Dr. Leonard Petrucelli is the Center Director, Co-PI for Project 2, and PI of Core A (Administration Core). With his proven leadership as Chair of the Department of Neuroscience at the Mayo Clinic and director of a program project grant (NINDS) focused on pathomechanisms of the C9ORF72 repeat expansion, Dr. Petrucelli will guide the research focus and direction and our Center with assistance from the External Advisory Committee. Dr. Petrucelli has demonstrated scientific and administrative excellence and is uniquely positioned to lead and maintain the quality of the Projects and Cores. His laboratory has been at the forefront of research investigating cellular mechanisms that cause neurodegeneration in diseases characterized by abnormal protein aggregation, such as frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and Alzheimer’s disease (AD). In fact, Dr. Petrucelli was recently awarded a prestigious R35 Research Program Award (NINDS) in recognition of the strength and transformative nature of his program focused on the diverse underlying mechanisms of FTLD.

Dr. Gerry Schellenberg is Co-PI of Project 1. Dr. Schellenberg has extensive experience in human molecular genetic studies that include linkage analysis and other family-based methods, genome-wide association studies, and mutation and variant detection with Sanger-based and Next Generation-based DNA sequencing methods. Throughout his career, he has been highly productive with over 300 peer-reviewed publications, most related to human disease genetics and incorporating the development and utilization of various model organisms. His main research interest is neurodegenerative diseases, particularly AD and PSP, though he also works on the genetics of autism. His most recent work focuses on genome-wide association studies and discovery of rare variants by rare-variant genotyping arrays, Haplotype Reference Consortium imputation, and Next Generation sequence data.

Dr. Owen Ross is Co-PI for Project 1. Dr. Ross is an Associate Professor and Consultant within the Department of Neuroscience at the Mayo Clinic, and his main research focus is the genetics of Parkinsonism and related movement disorders. He has published over 200 articles on the genetics of aging and age-related neurodegenerative disease, and has received numerous foundation and federal grants, including NIH R01 funding focused on MAPT genetic variation in disease. Dr. Ross is also Director of the Genetic Core within the Mayo Clinic Udall Center of Excellence for Parkinson’s Disease Research. His recent work includes the publication of the first genome-wide association study in the tauopathy corticobasal degeneration (CBD), as well as the identification of MAPT A152T as a risk factor for Lewy body dementia. Dr. Ross is also part of a number of on-going Next-Generation Sequencing consortia efforts for Parkinson’s disease (PD), PSP, and CBD.

Dr. Cat Lutz is Co-PI of Project 2. Dr. Lutz has had scientific, operational and financial oversight of the Mouse Repository at The Jackson Laboratory (JAX) since 2008, being appointed Director in 2011. In 2012, Dr. Lutz launched the Rare and Orphan Disease Center at JAX, where she began working with multiple disease foundations and academic institutes to genetically engineer and procure mouse strains of biological and preclinical relevance to particular diseases. In 2013, Dr. Lutz established a new program at JAX for in vivo pharmacology services to test therapeutics in mouse models of neurological disease for biotech and pharmaceutical companies. She has more than 25 years of experience in mouse genetics and characterization of neurological phenotypes in mice. As part of the greater mouse repository effort, Dr. Lutz will facilitate the rapid characterization, standardization and consistent use of mouse models, with the aim of supporting reproducibility across laboratories and accelerating treatment discovery. Dr. Lutz has oversight of a growing collection of more than 8,500 unique strains (including over 1,700 live colonies) that are made available for distribution to the scientific community. Within the Genetic Resource Science department at JAX, Dr. Lutz has oversight of a team of 130 employees with grants and administrative budgets greater than $30M/year. Dr. Lutz also runs her own research laboratory at JAX with approximately 25 lab members. As a neuroscientist by training, her scientific interests are in the development of mouse models for different neurological diseases. Her lab has played a significant role in helping to establish and phenotypically validate disease-specific mouse resources that allow for cross comparative, longitudinal studies across a series of models. Her primary research focus is in diseases of motor neuron degeneration, including spinal muscular atrophy (SMA) and ALS. With the discovery of genetic loci that contribute to the susceptibility uncovered in human sequencing experiments, her lab has been using genome-editing technologies to engineer mouse models for ALS. Her recent publications in Neuron and Science involve the engineering of C9ORF72 models of ALS and frontotemporal dementia (FTD) and the incorporation of new genome editing technologies to rapidly create mouse models based on human mutation discovery.

Dr. Dennis Dickson is Co-PI of Core C (Human Validation Core). Dr. Dickson is a Professor in the Departments of Pathology & Neuroscience at Mayo Clinic Jacksonville. Not only does he direct the brain bank for CurePSP, but he is also the director of the brain bank for neurodegenerative disorders at Mayo Clinic Jacksonville, which houses over 6000 specimens, including more than 2200 cases of AD, about 1400 cases with Lewy-related pathology, about 1200 cases of tauopathy (mostly PSP and CBD), and a growing collection of FTLD and ALS (over 300 cases), as well as over 240 control cases with minimal neurodegenerative pathology. He received the Potamkin prize and MetLife awards, among others, including an endowed professorship, in recognition of his innovative work. His research focuses on the neuropathology in the brain in normal aging, AD and non-AD neurodegenerative disorders, such as Lewy body dementia, PSP, CBD, ALS, and FTLD. He has contributed to over 130 publications on the neuropathologic characterization of neurodegenerative tauopathies and has made several ground-breaking genetic discoveries, including identifying novel mutations in the tau gene (MAPT) and genome wide association studies.

Dr. Casey Cook is Co-PI of Core C (Human Validation Core). Dr. Cook (Core C) is an Assistant Professor in the Department of Neuroscience at Mayo Clinic Jacksonville, and her main research focus is understanding the mechanisms of neurodegeneration in tauopathies. Her efforts to develop a more versatile model of tauopathy utilizing somatic brain transgenesis have enabled the studies proposed in Project 2. In addition, she developed several tau immunoassays using the MesoScale Discovery platform, which will facilitate the high-throughput screening of large volumes of samples to identify mouse strains sensitive and resistant to tauopathy (Project 2). Her expertise in assay development and characterization will be essential to the activities of Core C, and she will work closely with Dr. Dickson to thoroughly investigate each target of interest to determine novel and informative endpoints that could be created to assess changes in function.

Dr. Anthony Fitzpatrick is the PI of Project 3 (competitive supplement). Dr. Fitzpatrick is an Assistant Professor in the Department of Biochemistry and Molecular Biophysics at Columbia University. The Fitzpatrick lab aims to relate the atomic structure of tau fibril polymorphs directly to biophysical properties responsible for their propagation in vivo using a range of biophysical techniques. He recently determined the atomic structures of tau fibril polymorphs purified directly from AD brain (published in Nature), and his previous studies revealed that amyloid fibril polymorphs have diverse surface properties, thermodynamic stabilities, and material properties. While high-resolution structure determination of amyloid fibrils was previously not possible using cryo-EM, Dr. Fitzpatrick has successfully incorporated advanced image-processing algorithms with state-of-the-art cryo-EM imaging techniques to successfully solve the structure of AD tau filaments. Using this expertise, Dr. Fitzpatrick will now examine the role of genetic factors, such as mutations in the tau gene (MAPT), in determining filament morphology and influencing phenotypic variation in neurodegenerative tauopathies.