Joe Abisambra, Ph.D.

Research Focus

The overall objective of our research is to investigate the molecular mechanisms underlying tau neurotoxicity, and in doing so, we seek to identify and test novel therapeutic targets.

Tauopathies

Tau is most commonly known as a microtubule stabilizing protein. The unique architecture of neurons and astrocytes makes them, arguably, the most beautiful cells in nature. This unique shape is held by a web of microtubules. These same microtubules also coordinate the traffic of cargo across long neuronal extensions. Therefore, it should not be a surprise that tubulin is one of the most abundant proteins in the brain. As such, tau has a dynamic job in binding and releasing microtubules. When this coordinated mechanism goes awry, tau adopts an abnormal conformation, which makes it pathogenic. The mechanisms leading to tau abnormalities and the reason why a change in tau’s structure becomes toxic are not known.

Diseases that share the same pathological hallmark of tau aggregation are collectively termed tauopathies. They include:

- Alzheimer’s disease
- Primary Age-Related Tauopathy
- Progressive Supranuclear Palsy
- Fronto-temporal Dementia with Parkinsonism linked to Chromosome 17
- Gangliomas and Gangliocytomas
- Argyrophilic Grain Dementia
- Corticobasal Degeneration
- Chronic Traumatic Encephalopathy
- Pick’s Disease
- Hallervorden-Spatz Disease
- Myotonic Dystrophy
- Niemann-Pick Disease, Type C
- Parkinsonism – Dementia Complex of Guam
- Post-encephalic Parkinsonism
- Some cases of Prion Disease
- Some cases of Brain Injury
- Some cases of Prion disease
- Some cases of Amyotrophic Lateral Sclerosis (ALS)

Our goal is to identify mechanisms of tau-mediated neurodegeneration in tauopathies. If successful, our results could positively impact the lives of tauopathic patients.

PubMed Publications: 

