diseases characterized by abnormal protein aggregation, like FTD and ALS, as well as Alzheimer’s disease (AD). Expanding upon the commitment to understand the mechanisms of disease progression and neuronal death, his recent studies now include an emphasis on translational research to identify biomarkers and develop therapies for treatment and prevention. For nearly a decade, his lab has been investigating mechanisms of tau degradation and using this knowledge to identify therapeutic strategies aimed at eliminating abnormal tau accumulation associated with AD and other tauopathies. Another primary focus of his lab is deciphering the cause of TDP-43 pathology in FTD, including the link between C9ORF72 repeat expansions and TDP-43 deposition, and determining how it can be prevented. His group recently reported that sense and antisense RNA transcribed from the C9ORF72 repeat expansion may cause neurodegeneration by two means: via the accumulation of these transcripts into discrete structures in the nucleus, termed RNA foci, and by serving as a template for the synthesis of aggregation-prone “c9RAN proteins” by repeat-associated non-ATG (RAN) translation (Neuron, Acta Neuropathologica). His team discovered that poly(GP) c9RAN proteins are detected in cerebrospinal fluid of c9FTD/ALS patients and may serve as bio/pharmacodynamic markers (Neuron), and also developed the first mouse model to exhibit both neuropathological and behavioral defects associated with c9FTD/ALS (Science). In addition to developing RNA foci and c9RAN protein pathology, these mice develop endogenous TDP-43 pathology, yet another pathological hallmark of c9FTD/ALS. As the remarkable discoveries attest, Dr. Petrucelli’s research program has grown and continuously evolved, highlighting that his laboratory is one of few studying multiple AD and related disorders.