Research in the Vidal Lab
The Vidal lab has a long-standing interest in the molecular basis of neurodegenerative diseases. We study disorders of protein conformation, in which a normal or mutated protein adopts an abnormal conformation, leading to neurodegeneration. The main goal of our work is to provide an understanding of the pathological process while assessing whether common molecular mechanisms exist between these disorders. We use a combination of biochemical, genetics, cell culture and animal model approaches to investigate the role of the abnormal proteins in disease. Current work in our lab aims at characterizing the structure of the abnormal proteins deposited in the brain of affected individuals and in animal models, assessing how these diseases propagate in the central nervous system, and the development of novel in vitro and in vivo systems in which to study pathogenic mechanisms. To this end, the laboratory is developing cellular and animal models to study neuronal and microglial function related to neurodegeneration.
Principal Investigator
Ruben Vidal, PhD, is the Luella McWhirter Martin Professor of Clinical Alzheimer's Research at IU School of Medicine Department of Pathology and Laboratory Medicine. Before joining IU, Dr. Vidal was an assistant professor at the Department of Pathology at New York University Grossman School of Medicine. Dr. Vidal is an expert in cerebral amyloid proteins and leader in dementia research. His research interests focus on the identification of the mechanism(s) responsible for neurodegeneration associated with amyloid in cerebral amyloidoses (Aβ in Alzheimer disease, ABri and ADan in Familial British and Danish dementia, and APrP in Prion diseases), and Tau in Tauopathies, the development of novel murine animal models, the structural basis of proteins involved in neurodegenerative diseases, and the identification of biomarkers and new molecular therapeutics for neurodegenerative diseases. His work has led to more than 100 peer-reviewed publications, over 30 book chapters and reviews, and continuous funding from the National Institutes of Health (NIH) for over 25 years. Dr. Vidal’s is the principal investigator of multiple NIH supported research projects and has received the Alzheimer’s Association’s Zenith Fellows award, which funds innovative scientific research. He was also awarded grants from the American Federation for Aging Research (AFAR), the American Health Assistance Foundation (AHAF, now Bright Focus), and the Alzheimer’s Association.
View Dr. Vidal’s publications:
Current Lab Members
Dr. Holly J. Garringer, Associate Research Professor of Pathology & Laboratory Medicine. PhD degree (2007) from the Department of Medical and Molecular Genetics, Indiana University, USA.
Dr. Grace I. Hallinan, postdoctoral fellow. PhD degree (2017) from University of Southampton, UK.
Dr. Anllely Fernandez, postdoctoral fellow. PhD degree (2020) from Universidad de los Andes, Chile.
Dr. Sadhana Nirwal, postdoctoral fellow. PhD degree (2023) from Indian Institute of Technology Hyderabad, India.
Dr. Alexandra Moreno-Garcia, postdoctoral fellow. PhD degree (2022) from Autonomous University of Madrid, Spain.
Important Lab Publications
-
Structures of filaments from Pick’s disease reveal a novel tau protein fold. B Falcon, W Zhang, AG Murzin, G Murshudov, HJ Garringer, R Vidal, et al. Nature 561 (7721), 137-140, 2018 doi: 10.1038/s41586-018-0454-y.
-
Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. B Falcon, J Zivanov, W Zhang, AG Murzin, HJ Garringer, R Vidal, et al. Nature 568 (7752), 420-423, 2019 doi: 10.1038/s41586-019-1026-5.
-
A stop-codon mutation in the BRI gene associated with familial British dementia. R Vidal, B Frangione, A Rostagno, S Mead, T Révész, G Plant, J Ghiso. Nature 399 (6738), 776-781, 1999 doi: 10.1038/21637.
-
Structure-based classification of tauopathies. Y Shi, W Zhang, Y Yang, AG Murzin, B Falcon, A Kotecha, M van Beers, et al. Nature 598 (7880), 359-363, 2021 doi: 10.1038/s41586-021-03911-7.
-
Novel tau filament fold in corticobasal degeneration. W Zhang, A Tarutani, KL Newell, AG Murzin, T Matsubara, B Falcon, et al. Nature 580 (7802), 283-287, 2020 doi: 10.1038/s41586-020-2043-0.
-
Cryo-EM structures of amyloid-β and tau filaments in Down syndrome. A Fernandez, MR Hoq, GI Hallinan, D Li, SR Bharath, FS Vago, X Zhang, KA Ozcan, KL Newell, HJ Garringer, W Jiang, B Ghetti, R Vidal. Nature Structural & Molecular Biology, 1-7, 2024 doi: 10.1038/s41594-024-01252-3.
-
Cryo-EM structures of amyloid-β 42 filaments from human brains Y Yang, D Arseni, W Zhang, M Huang, S Lövestam, M Schweighauser, et al. Science 375 (6577), 167-172, 2022 doi: 10.1126/science.abm7285.
-
Age-dependent formation of TMEM106B amyloid filaments in human brains. M Schweighauser, D Arseni, M Bacioglu, M Huang, S Lövestam, Y Shi, et al., Nature 605 (7909), 310-314, 2022 doi: 10.1038/s41586-022-04650-z.
-
A decamer duplication in the 3′ region of the BRI gene originates an amyloid peptide that is associated with dementia in a Danish kindred. R Vidal, T Révész, A Rostagno, E Kim, JL Holton, T Bek, M Bojsen-Møller, et al. Proceedings of the National Academy of Sciences 97 (9), 4920-4925, 2000 doi: 10.1073/pnas.080076097.
-
Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI2. R Vidal, AG Barbeito, L Miravalle, B Ghetti. Brain Pathology 19 (1), 58-68, 2009 doi: 10.1111/j.1750-3639.2008.00164.x.
-
Amino-terminally truncated Aβ peptide species are the main component of cotton wool plaques. L Miravalle, M Calero, M Takao, AE Roher, B Ghetti, R Vidal. Biochemistry 44 (32), 10810-10821, 2005 doi: 10.1021/bi0508237.
-
Structures of α-synuclein filaments from human brains with Lewy pathology. Y Yang, Y Shi, M Schweighauser, X Zhang, A Kotecha, AG Murzin, et al. Nature 610 (7933), 791-795, 2022 doi: 10.1038/s41586-022-05319-3.
-
Structure of Tau filaments in Prion protein amyloidoses. GI Hallinan, MR Hoq, M Ghosh, FS Vago, A Fernandez, HJ Garringer, R Vidal, W Jiang, B Ghetti. Acta Neuropathologica 142(2):227-241, 2021 doi: 10.1007/s00401-021-02336-w.
-
Cryo-EM structures of prion protein filaments from Gerstmann–Sträussler–Scheinker disease. GI Hallinan, KA Ozcan, MR Hoq, L Cracco, FS Vago, SR Bharath, D Li, M Jacobsen, EH Doud, AL Mosley, A Fernandez, HJ Garringer, W Jiang, B Ghetti, R Vidal. Acta Neuropathologica 144 (3), 509-520, 2022 doi: 10.1007/s00401-022-02461-0.
-
Cryo-EM structures of tau filaments from Alzheimer’s disease with PET ligand APN-1607. Y Shi, AG Murzin, B Falcon, A Epstein, J Machin, P Tempest, KL Newell, et al. Acta Neuropathologica 141, 697-708, 2021 doi: 10.1007/s00401-021-02294-3.