  • Castillo-Carranza, D.L.;Nilson, A.N.;Van Skike, C.E.;Jahrling, J.B.;Patel, K.;Garach, P.;Gerson, J.E.;Sengupta, U.;Abisambra, J.;Nelson, P.;Troncoso, J.;Ungvari, Z.;Galvan, V.;Kayed, R. "Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer's Disease and Related Tauopathies." Aging and disease 8, 3 (2017): 257-266. [PubMed Link] |
  • Cloyd, R.;Vandsburger, M.;Abisambra, J.F. "A new opportunity for MEMRI." Aging 9, 8 (2017): 1855-1856. [PubMed Link] | [ Full text ]
  • Fontaine, S.N.;Ingram, A.;Cloyd, R.A.;Meier, S.E.;Miller, E.;Lyons, D.;Nation, G.K.;Mechas, E.;Weiss, B.;Lanzillotta, C.;Di Domenico, F.;Schmitt, F.;Powell, D.K.;Vandsburger, M.;Abisambra, J.F. "Identification of changes in neuronal function as a consequence of aging and tauopathic neurodegeneration using a novel and sensitive magnetic resonance imaging approach." Neurobiology of aging 56, (2017): 78-86. [PubMed Link] | [ Full text ]
  • Vanderweyde, T.;Apicco, D.J.;Youmans-Kidder, K.;Ash, P.E.A.;Cook, C.;Lummertz da Rocha, E.;Jansen-West, K.;Frame, A.A.;Citro, A.;Leszyk, J.D.;Ivanov, P.;Abisambra, J.F.;Steffen, M.;Li, H.;Petrucelli, L.;Wolozin, B. "Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity." Cell reports 15, 7 (2016): 1455-1466. [PubMed Link] | [ Full text ]
  • Meier, S.;Bell, M.;Lyons, D.N.;Rodriguez-Rivera, J.;Ingram, A.;Fontaine, S.N.;Mechas, E.;Chen, J.;Wolozin, B.;Levine H, 3rd;Zhu, H.;Abisambra, J.F. "Pathological Tau Promotes Neuronal Damage by Impairing Ribosomal Function and Decreasing Protein Synthesis." The Journal of neuroscience : the official journal of the Society for Neuroscience 36, 3 (2016): 1001-7. [PubMed Link] | [ Full text ]
  • Bell, M.C.;Meier, S.E.;Ingram, A.L.;Abisambra, J.F. "PERK-opathies: An Endoplasmic Reticulum Stress Mechanism Underlying Neurodegeneration." Current Alzheimer research 13, 2 (2016): 150-63. [PubMed Link] | [ Full text ]
  • Bachstetter, A.D.;Zhou, Z.;Rowe, R.K.;Xing, B.;Goulding, D.S.;Conley, A.N.;Sompol, P.;Meier, S.;Abisambra, J.F.;Lifshitz, J.;Watterson, D.M.;Van Eldik, L.J. "MW151 Inhibited IL-1β Levels after Traumatic Brain Injury with No Effect on Microglia Physiological Responses." PloS one 11, 2 (2016): e0149451. [PubMed Link] | [ Full text ]
  • Meier, S.;Bell, M.;Lyons, D.N.;Ingram, A.;Chen, J.;Gensel, J.C.;Zhu, H.;Nelson, P.T.;Abisambra, J.F. "Identification of Novel Tau Interactions with Endoplasmic Reticulum Proteins in Alzheimer's Disease Brain." Journal of Alzheimer's disease : JAD 48, 3 (2015): 687-702. [PubMed Link] | [ Full text ]
  • Crary, J.F.;Trojanowski, J.Q.;Schneider, J.A.;Abisambra, J.F.;Abner, E.L.;Alafuzoff, I.;Arnold, S.E.;Attems, J.;Beach, T.G.;Bigio, E.H.;Cairns, N.J.;Dickson, D.W.;Gearing, M.;Grinberg, L.T.;Hof, P.R.;Hyman, B.T.;Jellinger, K.;Jicha, G.A.;Kovacs, G.G.;Knopman, D.S.;Kofler, J.;Kukull, W.A.;Mackenzie, I.R.;Masliah, E.;McKee, A.;Montine, T.J.;Murray, M.E.;Neltner, J.H.;Santa-Maria, I.;Seeley, W.W.;Serrano-Pozo, A.;Shelanski, M.L.;Stein, T.;Takao, M.;Thal, D.R.;Toledo, J.B.;Troncoso, J.C.;Vonsattel, J.P.;White CL, 3rd;Wisniewski, T.;Woltjer, R.L.;Yamada, M.;Nelson, P.T. "Primary age-related tauopathy (PART): a common pathology associated with human aging." Acta neuropathologica 128, 6 (2014): 755-66. [PubMed Link] | [ Full text ]
  • Abisambra, J.F.;Scheff, S. "Brain injury in the context of tauopathies." Journal of Alzheimer's disease : JAD 40, 3 (2014): 495-518. [PubMed Link] | [ Full text ]
  • Abisambra, J.;Jinwal, U.K.;Miyata, Y.;Rogers, J.;Blair, L.;Li, X.;Seguin, S.P.;Wang, L.;Jin, Y.;Bacon, J.;Brady, S.;Cockman, M.;Guidi, C.;Zhang, J.;Koren, J.;Young, Z.T.;Atkins, C.A.;Zhang, B.;Lawson, L.Y.;Weeber, E.J.;Brodsky, J.L.;Gestwicki, J.E.;Dickey, C.A. "Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau." Biological psychiatry 74, 5 (2013): 367-74. [PubMed Link] | [ Full text ]
  • Abisambra, J.F.;Jinwal, U.K.;Blair, L.J.;O'Leary JC, 3rd;Li, Q.;Brady, S.;Wang, L.;Guidi, C.E.;Zhang, B.;Nordhues, B.A.;Cockman, M.;Suntharalingham, A.;Li, P.;Jin, Y.;Atkins, C.A.;Dickey, C.A. "Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation." The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 22 (2013): 9498-507. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;Akoury, E.;Abisambra, J.F.;O'Leary JC, 3rd;Thompson, A.D.;Blair, L.J.;Jin, Y.;Bacon, J.;Nordhues, B.A.;Cockman, M.;Zhang, J.;Li, P.;Zhang, B.;Borysov, S.;Uversky, V.N.;Biernat, J.;Mandelkow, E.;Gestwicki, J.E.;Zweckstetter, M.;Dickey, C.A. "Imbalance of Hsp70 family variants fosters tau accumulation." FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27, 4 (2013): 1450-9. [PubMed Link] | [ Full text ]
