Research

Our group currently has three major areas of research:

• Role of protein post-translational modifications in the regulation of tissue growth

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.

• Reversible ubiquitylation and tissue invasion

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.

• Modelling tumour heterogeneity in vivo

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.

Other Activities

• Member of the European Association of Cancer Research
• Member of the British Association of Cancer Research
• Member of the Biochemical Society
• Member of the Independent Scientific Advisory Panel for the Bone Cancer Research Trust

Major Funding

• 2020-2023: BBSRC Project Grant, 'A PP2A regulatory nexus modulating Hippo signalling and growth,' £649,038
• 2017-2021- Barts Charity Large Project Grant, 'OncoChrome: A genetic system to study and exploit tumour heterogeneity,' £237,344
• 2017-2019- The Brain Tumour Charity New Ideas Award, 'A novel genetic system to study and exploit glioblastoma heterogeneity,' £74,488
• 2016-2020- Academy of Medical Sciences Springboard Award, 'The interplay between cell polarity and Hippo signalling in the regulation of tissue growth,' £99,914
• 2014-2017- Breast Cancer Now, 'Role of deubiquitylating enzymes in the regulation of breast cancer cell migration and oncogenesis,' £185,892
  
  

Recent Publications

Drice restrains Diap2-mediated inflammatory signalling and intestinal inflammation Kietz C, Mohan AK, Pollari V et al. Cell Death & Differentiation (2022) 29(10) 28-39

Casein kinase 1 family proteins promote Slimb-dependent Expanded degradation Fulford AD, Holder MV, Frith D et al. eLife 8(10) e46592

Drosophila Genetics: Analysis of Tissue Growth in Adult Tissues Fulford AD, Ribeiro PS (2019) 1893(10) 43-51

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)
https://www.ncbi.nlm.nih.gov/pubmed/29930174

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(10) 522

Prp8 regulates oncogene-induced hyperplastic growth in Drosophila Fernández-Espartero CH, Rizzo A, Fulford AD et al. Development (2018) 145(10) dev162156

Upstairs, downstairs: spatial regulation of Hippo signalling Fulford A, Tapon N, Ribeiro PS Current Opinion in Cell Biology (2018) 51(10) 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(10) 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 7(10) 10972

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

Team

Postdoctoral Researchers
Aashika Sekar

PhD Students
Alberto Rizzo, Lauren Dawson, Lucy Silcock

Research Technician
Elodie Sins

Biography

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.