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 and tau pathology” based in the Clem Jones Centre for Ageing Dementia Research (CJCADR) within the Queensland Brain Institute (QBI) at the University of Queensland (UQ). Dr Polanco holds an MSc in Biochemistry from the National University of Colombia, and a PhD in Molecular Bioscience from the UQ. During his doctoral studies, Dr Polanco made significant contributions to unravelling the intricate mechanisms through which SOX genes are implicated in XX disorders of sex development. Subsequently, he honed his expertise during a postdoctoral fellowship at CSIRO, focusing on developing assays for the effective detection of unstable human induced pluripotent stem cells prone to tumorigenesis. In 2013, he joined the laboratory of Prof. Jürgen Götz in CJCADR. Here, Dr Polanco embarked on his pioneering work with exosomes. 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 could internalise proximal exosomal tau seeds and then re-release a fraction fused with endogenous secretory endosomes. These re-released exosomes, delivered to interconnected neurons, showcased a potential increase in pathogenicity through this trans-synaptic mode of transport (Acta Neuropathologic Communications 2018). Since 2019, Dr Polanco has successfully secured NHMRC grants and has been mentored by Prof. Götz to establish and lead an independent research team hosted in his lab.

Research Interests

  • RESEARCH TEAM: Exosomes and Tau Pathology
    Tauopathies are neurodegenerative diseases in which the microtubule-associated protein tau undergoes a process of aggregation and fibrillisation that gives rise to a pathological hallmark known as neurofibrillary tangles (NFTs). These tau lesions are prevalent in Alzheimer’s disease, frontotemporal lobar degeneration with tau, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. The current notion in the field is that Alzheimer's tau pathology could be caused by the spread of misfolded forms of tau protein, known as ‘tau seeds’, through the brain via neuronal projections. These tau seeds corrupt the conformation of soluble tau-protein in recipient neurons and are found 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. Whereas several groups focus entirely on vesicle-free tau seeds, my team is interested 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 primary 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 Neuropathologica 2021), or that the kinase Fyn is a key factor controlling the formation of NFTs in neurons (Cell Reports 2020). My team’s research has been highlighted on journal covers and commented on favourably in several research news articles.

Qualifications

  • Doctor of Philosophy, The University of Queensland

Publications

View all Publications

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

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.