Dr Juan Polanco

Research Fellow

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

Overview

Dr Juan Carlos Polanco leads a Research team on “Exosomes, tau spreading and aggregation” in Clem Jones Centre for Ageing Dementia Research (CJCADR) within the Queensland Brain Institute (QBI) at the University of Queensland (UQ). Dr Polanco was awarded a MSc degree in Biochemistry from the National University of Colombia, and a PhD in Molecular Bioscience from the UQ. His PhD work was supervised by now Emeritus Prof. Peter Koopman, a leading developmental biologist. He stayed in the Koopman lab until 2010 where he made major contributions on how SOX genes are implicated in the XX disorders of sex development. In 2010, he started a postdoctoral fellowship in CSIRO, working on elucidating the complex biology of reprogrammed human induced pluripotent stem cells. In 2013, he joined the laboratory of Prof. Jürgen Götz in CJCADR. Here, Dr Polanco started working on exosomes, and in his ground-breaking and highly cited 2016 paper in the Journal of Biological Chemistry, he demonstrated for the first time that exosomes encapsulate tau seeds with the ability to induce tau aggregation in recipient cells. Furthermore, he also demonstrated that neurons can internalise proximal exosomal tau seeds and then re-release a fraction fused with endogenous secretory endosomes, re-released exosomes that were delivered to interconnected neurons, potentially achieving higher pathogenicity boosted by this trans-synaptic mode of transport (Acta Neuropathol Commun 2018). Since 2019, and initially supported by an NHMRC grant, Dr Polanco has been mentored by Prof Götz to lead an independent research team hosted in his lab.

Research Interests

  • RESEARCH TEAM: Exosomes, Tau Spreading and Aggregation
    Tau pathology is a defining feature of diseases collectively known as tauopathies, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration with tau (FTLD-tau), which are characterised by the presence of tau deposits known as neurofibrillary tangles (NFTs), a histological hallmark that has been closely linked to dementia. The current notion in the field is that misfolded tau seeds propagate through the brain along neuronal projections and cause tauopathy by corrupting the native conformation of soluble tau in recipient neurons. Tau seeds come in two forms: (i) ‘naked’ vesicle-free tau as in free oligomers or fibrils, and (ii) Exosomal tau seeds encapsulated within the membranes of secretory extracellular vesicles known as exosomes, which are produced by cells in late endosomes (multivesicular bodies). Whereas several groups are entirely focusing on vesicle-free tau seeds, my team has a major interest in understanding how exosomal tau seeds induce tau pathology and in which aspects these differ from vesicle-free tau seeds. My research team focuses on three major lines of investigation: (i) the role of exosomes in the spreading and induction of Alzheimer's tau pathology, (ii) elucidating mechanisms by which exosomes deliver cargoes into the cytosol, and (iii) discovering genes and elucidating cellular processes that lead to tau aggregation. We have made major contributions like demonstrating that exosomes induce endolysosomal permeabilisation as an escape route of exosomal tau seeds into the cytosol (Acta Neuropathol 2021), or that the kinase Fyn is a key factor controlling the formation of NFTs in neurons (Cell Rep 2020). The research of my team has been highlighted on journal covers and commented favourably in several research news articles.

Qualifications

  • Doctor of Philosophy, The University of Queensland

Publications

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Supervision

  • Doctor Philosophy

  • Doctor Philosophy

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Available Projects

  • Dr Polanco’s team has available projects for students, aiming at answering questions such as:

    1. Can exosomal delivery into the cytosol be controlled or modulated?
    2. Which genes regulate exosomal delivery into the cytosol?
    3. How to halt or reduce tau pathology by controlling exosome production or traffic?
    4. Which genes are important for the induction of tau aggregation?
    5. What’s the functional overlap between exosomal and vesicle-free tau seeds?

    RESEARCH APPROACH: To achieve our aims, we use skills in cell biology and cellular sensors, biochemistry, and protein engineering, high-resolution microscopy, genome-wide CRISPR screens, multi-approach bioinformatics analyses, fluorescence-activated cell sorting, the building of DNA constructs, gain-and loss-of-function assays, production of lentivirus and lentiviral work, mouse primary neuronal culture and functional assays with AD mouse models.

View all Available Projects

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.

  • Dr Polanco’s team has available projects for students, aiming at answering questions such as:

    1. Can exosomal delivery into the cytosol be controlled or modulated?
    2. Which genes regulate exosomal delivery into the cytosol?
    3. How to halt or reduce tau pathology by controlling exosome production or traffic?
    4. Which genes are important for the induction of tau aggregation?
    5. What’s the functional overlap between exosomal and vesicle-free tau seeds?

    RESEARCH APPROACH: To achieve our aims, we use skills in cell biology and cellular sensors, biochemistry, and protein engineering, high-resolution microscopy, genome-wide CRISPR screens, multi-approach bioinformatics analyses, fluorescence-activated cell sorting, the building of DNA constructs, gain-and loss-of-function assays, production of lentivirus and lentiviral work, mouse primary neuronal culture and functional assays with AD mouse models.