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Bloom, George

George Bloom

Primary Appointment

Biology

Contact Information

Department of Biology
Charlottesville, VA 22904-4328
Telephone: 434-243-3543
Email: gsb4g@virginia.edu
Website: http://faculty.virginia.edu/georgebloom/public_html.gsb4g/mainpage1.htm

Research Interests

Pathogenic mechanisms in Alzheimer's Disease and other neurodegenerative disorders

Research Description

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-? (A?) 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, A? 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 A? 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 A? and tau to damage neurons, to define the structures and pathological properties of various types of A? and tau oligomers, and to leverage our basic science findings to develop more effective therapeutic and diagnostic tools for AD.

Selected Publications

Rudenko L.K., Wallrabe H., Periasamy A., Siller K., Svindrych Z., Bloom G.S., Intraneuronal Tau Misfolding Induced by Extracellular Amyloid-? Oligomers, ; Journal of Alzheimer?s Disease. 17() 1125-1138 |

Norambuena A., Bloom G.S., A Novel Communication Pathway Between Lysosomes and Mitochondria Is Disrupted in Alzheimer?s Disease, ; Contact. 2() 1-4 |

Sharlow ER, Koseoglu MM, Bloom GS, Lazo JS, The Promise and Perils of Compound Discovery Screening with Inducible Pluripotent Cell-Derived Neurons., 2019; Assay and drug development technologies. () PMID: 31095406 |

Koseoglu MM, Norambuena A, Sharlow ER, Lazo JS, Bloom GS, Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer., 2018; Journal of Alzheimer's disease : JAD. 67(1) 1-11 PMID: 30452418 |

Norambuena A, Wallrabe H, Cao R, Wang DB, Silva A, Svindrych Z, Periasamy A, Hu S, Tanzi RE, Kim DY, Bloom GS, A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-? oligomers., 2018; The EMBO journal. 37(22) PMID: 30348864 | PMCID: PMC6236329

Kodis EJ, Choi S, Swanson E, Ferreira G, Bloom GS, N-methyl-D-aspartate receptor-mediated calcium influx connects amyloid-? oligomers to ectopic neuronal cell cycle reentry in Alzheimer's disease., 2018; Alzheimer's & dementia : the journal of the Alzheimer's Association. 14(10) 1302-1312 PMID: 30293574 |

Khan SS, LaCroix M, Boyle G, Sherman MA, Brown JL, Amar F, Aldaco J, Lee MK, Bloom GS, Lesn? SE, Bidirectional modulation of Alzheimer phenotype by alpha-synuclein in mice and primary neurons., 2018; Acta neuropathologica. 136(4) 589-605 PMID: 29995210 | PMCID: PMC6329667

Bloom GS, Lazo JS, Norambuena A, Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis., 2017; Neuropharmacology. 136(0) 192-195 PMID: 28965829 | PMCID: PMC5876069

Swanson E, Breckenridge L, McMahon L, Som S, McConnell I, Bloom GS, Extracellular Tau Oligomers Induce Invasion of Endogenous Tau into the Somatodendritic Compartment and Axonal Transport Dysfunction., 2017; Journal of Alzheimer's disease : JAD. 58(3) 803-820 PMID: 28482642 | PMCID: PMC5581403

Norambuena A, Wallrabe H, McMahon L, Silva A, Swanson E, Khan SS, Baerthlein D, Kodis E, Oddo S, Mandell JW, Bloom GS, mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease., 2016; Alzheimer's & dementia : the journal of the Alzheimer's Association. 13(2) 152-167 PMID: 27693185 | PMCID: PMC5318248

Sharlow ER, Leimgruber S, Lira A, McConnell MJ, Norambuena A, Bloom GS, Epperly MW, Greenberger JS, Lazo JS, A Small Molecule Screen Exposes mTOR Signaling Pathway Involvement in Radiation-Induced Apoptosis., 2016; ACS chemical biology. 11(5) 1428-37 PMID: 26938669 | PMCID: PMC5488269

Khan SS, Bloom GS, Tau: The Center of a Signaling Nexus in Alzheimer's Disease., 2016; Frontiers in neuroscience. 10() 31 PMID: 26903798 | PMCID: PMC4746348

Wallrabe H, Sun Y, Fang X, Periasamy A, Bloom GS, Three-color confocal F?rster (or fluorescence) resonance energy transfer microscopy: Quantitative analysis of protein interactions in the nucleation of actin filaments in live cells., 2015; Cytometry. Part A : the journal of the International Society for Analytical Cytology. 87(6) 580-8 PMID: 25755111 | PMCID: PMC4452401

Bloom GS, Amyloid-? and tau: the trigger and bullet in Alzheimer disease pathogenesis., 2014; JAMA neurology. 71(4) 505-8 PMID: 24493463 |

