Research Interests: Neurodegneration, Neuroscience, Cell Biology

Research Description: Research in our laboratory is 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.

Selected Publications:

Pfister KK, Wagner MC, Stenoien DL, Brady ST, and Bloom GS. 1989. Monoclonal Antibodies to Kinesin Heavy and Light Chains Stain Vesicle-like Structures, but not Microtubules in Cultured Cells. Journal of Cell Biology 108: 1453-1463.

 https://rupress.org/jcb/article/108/4/1453/58986/Monoclonal-antibodies-to-kinesin-heavy-and-light

Hirokawa N, Pfister KK, Yorifuji H, Wagner MC, Brady ST, and Bloom GS. 1989. Submolecular Domains of Bovine Brain Kinesin Identified by Electron Microscopy and Monoclonal Antibody Decoration. Cell 56: 867-878. https://www.cell.com/fulltext/0092-8674(89)90691-0

Lippincott-Schwartz J, Cole NB, Marotta A, Conrad PA, and Bloom GS. 1995. Kinesin is the Motor for Microtubule-mediated Golgi-to-ER Membrane Traffic. Journal of Cell Biology 128: 293-306. https://rupress.org/jcb/article/128/3/293/28955/Kinesin-is-the-motor-for-microtubule-mediated.

Bashour A-M, Fullerton AT, Hart MJ, and Bloom GS. 1997. IQGAP1, a Rac- and Cdc42-binding Protein, Is An Actin-Binding Protein That Cross-Links Microfilaments. Journal of Cell Biology:  137: 1555-1566. https://rupress.org/jcb/article/137/7/1555/15555/IQGAP1-a-Rac-and-Cdc42-binding-Protein-Directly.

Sontag E, Nunbhakdi-Craig V, Lee G, Brandt R, Kamibayashi C, Kuret J, White CL III, Mumby MC, and Bloom GS. 1999. Molecular Interactions Among Phosphatase 2A, Tau, and Micro­tubules: Implications for the Regulation of Tau Phosphorylation and the Development of Tauopathies. Journal of Biological Chemistry 274: 25490-25498. https://www.jbc.org/article/S0021-9258(19)55304-2/fulltext

King ME, Kan H-M, Baas P, Erisir A, Glabe CG, and Bloom GS. 2006. Tau-Dependent Microtubule Disassembly Induced by Pre-fibrillar β-Amyloid. Journal of Cell Biology 175: 541-546. https://doi.org/10.1083/jcb.200605187.

Nussbaum JM, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe CG, Demuth H-U and Bloom GS. 2012. Prion-Like Behavior and Tau-dependent Cytotoxicity of Pyroglutamylated Amyloid-β. Nature 485: 651-655.

https://www.nature.com/articles/nature11060.

Seward ME, Swanson E, Norambuena A, Reimann A, Cochran JN, Li R, Roberson ED and Bloom GS. 2013. Amyloid-β Signals Through Tau to Drive Ectopic Neuronal Cell Cycle Re-entry in Alzheimer’s Disease. Journal of Cell Science126: 1278-1286. PMC3635465.

Bloom GS. 2014. Amyloid and Tau: the Trigger and Bullet in Alzheimer's Disease Pathogenesis JAMA Neurology 71: 505-508.

https://jamanetwork.com/journals/jamaneurology/fullarticle/1817720.

Norambuena A, Wallrabe H, McMahon L, Silva A, Swanson E, Thomas S, Baerthlein D, Kodis E, Oddo S, Mandell JW and Bloom GS. 2017. mTOR and Neuronal Cell Cycle Re-entry: How Impaired Brain Insulin Signaling Promotes Alzheimer’s Disease. Alzheimer’s & Dementia 13: 152-167. PMC5318248.

Kodis EJ, Choi S, Swanson E, Ferreira G and Bloom GS. 2018. NMDA receptor-mediated calcium influx connects amyloid-b oligomers to ectopic neuronal cell cycle re-entry in Alzheimer’s disease. Alzheimer’s & Dementia 14: 1302-1312.

https://alz-journals.onlinelibrary.wiley.com/doi/10.1016/j.jalz.2018.05.017.

Norambuena A, Wallrabe H, Cao R, Bigler Wang D, Silva A, Svindrych Z, Periasamy A, Hu S, Kim DY, Tanzi R and Bloom GS. 2018. A Novel Lysosome-to-Mitochondria Signaling Pathway Disrupted by Amyloid-β Oligomers. EMBO Journal 37: e100241. PMC6236329.

Rajbanshi B, Guruacharya A, Mandell JW and Bloom GS. 2023. Localization, induction, and cellular effects of tau phosphorylated at threonine 217. Alzheimer’s & Dementia https://doi.org/10.1002/alz.12892.