Dr Paulo Ribeiro

Dr Paulo Ribeiro

BSc, MSc, PhD
Centre: Tumour Biology
Senior Lecturer
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Our research group is interested in uncovering the molecular mechanisms regulating tissue growth, invasion and metastasis using the fruit fly Drosophila melanogaster as a genetically tractable model organism.

In particular, we are focused on studying the role of post-translational modifications such as ubiquitylation in the regulation of tissue growth during normal development and during pathological conditions.

Research Details

Our group currently has three major areas of research:

1 – Role of ubiquitylation 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 ubiquitylation.

2 – 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, among others, the border cell system in the developing Drosophila oocyte as a model for collective cell migration. 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.

3 – 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.

Profile

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.

Funding

• 2017-2020 - Barts and The London Charity Large Project Grant: “OncoChrome: A genetic system to study and exploit tumour heterogeneity” - £197,344
• 2017-2018 - Brain Tumour Charity New Ideas Awards: “A novel genetic system to study and exploit glioblastoma heterogeneity” - £74,488
• 2016-2018 - 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 Campaign Project Grant: "Role of deubiquitylating enzymes in the regulation of breast cancer cell migration and oncogenesis" - £185,000

Key Publications

Fulford A, Tapon N, Ribeiro PS. Upstairs, downstairs: spatial regulation of Hippo signalling. Curr Opin Cell Biol (2017) Nov 17; 51:22-32. PMID: 29154163

Orme M, Liccardi G, Moderau N, Feltham R, Wicky-John S, Tenev T, Aram L, Wilson R, Bianchi K, Robertson D, Tare MM, Wepf A, Williams D, Bergmann A, Gstaiger M, Arama E, Ribeiro PS, Meier P. The unconventional myosin CRINKLED and its mammalian orthologue MYO7A regulate initiator caspases in their signalling roles. Nat Commun (2016) Mar 10; 7:10972. PMID: 26960254

Fletcher GC*, Elbediwy A*, Khanal I*, Ribeiro PS*, Tapon N, Thompson BJ. The Spectrin cytoskeleton regulates the Hippo signalling pathway. EMBO J (2015) 34(7):940-54. * - equal author contribution. PMID: 25712476

Ribeiro PS, Holder MV, Frith D, Snijders AP, Tapon N. Crumbs promotes Expanded recognition and degradation by the SCFSlimb/β-TrCP ubiquitin ligase. Proc Natl Acad Sci USA 2014 May; 111(19):E1980-9. PMID: 24778256

Ribeiro PS*, Wepf A*, Josue F*, Wehr MC, Rinner O, Kelly G, Tapon N, Gstaiger M. Combined functional genomic and proteomic approaches identify a PP2A complex as a negative regulator of Hippo signalling. Mol Cell 2010 Aug; 39(4):521-34. * - equal author contribution. PMID: 20797625


Further Publications

For Additional Publications, click here.


Our research group is interested in uncovering the molecular mechanisms regulating tissue growth, invasion and metastasis using the fruit fly Drosophila melanogaster as a genetically tractable model organism.

In particular, we are focused on studying the role of post-translational modifications such as ubiquitylation in the regulation of tissue growth during normal development and during pathological conditions.

External Activities

  • Member of the European Association of Cancer Research
  • Member of the British Association of Cancer Research
  • Member of the Biochemical Society

See other researchers working on:

Breast Cell Signalling Genetics Metastasis and Invasion
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