Our research group is interested in uncovering the molecular mechanisms regulating tissue growth, invasion, metastasis and tumour heterogeneity using the fruit fly Drosophila melanogaster as a genetically tractable model organism
Casein kinase 1 family proteins promote slimb-dependent expanded degradation. eLife (2019) 8:e46592. PMID: 31567070
Upstairs, downstairs: spatial regulation of Hippo signalling. Curr Opin Cell Biol (2017) 51:22-32. PMID: 29154163
The Spectrin cytoskeleton regulates the Hippo signalling pathway. EMBO J (2015) 34(7):940-54. PMID: 25712476
Crumbs promotes Expanded recognition and degradation by the SCFSlimb/β-TrCP ubiquitin ligase. Proc Natl Acad Sci USA (2014) 111(19):E1980-9. PMID: 24778256
Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signalling. Mol Cell (2010) 39(4):521-34. PMID: 20797625
Our group currently has three major areas of research:
The growth of tissues during development and adult life is the result of a fine balancing act between the proliferation, death and differentiation of cells. Understanding the mechanisms that regulate tissue growth is one of the most important unanswered questions in basic biology. We aim to characterise the molecular mechanisms regulating the newly identified Hippo signalling pathway, with an emphasis on the role of phosphorylation and ubiquitylation.
Metastasis is the migration or dissemination of cancer cells from one organ or tissue to another and is the main cause of cancer-related mortality. We are studying the role of ubiquitylation in the regulation of tissue invasion using several Drosophila models. In addition, we are collaborating with John Marshall's group to address the importance of reversible ubiquitylation for the invasive potential of breast cancer cells.
One of the main reasons why cancer therapies fail is the fact that tumours are composed of cells that carry different mutations which alter cell behaviour and potentially allow a subset of tumour cells to survive upon treatment. While studying this phenomenon in vivo is challenging, we are generating genetic tools to address tumour heterogeneity using Drosophila as a model due to the multiple genetic tools available in the fly. By combining fly genetics with microscopy imaging and mathematical modelling, we aim to characterise the basic mechanisms that underlie tumour heterogeneity and to study how specific genetic mutations alter clonal dynamics of tumour cell populations.
Casein kinase 1 family proteins promote slimb-dependent expanded degradation Fulford AD, Holder MV, Frith D et al. eLife (2019) 8(7)
Drosophila Genetics: Analysis of Tissue Growth in Adult Tissues Fulford AD, Ribeiro PS (2019) 1893(7) 43-51
Prp8 regulates oncogene-induced hyperplastic growth in drosophila Ferna¿dez-Espartero CH, Rizzo A, Fulford AD et al. Development (Cambridge) (2018) 145(7)
In vivo bioassay to test the pathogenicity of missense human AIP variants Aflorei ED, Klapholz B, Chen C et al. Journal of Medical Genetics (2018) 55(7) 522-529
A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. Foxler DE, Bridge KS, Foster JG et al. EMBO Mol Med (2018) (1)
Upstairs, downstairs: spatial regulation of Hippo signalling Fulford A, Tapon N, Ribeiro PS Current Opinion in Cell Biology (2018) 51(7) 22-32
Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins Bridge KS, Shah KM, Li Y et al. Cell Reports (2017) 20(7) 173-187
The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate caspases in their signalling roles Orme MH, Liccardi G, Moderau N et al. Nature Communications (2016) 7(7)
Patterned Anchorage to the Apical Extracellular Matrix Defines Tissue Shape in the Developing Appendages of Drosophila Ray RP, Matamoro-Vidal A, Ribeiro PS et al. Developmental Cell (2015) 34(7) 310-322
The Spectrin cytoskeleton regulates the Hippo signalling pathway Fletcher GC, Elbediwy A, Khanal I et al. EMBO Journal (2015) 34(7) 940-954For additional publications, please click here
Aashika Sekar, Damien Goutte-Gattat
Alberto Rizzo, Lauren Dawson, Lucy Silcock
I completed my undergraduate studies in the Faculty of Sciences of the University of Lisbon, where I studied Microbial Biology and Genetics. I spent my final year in the Faculty of Pharmacy studying cell death in neuronal cells.
I then entered the Gulbenkian PhD Programme in Biomedicine at the Gulbenkian Institute, which included one year of classes and laboratory rotation. This allowed me to undertake my doctoral research at the Institute of Cancer Research, London, supervised by Prof Pascal Meier, in the characterisation of the role of inhibitor of apoptosis proteins in the regulation of cell death and innate immunity.
In 2009, I joined the Dr Nicolas Tapon's laboratory at the Cancer Research UK London Research Insitute, where I studied the mechanisms regulating tissue growth, namely the Hippo tumour suppressor signaling pathway.
In August 2013, I joined Barts Cancer Institute as an Early Career Researcher in the Centre for Tumour Biology.