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Neural stem cells persist in restricted neurogenic regions of the adult brain where they continuously generate new neurons and glia. Neural stem cell behaviour is controlled by a complex interplay between transcriptional programs and extrinsic cues from the microenvironment, or niche, in which the stem cells reside.
Glioblastoma, the most common and aggressive type of adult brain tumour, also contains subpopulations of cancer cells with neural stem cell properties, termed glioma stem cells or GSCs. GSCs drive tumour growth, give rise to more differentiated tumour bulk cells and underlie resistance to therapy. Increasing evidence suggests that GSCs promote tumourigenesis by hijacking the transcriptional and signalling networks that control normal neurogenesis. Studying NSC biology and its links to GSC malignancy will therefore increase understanding of this devastating disease and lead to the development of more effective therapeutic strategies.
The main interests of my group are to understand the cellular and molecular mechanisms by which the niche controls normal NSC function and to determine how these mechanisms become deregulated in GSCs to drive tumour growth and invasion. To address these questions, we use a combination of experimental approaches, including cell biology, gene editing, proteomics, high throughput sequencing and advanced intravital microscopy in mouse models and patient-derived cells.
Current projects in the lab focus on three complementary areas (Figure 1):
The role of the niche in controlling the activation of quiescent neural stem cells
The molecular basis of oncogene and injury-induced dedifferentiation in adult glia
The microenvironmental signals that maintain GSC quiescence and drive glioblastoma invasion
Neural stem cells persist in restricted neurogenic regions of the adult brain where they continuously generate new neurons and glia. Neural stem cell behaviour is controlled by a complex interplay between transcriptional programs and extrinsic cues from the microenvironment, or niche, in which the stem cells reside.
Glioblastoma, the most common and aggressive type of adult brain tumour, also contains subpopulations of cancer cells with neural stem cell properties, termed glioma stem cells or GSCs. GSCs drive tumour growth, give rise to more differentiated tumour bulk cells and underlie resistance to therapy. Increasing evidence suggests that GSCs promote tumourigenesis by hijacking the transcriptional and signalling networks that control normal neurogenesis. Studying NSC biology and its links to GSC malignancy will therefore increase understanding of this devastating disease and lead to the development of more effective therapeutic strategies.
The main interests of my group are to understand the cellular and molecular mechanisms by which the niche controls normal NSC function and to determine how these mechanisms become deregulated in GSCs to drive tumour growth and invasion. To address these questions, we use a combination of experimental approaches, including cell biology, gene editing, proteomics, high throughput sequencing and advanced intravital microscopy in mouse models and patient-derived cells.
Current projects in the lab focus on three complementary areas (Figure 1):
The role of the niche in controlling the activation of quiescent neural stem cells
The molecular basis of oncogene and injury-induced dedifferentiation in adult glia
The microenvironmental signals that maintain GSC quiescence and drive glioblastoma invasion
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STAR protocolsno. 1 (2024): 102928-102928
CELL REPORTSno. 5 (2023): 112472-112472
引用4浏览0WOS引用
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Valeria Amodeo, Timothy Davies, Amalia Martinez-Segura,Melanie P Clements,Holly Simpson Ragdale,Andrew Bailey,Mariana Silva Dos Santos,James I MacRae,Joao Mokochinski,Holger Kramer,Claudia Garcia-Diaz,Alex P Gould,
Brooks, Lucy J., Clements, Melanie P., Burden, Jemima J.,Kocher, Daniela,Richards, Luca, Devesa, Sara Castro,Zakka, Leila,Woodberry, Megan,Ellis, Michael,Jaunmuktane, Zane,Brandner, Sebastian,Morrison, Gillian,
Nature Communicationsno. 1 (2022): 1-1
Lucy J. Brooks,Holly Simpson Ragdale,Ciaran Scott Hill,Melanie Clements,Simona Parrinello, Samantha Dickson
biorxiv(2022)
Andreas Christ Sølvsten Jørgensen,Ciaran Scott Hill,Marc Sturrock,Wenhao Tang, Saketh R. Karamched, Dunja Gorup,Mark F. Lythgoe,Simona Parrinello,Samuel Marguerat,Vahid Shahrezaei
arxiv(2022)
Nature Communicationsno. 1 (2021): 2184-2184
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