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Dr Juan Polanco

Research Fellow

Queensland Brain Institute
j.polanco@uq.edu.au
+61 7 334 66326

Overview

Research Interests

  • The role of extracellular vesicles in the propagation of Alzheimer disease
    I am investigating the role of extracellular vesicles known as exosomes, in the spreading and induction of Alzheimer's pathology. In my seminal paper of 2016, we demonstrated for the first time that exosomes contained tau seeds encapsulated by their membranes, and with the ability to induce tau aggregation in recipient cells after endocytosis (Polanco et al., J Biol Chem. 2016). More recently, we obtained evidence supporting the notion that exosomes are invasive, and that exogenous exosomes, after fusion with endogenous endosomes, hijack the secretory endosomes of the cells that had internalized them, thereby achieving a longer distance of action and potentially higher pathogenicity during tau spreading in interconnected neurons (Polanco et al., Acta Neuropathol Commun 2018). At present, I am focused on addressing a critical unanswered aspect of this neuron-to-neuron propagation, which is how tau seeds inside an exosome are not only able to exit the exosomal membranes but also escape the endosome in order to access cytosolic tau and induce corrupting cycles of tau aggregation. Furthermore, I am also interested in genes and cellular processes that bring about tau aggregation, and we have demonstrated that Fyn kinase is one pivotal gene controlling the formation of neurofibrillary tangles in the neuronal soma (Briner, Götz & Polanco, Cell Rep 2020).

Qualifications

  • Doctor of Philosophy, The University of Queensland

Publications

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Grants

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Supervision

  • Understanding brain connectivity associated with proteinopathy and memory impairment in Alzheimers Disease

    Doctor Philosophy

  • Analysis of how tau spreads and forms aggregated lesions in Alzheimer¿s disease models

    Doctor Philosophy

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Available Projects

  • Unravelling How Exosomes Induce and Propagate Tau Pathology

    Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid, and tau. The tau pathology in AD usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas in a pattern that suggests that neuronal interconnectivity facilitates AD progression, characterized by increasing tau aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via extracellular vesicles such as exosomes (Polanco et al. 2018, Nat Rev Neurol). We have established that brains from mice with tau pathology produce tau seeds 'encapsulated' within exosomes (Polanco et al. 2016, J Biol Chem). Furthermore, exosomes containing tau seeds can induce tau aggregation in recipient cells (Polanco et al. 2016, J Biol Chem; Baker, Polanco and Götz 2016, J Alzheimers Dis), and exosomes spread from neuron to neuron by hijacking endosomes (Polanco et al. 2018, Acta Neuropathol Commun). Exosomes are internalised by recipient cells via endocytosis. Consequently, tau seeds must not only be able to exit the exosomal membranes, but they must also be able to escape the endosomes in order to access cytosolic tau and induce corrupting cycles of tau aggregation. We have available projects aiming to answer questions such as:

    1. How do exosomal tau seeds escape from endosomes?
    2. How to halt or reduce tau pathology by controlling exosome production or traffic?
    3. What genes are important for induction of tau aggregation?
    4. How can pivotal genes for tau aggregation be regulated?

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Publications

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Unravelling How Exosomes Induce and Propagate Tau Pathology

    Alzheimer's Disease (AD) is an irreversible and progressive dementia characterized by neurodegeneration and concomitant neuronal cell loss. The pathological progression of AD involves the aggregation and deposition of two proteins, β-amyloid, and tau. The tau pathology in AD usually starts in the hippocampus and the entorhinal cortex, and as AD progresses it spreads to other cortical areas in a pattern that suggests that neuronal interconnectivity facilitates AD progression, characterized by increasing tau aggregation and the presence of cytoplasmic neurofibrillary tangles (NFTs) in an increasing number of neurons. This suggests an active spreading mechanism, which could be via extracellular vesicles such as exosomes (Polanco et al. 2018, Nat Rev Neurol). We have established that brains from mice with tau pathology produce tau seeds 'encapsulated' within exosomes (Polanco et al. 2016, J Biol Chem). Furthermore, exosomes containing tau seeds can induce tau aggregation in recipient cells (Polanco et al. 2016, J Biol Chem; Baker, Polanco and Götz 2016, J Alzheimers Dis), and exosomes spread from neuron to neuron by hijacking endosomes (Polanco et al. 2018, Acta Neuropathol Commun). Exosomes are internalised by recipient cells via endocytosis. Consequently, tau seeds must not only be able to exit the exosomal membranes, but they must also be able to escape the endosomes in order to access cytosolic tau and induce corrupting cycles of tau aggregation. We have available projects aiming to answer questions such as:

    1. How do exosomal tau seeds escape from endosomes?
    2. How to halt or reduce tau pathology by controlling exosome production or traffic?
    3. What genes are important for induction of tau aggregation?
    4. How can pivotal genes for tau aggregation be regulated?

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Links

ResearcherID: AAE-1529-2019

ORCID: 0000-0002-3335-6332

Google Scholar ID: NEa_LVwAAAAJ

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