  • Suntharalingam, A.;Abisambra, J.F.;O'Leary JC, 3rd;Koren J, 3rd;Zhang, B.;Joe, M.K.;Blair, L.J.;Hill, S.E.;Jinwal, U.K.;Cockman, M.;Duerfeldt, A.S.;Tomarev, S.;Blagg, B.S.;Lieberman, R.L.;Dickey, C.A. "Glucose-regulated protein 94 triage of mutant myocilin through endoplasmic reticulum-associated degradation subverts a more efficient autophagic clearance mechanism." The Journal of biological chemistry 287, 48 (2012): 40661-9. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;Abisambra, J.F.;Zhang, J.;Dharia, S.;O'Leary, J.C.;Patel, T.;Braswell, K.;Jani, T.;Gestwicki, J.E.;Dickey, C.A. "Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein." The Journal of biological chemistry 287, 29 (2012): 24814-20. [PubMed Link] | [ Full text ]
  • Abisambra, J.F.;Jinwal, U.K.;Suntharalingam, A.;Arulselvam, K.;Brady, S.;Cockman, M.;Jin, Y.;Zhang, B.;Dickey, C.A. "DnaJA1 antagonizes constitutive Hsp70-mediated stabilization of tau." Journal of molecular biology 421, 4-5 (2012): 653-61. [PubMed Link] | [ Full text ]
  • Trotter, J.H.;Klein, M.;Jinwal, U.K.;Abisambra, J.F.;Dickey, C.A.;Tharkur, J.;Masiulis, I.;Ding, J.;Locke, K.G.;Rickman, C.B.;Birch, D.G.;Weeber, E.J.;Herz, J. "ApoER2 function in the establishment and maintenance of retinal synaptic connectivity." The Journal of neuroscience : the official journal of the Society for Neuroscience 31, 40 (2011): 14413-23. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;Trotter, J.H.;Abisambra, J.F.;Koren J, 3rd;Lawson, L.Y.;Vestal, G.D.;O'Leary JC, 3rd;Johnson, A.G.;Jin, Y.;Jones, J.R.;Li, Q.;Weeber, E.J.;Dickey, C.A. "The Hsp90 kinase co-chaperone Cdc37 regulates tau stability and phosphorylation dynamics." The Journal of biological chemistry 286, 19 (2011): 16976-83. [PubMed Link] | [ Full text ]
  • Jones, J.R.;Lebar, M.D.;Jinwal, U.K.;Abisambra, J.F.;Koren J, 3rd;Blair, L.;O'Leary, J.C.;Davey, Z.;Trotter, J.;Johnson, A.G.;Weeber, E.;Eckman, C.B.;Baker, B.J.;Dickey, C.A. "The diarylheptanoid (+)-aR,11S-myricanol and two flavones from bayberry (Myrica cerifera) destabilize the microtubule-associated protein tau." Journal of natural products 74, 1 (2011): 38-44. [PubMed Link] | [ Full text ]
  • Abisambra, J.F.;Jinwal, U.K.;Jones, J.R.;Blair, L.J.;Koren J, 3rd;Dickey, C.A. "Exploiting the diversity of the heat-shock protein family for primary and secondary tauopathy therapeutics." Current neuropharmacology 9, 4 (2011): 623-31. [PubMed Link] |
  • Abisambra, J.F.;Blair, L.J.;Hill, S.E.;Jones, J.R.;Kraft, C.;Rogers, J.;Koren J, 3rd;Jinwal, U.K.;Lawson, L.;Johnson, A.G.;Wilcock, D.;O'Leary, J.C.;Jansen-West, K.;Muschol, M.;Golde, T.E.;Weeber, E.J.;Banko, J.;Dickey, C.A. "Phosphorylation dynamics regulate Hsp27-mediated rescue of neuronal plasticity deficits in tau transgenic mice." The Journal of neuroscience : the official journal of the Society for Neuroscience 30, 46 (2010): 15374-82. [PubMed Link] | [ Full text ]
  • O'Leary JC, 3rd;Li, Q.;Marinec, P.;Blair, L.J.;Congdon, E.E.;Johnson, A.G.;Jinwal, U.K.;Koren J, 3rd;Jones, J.R.;Kraft, C.;Peters, M.;Abisambra, J.F.;Duff, K.E.;Weeber, E.J.;Gestwicki, J.E.;Dickey, C.A. "Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden." Molecular neurodegeneration 5, (2010): 45. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;O'Leary JC, 3rd;Borysov, S.I.;Jones, J.R.;Li, Q.;Koren J, 3rd;Abisambra, J.F.;Vestal, G.D.;Lawson, L.Y.;Johnson, A.G.;Blair, L.J.;Jin, Y.;Miyata, Y.;Gestwicki, J.E.;Dickey, C.A. "Hsc70 rapidly engages tau after microtubule destabilization." The Journal of biological chemistry 285, 22 (2010): 16798-805. [PubMed Link] | [ Full text ]
  • Koren J, 3rd;Jinwal, U.K.;Jin, Y.;O'Leary, J.;Jones, J.R.;Johnson, A.G.;Blair, L.J.;Abisambra, J.F.;Chang, L.;Miyata, Y.;Cheng, A.M.;Guo, J.;Cheng, J.Q.;Gestwicki, J.E.;Dickey, C.A. "Facilitating Akt clearance via manipulation of Hsp70 activity and levels." The Journal of biological chemistry 285, 4 (2010): 2498-505. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;Koren J, 3rd;Borysov, S.I.;Schmid, A.B.;Abisambra, J.F.;Blair, L.J.;Johnson, A.G.;Jones, J.R.;Shults, C.L.;O'Leary JC, 3rd;Jin, Y.;Buchner, J.;Cox, M.B.;Dickey, C.A. "The Hsp90 cochaperone, FKBP51, increases Tau stability and polymerizes microtubules." The Journal of neuroscience : the official journal of the Society for Neuroscience 30, 2 (2010): 591-9. [PubMed Link] | [ Full text ]
  • Jinwal, U.K.;Koren, J.;O'Leary, J.C.;Jones, J.R.;Abisambra, J.F.;Dickey, C.A. "Hsp70 ATPase Modulators as Therapeutics for Alzheimer's and other Neurodegenerative Diseases." Molecular and cellular pharmacology 2, 2 (2010): 43-46. [PubMed Link] |
  • Abisambra, J.F.;Fiorelli, T.;Padmanabhan, J.;Neame, P.;Wefes, I.;Potter, H. "LDLR expression and localization are altered in mouse and human cell culture models of Alzheimer's disease." PloS one 5, 1 (2010): e8556. [PubMed Link] | [ Full text ]