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Research Focus

Keywords

  • Human Organoids
  • Human Embryonic Stem Cells
  • Brain Evolution
  • Clinical Conditions

  • Autism
  • Equipment & Techniques

  • Cell culture
  • Electrophysiological recording techniques
  • Microscopy
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    Dr Madeline Lancaster

    University Position
    Group Leader

    Interests

    Human brain development exhibits a number of unique characteristics, such as dramatic size expansion, unique cell types, and distinct neural stem cell behaviors. These characteristics are difficult to examine in model organisms such as mice and are often involved in neurological diseases unique to humans, like autism and schizophrenia. In an effort to better understand human brain development, we have developed a new model system, called cerebral organoids. Cerebral organoids, or mini-brains for short, are 3D tissues generated from human pluripotent stem cells that allow modelling of human brain development in vitro. Through a process of directed differentiation and a supportive 3D microenvironment, neural precursor tissue can spontaneously self-organize to form the stereotypic organization of the early human embryonic brain. Our current interests focus on neurodevelopmental disorders, as well as comparative evolutionary studies aimed at identifying factors in human brain evolution.

    Organoid axons

    Labelled axons of an organoid coloured by orientation of projection

    Key Publications

    Tissue morphology influences the temporal program of human brain organoid development.

    DOI:
    Journal: Cell Stem Cell
    Year: 2023
    Authors: Chiaradia I, Imaz-Rosshandler I, Nilges BS, Boulanger J, Pellegrini L, Das R, Kashikar ND, Lancaster MA

    Androgens increase excitatory neurogenic potential in human brain organoids

    DOI:
    Journal: Nature
    Year: 2022
    Authors: Kelava I, Chiaradia I, Pellegrini L, Kalinka AT, Lancaster MA

    An early cell shape transition drives evolutionary expansion of human forebrain

    DOI:
    Journal: Cell
    Year: 2021
    Authors: Benito-Kwiecinski S, Giandomenico SL, Sutcliffe M, Riis ES, Freire-Pritchett P, Kelava I, Wunderlich S, Martin U, Wray G, McDole K, Lancaster MA

    Human CNS barrier-forming organoids with cerebrospinal fluid production

    DOI:
    Journal: Science
    Year: 2020
    Authors: Pellegrini L, Bonfio C, Chadwick J, Begum F, Skehel M, Lancaster MA

    Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output

    DOI:
    Journal: Nature Neuroscience
    Year: 2019
    Authors: Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, Sutcliffe M, Boulanger J, Tripodi M, Derivery E, Paulsen O, Lakatos A, Lancaster MA

    Cerebral organoids model human brain development and microcephaly

    DOI:
    Journal: Nature
    Year: 2013
    Authors: Lancaster MA, Renner M, Martin C-A, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA

    Publications

    Electron cryo-tomography reveals the subcellular architecture of growing axons in human brain organoids

    DOI:
    Journal: Elife
    Year: 2021
    Authors: Hoffman PC, Giandomenico SL, Ganeva I, Wozny MR, Sutcliffe M, Lancaster MA, Kukulski W

    Generation and long-term culture of advanced cerebral organoids for studying later stages of neural development

    DOI:
    Journal: Nature Protocols
    Year: 2020
    Authors: Giandomenico SL, Sutcliffe M, Lancaster MA

    Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo

    DOI:
    Journal: Nature Neuroscience
    Year: 2020
    Authors: Chiaradia I, Lancaster MA

    SARS-CoV-2 infects the choroid plexus and disrupts the blood-CSF-barrier in human brain organoids

    DOI:
    Journal: Cell Stem Cell
    Year: 2020
    Authors: Pellegrini L, Mallery DL, Paul D, Carter AP, James LC, Lancaster MA

    Guided self-organization and cortical plate formation in human brain organoids

    DOI:
    Journal: Nature Biotechnology
    Year: 2017
    Authors: Lancaster MA, Corsini NS, Wolfinger S, Gustafson EH, Phillips AW, Burkard TR, Otani T, Livesey FJ, Knoblich JA

    Self-organized developmental patterning and differentiation in cerebral organoids

    DOI:
    Journal: EMBO Journal
    Year: 2017
    Authors: Renner M, Lancaster MA, Bian S, Choi H, Ku T, Peer A, Chung K, Knoblich JA

    Cerebral Organoids Recapitulate Epigenomic Signatures of the Human Fetal Brain

    DOI:
    Journal: Cell Reports
    Year: 2016
    Authors: Luo C, Lancaster MA, Castanon R, Nery JR, Knoblich JA, Ecker JR