Marbiah MM, Harvey A, West BT, Louzolo A, Banerjee P, Alden J, Grigoriadis A, Hummerich H, Kan HM, Cai Y, Bloom GS, Jat P, Collinge J, Kl?hn PC, Identification of a gene regulatory network associated with prion replication., 2014; The EMBO journal. 33(14) 1527-47 PMID: 24843046 |

Seward ME, Swanson E, Norambuena A, Reimann A, Cochran JN, Li R, Roberson ED, Bloom GS, Amyloid-? signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease., 2013; Journal of cell science. 126(0) 1278-86 PMID: 23345405 | PMCID: PMC3635465

Wallrabe H, Cai Y, Sun Y, Periasamy A, Luzes R, Fang X, Kan HM, Cameron LC, Schafer DA, Bloom GS, IQGAP1 interactome analysis by in vitro reconstitution and live cell 3-color FRET microscopy., 2013; Cytoskeleton (Hoboken, N.J.). 70(12) 819-36 PMID: 24124181 | PMCID: PMC3917506

Ferrer-Acosta Y, Rodr?guez-Cruz EN, Orange F, De Jes?s-Cort?s H, Madera B, Vaquer-Alicea J, Ballester J, Guinel MJ, Bloom GS, Vega IE, EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease., 2013; Journal of neurochemistry. 125(6) 921-31 PMID: 23331044 | PMCID: PMC3676478

Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, R?nicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe CG, Demuth HU, Bloom GS, Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-?., 2012; Nature. 485(7400) 651-5 PMID: 22660329 | PMCID: PMC3367389

Nussbaum JM, Seward ME, Bloom GS, Alzheimer disease: a tale of two prions., 2012; Prion. 7(1) 14-9 PMID: 22965142 | PMCID: PMC3609044

Bamburg JR, Bloom GS, Cytoskeletal pathologies of Alzheimer disease., 2009; Cell motility and the cytoskeleton. 66(8) 635-49 PMID: 19479823 | PMCID: PMC2754410

Yan J, Yang Y, Zhang H, King C, Kan HM, Cai Y, Yuan CX, Bloom GS, Hua X, Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells., 2008; Oncogene. 28(7) 973-82 PMID: 19079338 | PMCID: PMC2645484

Bense?or LB, Kan HM, Wang N, Wallrabe H, Davidson LA, Cai Y, Schafer DA, Bloom GS, IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly., 2007; Journal of cell science. 120(0) 658-69 PMID: 17264147 |

King ME, Kan HM, Baas PW, Erisir A, Glabe CG, Bloom GS, Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid., 2006; The Journal of cell biology. 175(4) 541-6 PMID: 17101697 | PMCID: PMC2064590

Mundy DI, Machleidt T, Ying YS, Anderson RG, Bloom GS, Dual control of caveolar membrane traffic by microtubules and the actin cytoskeleton., 2002; Journal of cell science. 115(0) 4327-39 PMID: 12376564 |

Bloom GS, Goldstein LS, Cruising along microtubule highways: how membranes move through the secretory pathway., 1998; The Journal of cell biology. 140(6) 1277-80 PMID: 9508761 | PMCID: PMC2132669

Bashour AM, Fullerton AT, Hart MJ, Bloom GS, IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments., 1997; The Journal of cell biology. 137(7) 1555-66 PMID: 9199170 | PMCID: PMC2137827

Conrad PA, Smart EJ, Ying YS, Anderson RG, Bloom GS, Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps., 1995; The Journal of cell biology. 131(6) 1421-33 PMID: 8522601 | PMCID: PMC2120680

Lippincott-Schwartz J, Cole NB, Marotta A, Conrad PA, Bloom GS, Kinesin is the motor for microtubule-mediated Golgi-to-ER membrane traffic., 1995; The Journal of cell biology. 128(3) 293-306 PMID: 7844144 | PMCID: PMC2120357

Vallee RB, Bloom GS, Mechanisms of fast and slow axonal transport., 1991; Annual review of neuroscience. 14() 59-92 PMID: 1709561 |

Hirokawa N, Pfister KK, Yorifuji H, Wagner MC, Brady ST, Bloom GS, Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration., 1989; Cell. 56(5) 867-78 PMID: 2522351 |

Pfister KK, Wagner MC, Stenoien DL, Brady ST, Bloom GS, Monoclonal antibodies to kinesin heavy and light chains stain vesicle-like structures, but not microtubules, in cultured cells., 1989; The Journal of cell biology. 108(4) 1453-63 PMID: 2522455 | PMCID: PMC2115510

Bloom GS, Luca FC, Vallee RB, Microtubule-associated protein 1B: identification of a major component of the neuronal cytoskeleton., 1985; Proceedings of the National Academy of Sciences of the United States of America. 82(16) 5404-8 PMID: 3895231 | PMCID: PMC390577