George S. Bloom | University of Virginia School of Medicine

Bio & Overview

Research in our laboratory is now focused primarily on Alzheimer’s disease (AD), the most common form of a group of neurodegenerative disorders known collectively as tauopathies. The histopathological hallmark of AD is the presence in brain of extracellular plaques of amyloid-β (Aβ) peptide fibrils, and intraneuronal neurofibrillary tangles, which are filaments composed of the protein, tau, and are found in all tauopathies. Despite the conspicuous appearance of plaques and tangles, a growing body of evidence points to their building blocks, Aβ and tau oligomers, as being the toxic molecular species that cause AD. For example, we have found that tau expression is required for several adverse effects of Aβ oligomers on neurons, including microtubules loss, ectopic re-rentry into the cell cycle, cytotoxicity and impaired mitochondrial activity. The goals of our work are to decipher the metabolic links that connect Aβ and tau to damage neurons, to define the structures and pathological properties of various types of Aβ and tau oligomers, and to leverage our basic science findings to develop more effective therapeutic and diagnostic tools for AD.

Academic Information

Department: Biology

Academic Title: Professor

Primary Education

BA, Biology, History, University of Pennsylvania, 1973
PhD, Biology, University of Pennsylvania, 1979
Postdoc, Cell Biology, University of North Carolina, 1980
Postdoc, Cell Biology, Worcester Foundation for Exp. Biol, 1984

Other Appointments

PhD mentor, Pathology
Professor, Cell Biology
Professor, Neuroscience
Professor, Neuroscience
PhD mentor, Pharmacology
Professor, MCDB
Professor, MOMD

Other Affiliations

Professor, Arts & Sciences
Member, Cancer Cell Signaling Program
BIMS-NESC
Pharmacology
Biology
Biology
BIMS-CDB
Cell Biology
Cell Biology
Pathology (Experimental)
Pathology (Experimental)
BIMS-MSTP
MSTP
PhD mentor, BIMS
Professor, BIMS
Neuroscience Graduate Program
Neuroscience Graduate Program
Brain Institute

Research Interests

Pathogenic mechanisms in Alzheimer's Disease and other neurodegenerative disorders

Research Disciplines

Biochemistry
Cell and Developmental Biology
Experimental Pathology
Neuroimmunology
Neuroscience

Research Opportunities

Experimental Pathology
Molecular and Systems Neuroscience
Neuroscience

PhD Programs

Experimental Pathology
Neuroscience

Selected Publications

2022

Norambuena, A., Sun, X., Wallrabe, H., Cao, R., Sun, N., Pardo, E., . . . Bloom, G. S. (2022). SOD1 mediates lysosome-to-mitochondria communication and its dysregulation by amyloid-β oligomers. NEUROBIOLOGY OF DISEASE, 169. doi:10.1016/j.nbd.2022.105737

2019

Sharlow, E. R., Koseoglu, M. M., Bloom, G. S., & Lazo, J. S. (2020). The Promise and Perils of Compound Discovery Screening with Inducible Pluripotent Cell-Derived Neurons. ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, 18(2), 97-103. doi:10.1089/adt.2019.914

Koseoglu, M. M., Norambuena, A., Sharlow, E. R., Lazo, J. S., & Bloom, G. S. (2019). Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer. JOURNAL OF ALZHEIMERS DISEASE, 67(1), 1-11. doi:10.3233/JAD-180874

2018

Norambuena, A., Wallrabe, H., Cao, R., Wang, D. B., Silva, A., Svindrych, Z., . . . Bloom, G. S. (2018). A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-β oligomers. EMBO JOURNAL, 37(22). doi:10.15252/embj.2018100241

Khan, S. S., LaCroix, M., Boyle, G., Sherman, M. A., Brown, J. L., Amar, F., . . . Lesne, S. E. (2018). Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons. ACTA NEUROPATHOLOGICA, 136(4), 589-605. doi:10.1007/s00401-018-1886-z

Kodis, E. J., Choi, S., Swanson, E., Ferreira, G., & Bloom, G. S. (2018). N-methyl-D-aspartate receptor-mediated calcium influx connects amyloid-β oligomers to ectopic neuronal cell cycle reentry in Alzheimer's disease. ALZHEIMERS & DEMENTIA, 14(10), 1302-1312. doi:10.1016/j.jalz.2018.05.017

Bloom, G. S., & Norambuena, A. (2018). Alzheimer's disease as a metabolic disorder. OCL-OILSEEDS AND FATS CROPS AND LIPIDS, 25(4). doi:10.1051/ocl/2018044

