Dr Elena Rainero

Dr Elena RaineroLecturer
Department of Biomedical Science
The University of Sheffield
Western Bank
Sheffield
S10 2TN
United Kingdom

Room: B2-04 Florey building
Telephone: +44-(0)114 222 3696
Email: e.rainero@sheffield.ac.uk

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General

Brief career history

  • 2016- present: Lecturer, The University of Sheffield (UK)
  • 2015–2016: Research Fellow, The University of Sheffield (UK)
  • 2009–2015: Post-doctoral researcher, the Beatson Institute for Cancer Research, Glasgow (UK)

Education

  • 2010: PhD in Human Biotechnology, University of Piemonte Orientale, Novara (Italy)
  • 2006: Master Degree in Medical and Pharmaceutical Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)
  • 2004: Bachelor Degree in Biotechnology, 110/110 cum laude, University of Piemonte Orientale, Novara (Italy)

Research interests

My group is interested in understanding the role of extracellular matrix internalisation in cell migration and invasion. The extracellular matrix (ECM) is a complex network of secreted proteins that, beyond providing physical support to organs and tissues, regulates many cell functions, including proliferation, polarity, migration and oncogenic transformation. Our aims are to understand the basic molecular events regulating ECM endocytosis, as well as how ECM uptake impinges on cell migration and invasion in complex 3D environments.

In the news:


ResearchGate


Full publications

Research

Extracellular matrix internalisation in breast cancer invasion

The extracellular matrix (ECM) is a complex network of secreted proteins which not only provides tissue support, but is also involved in the control of several cell functions, including migration and oncogenic transformation. The tumour microenvironment has a pivotal role in modulating cancer initiation, progression and metastasis, while cancer cells in turn modify the composition and properties of the ECM, demonstrating a bi-directional interaction between tumour and stroma. Our research addresses cell-ECM interaction from a novel and exciting angle, investigating how the internalisation of ECM components control breast cancer cell invasion.

Fugure 1

Using a combination of different approaches, we aim at characterising how ECM internalisation controls cancer cell migration and invasion in 2 dimensions (2D), 3 dimensions (3D) and in vivo systems.

Extracellular matrix internalisation in epithelial remodelling

Most of our organs are built from epithelial cells. They are supported extracellularly by a complex network of secreted proteins collectively known as extracellular matrix (ECM). The ECM is commonly viewed as “dead space” that provides a static scaffold for organ shape and acts as an obstacle for migrating cells. However, new data strengthen the idea that there is a dynamic interplay between cells and the ECM, which actively orchestrates how cells and organs acquire their shape. Therefore, a better understanding of how cells dynamically remodel their ECM environment and how the cell-ECM interplay contributes to epithelial remodelling will shed new light on fundamental mechanisms underlying the shaping of organs.

Figure 2

The mammary gland has a tree-like structure, whereby a single monolayer of epithelial cells surrounds the lumen of the ducts. The formation of new branches, or branching morphogenesis, is controlled by hormones and growth factors, including Hepatocyte Growth Factor (HGF). Moreover, the extracellular matrix (ECM) has been shown to have a key role in this process. Our data indicate that, upon HGF stimulation of normal mammary epithelial cells (MECs), tubule formation is associated with ECM remodelling and uptake, suggesting that ECM endocytosis might contribute to branching morphogenesis.

We aim at characterising the endocytic pathway(s) responsible for ECM uptake, focusing on the integrin family of ECM receptors, and assessing the contribution of ECM uptake to branching morphogenesis in 3D environments

Funding

  • Biochemical Society – Eric Reid Fund for Methodology (2016)
  • Royal Society - Research Grant (2016)
Teaching

Undergraduate and postgraduate taught modules

Level 3:

  • BMS349 Extended Library Project
  • BMS369 Laboratory Research Project
Opportunities

Postgraduate PhD studentship

Investigating the role of the adhesion protein Tensin 3 in breast cancer invasion

The extracellular matrix (ECM) is a complex network of secreted proteins that, besides providing the scaffolding onto which tissue and organs are organised, is involved in the regulation of a variety of cell function, including survival, growth, migration and differentiation. Moreover, the interaction with the ECM has an important role in controlling tumour formation and metastasis in several cancer types, including breast cancer. Cells interact with the ECM through plasma membrane receptors, including the integrin family, which have a key role in controlling cancer cell invasion and migration. Integrins are not only found at the cell surface, but can be internalised and either be targeted for lysosomal degradation or transported back to the plasma membrane. Interestingly, the way in which integrins are trafficked intracellularly dictates how they control cell migration. My lab focuses on cell-ECM interaction from a novel and exciting angle, analysing the role of the internalisation of ECM components in promoting cancer invasiveness.

My data indicate that invasive breast cancer cells strongly up-regulate ECM uptake, compared to normal mammary epithelial cells, and the integrin-binding protein tensin-3 is required for this. Interestingly, high expression of tensin-3 correlates with poor prognosis in a cohort of breast cancer patients, supporting its role in cancer progression.

The aim of this project is the characterisation of the molecular mechanisms through which tensin-3 controls ECM internalisation and how this impinges on cancer cell invasion, analysing in particular: (1) whether tensin-3 controls ECM endocytosis through the regulation of integrin function; (2) how tensin-3 controls ECM organisation and turnover in 3D environment; (3) what is the role of tensin-3 in cancer cell migration and invasion, in both 2D and 3D settings. To mimic the physiological environment, fibroblast-generated cell-derived matrices and 3D culture systems will be used, coupled with confocal and time-lapse video microscopy.

The outcome of this project will shed new light on the role of ECM trafficking in cancer and will determine whether tensin-3 may represent a target for the development of novel anti-cancer therapeutic strategies.

To find out more about this project and how to apply see our PhD opportunities page:

PhD Opportunities

Selected publications

Journal articles