Dr Laura Pellegrini; King's College London
Laura Pellegrini is a Group Leader at the Centre for Developmental Neurobiology (CDN), King’s College London. She established her lab in October 2023 after receiving the Wellcome Trust Career Development Award. Her research investigates human brain development using cerebral and choroid plexus organoids. Previously, Laura conducted her postdoctoral research at the MRC Laboratory of Molecular Biology in Cambridge, in the lab of Dr. Madeline Lancaster. There, she developed an in vitro model of the choroid plexus to study cerebrospinal fluid (CSF) secretion. This breakthrough, published in Science (Pellegrini et al., 2020a), earned her the NC3Rs International Award (2021) and was later applied to investigate SARS-CoV-2 infection in the brain (Pellegrini et al., 2020b). Her current research explores the development of the choroid plexus in humans, the secretion of disease-related biomarkers into CSF, and the mechanisms underlying barrier repair following brain injury.
The choroid plexus (ChP) is a vital tissue located in the brain ventricular system. This tissue displays a number of important functions such as forming a protective epithelial barrier and secreting the cerebrospinal fluid (CSF). To explore the development and function of the human ChP, we recently established a protocol to generate human ChP organoids using a combination of signalling molecules that are physiologically present during the stages of development of this tissue. These organoids recapitulate fundamental functions of ChP such as CSF secretion and formation of a tight epithelial barrier selectively permeable to small molecules. To characterise the development of ChP cell populations over time, we have performed a longitudinal scRNA sequencing analysis of the organoids. We found that, similarly to ChP tissue in vivo, organoids stop proliferating in vitro and develop features of a mature tissue. Next, we used this model to investigate the epithelial response to mechanical injury and we discovered that ChP epithelial cells secretes cytokines and chemokines in response to injury and undergo epithelial-to-mesenchymal transition leading to tissue repair. In conclusion, ChP organoids have been proven useful in multiple applications and represent a powerful tool to study not only developmental diseases but also tissue repair response.
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