2017

Bloom, G. S., Lazo, J. S., & Norambuena, A. (2018). Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis. NEUROPHARMACOLOGY, 136, 192-195. doi:10.1016/j.neuropharm.2017.09.016

Swanson, E., Breckenridge, L., McMahon, L., Som, S., McConnell, I., & Bloom, G. S. (2017). Extracellular Tau Oligomers Induce Invasion of Endogenous Tau into the Somatodendritic Compartment and Axonal Transport Dysfunction. JOURNAL OF ALZHEIMERS DISEASE, 58(3), 803-820. doi:10.3233/JAD-170168

2016

Norambuena, A., Wallrabe, H., McMahon, L., Silva, A., Swanson, E., Khan, S. S., . . . Bloom, G. S. (2017). mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease. ALZHEIMERS & DEMENTIA, 13(2), 152-167. doi:10.1016/j.jalz.2016.08.015

Sharlow, E. R., Leimgruber, S., Lira, A., McConnell, M. J., Norambuena, A., Bloom, G. S., . . . Lazo, J. S. (2016). A Small Molecule Screen Exposes mTOR Signaling Pathway Involvement in Radiation-Induced Apoptosis. ACS CHEMICAL BIOLOGY, 11(5), 1428-1437. doi:10.1021/acschembio.5b00909

Khan, S. S., & Bloom, G. S. (2016). Tau: The Center of a Signaling Nexus in Alzheimer's Disease. FRONTIERS IN NEUROSCIENCE, 10. doi:10.3389/fnins.2016.00031

2015

Fang, X., Zhang, B., Thisse, B., Bloom, G. S., & Thisse, C. (2015). IQGAP3 is essential for cell proliferation and motility during zebrafish embryonic development. CYTOSKELETON, 72(8), 422-433. doi:10.1002/cm.21237

Wallrabe, H., Sun, Y., Fang, X., Periasamy, A., & Bloom, G. S. (2015). Three-color confocal Forster (or fluorescence) resonance energy transfer microscopy: Quantitative analysis of protein interactions in the nucleation of actin filaments in live cells. CYTOMETRY PART A, 87A(6), 580-588. doi:10.1002/cyto.a.22651

2014

Marbiah, M. M., Harvey, A., West, B. T., Louzolo, A., Banerjee, P., Alden, J., . . . Kloehn, P. -C. (2014). Identification of a gene regulatory network associated with prion replication. EMBO JOURNAL, 33(14), 1527-1547. doi:10.15252/embj.201387150

Bloom, G. S. (2014). Amyloid-β and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis. JAMA NEUROLOGY, 71(4), 505-508. doi:10.1001/jamaneurol.2013.5847

2013

Wallrabe, H., Cai, Y., Sun, Y., Periasamy, A., Luzes, R., Fang, X., . . . Bloom, G. S. (2013). IQGAP1 Interactome Analysis by In Vitro Reconstitution and Live Cell 3-Color FRET Microscopy. CYTOSKELETON, 70(12), 819-836. doi:10.1002/cm.21146

Osman, M. A., Bloom, G. S., & Tagoe, E. A. (2013). Helicobacter pylori-Induced Alteration of Epithelial Cell Signaling and Polarity: A Possible Mechanism of Gastric Carcinoma Etiology and Disparity. CYTOSKELETON, 70(7), 349-359. doi:10.1002/cm.21114

Ferrer-Acosta, Y., Rodriguez-Cruz, E. N., Orange, F., De Jesus-Cortes, H., Madera, B., Vaquer-Alicea, J., . . . Vega, I. E. (2013). EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease. JOURNAL OF NEUROCHEMISTRY, 125(6), 921-931. doi:10.1111/jnc.12155

Liu, C., Billadeau, D. D., Abdelhakim, H., Leof, E., Kaibuchi, K., Bernabeu, C., . . . Kang, N. (2013). IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver. JOURNAL OF CLINICAL INVESTIGATION, 123(3), 1138-1156. doi:10.1172/JCI63836

Seward, M. E., Swanson, E., Norambuena, A., Reimann, A., Cochran, J. N., Li, R., . . . Bloom, G. S. (2013). Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease. JOURNAL OF CELL SCIENCE, 126(5), 1278-1286. doi:10.1242/jcs.1125880

2012

Nussbaum, J. M., Seward, M. E., & Bloom, G. S. (2013). Alzheimer disease A tale of two prions. PRION, 7(1), 14-19. doi:10.4161/pri.22118

Nussbaum, J. M., Schilling, S., Cynis, H., Silva, A., Swanson, E., Wangsanut, T., . . . Bloom, G. S. (2012). Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. NATURE, 485(7400), 651-655. doi:10.1038/nature11060