Research

The interplay between the cancer cells and the cells in the tumour microenvironment (TME) is critical for the metastatic growth. Our knowledge of how the metastatic “niches” support tumour growth is still very limited, particularly at the early stage of the disease, due to the technical challenge to discriminate TME cells within the whole metastatic tissue.

Cherry-niche, a novel labelling system I developed, allows cancer cells to directly identify their surrounding cells in the metastatic microenvironment (Ombrato et al., Nature 2019). Labelled tissue cells, which represent the local metastatic niche, can be spatially discriminated, isolated from and compared to the entire tissue. Now we have the opportunity to understand how these cells change in the local niche environment.

My lab studies how different immune cell populations interact in metastasis to identify the key events required to establish a favourable “niche” to support tumour growth, in order to propose new therapeutic approaches.

To address these issues, my research aims to answer the following questions:

1. How does the immune-niche evolve in metastasis?

My lab studies how the composition of the “immune-niche” changes, both quantitatively and qualitatively during metastatic disease progression.

2. What makes a niche pro-metastatic?

Several changes occur at the distant tissue when tumour cells colonise it. However, only some of these changes will be critically required for metastatic progression.

We aim to identify the key changes in the metastatic microenvironment that support tumour growth and find potential therapeutic strategies to prevent them.

Other Activities

• Member of the British Association for Cancer Research
• Member of the European Association for Cancer Research

Major Funding

• 2022-2023 - Bowel Research UK, Inaugural Grant Award, Identify new strategies to prevent immune cells supporting liver metastasis in colorectal cancer, £50,000
• 2020-2022 - Barts Charity, Studying tumour microenvironment in metastasis.

Recent Publications

Integrated OMICs unveil the bone-marrow microenvironment in human leukemia Passaro D, Garcia-Albornoz M, Diana G et al. Cell Reports (2021) 35(7)

Generation of neighbor-labeling cells to study intercellular interactions in vivo Ombrato L, Nolan E, Passaro D et al. Nature Protocols (2021) 16(7) 872-892

Technical Advancements for Studying Immune Regulation of Disseminated Dormant Cancer Cells Ombrato L, Montagner M Frontiers in Oncology (2020) 10(1) 594514-594514

Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses Kurelac I, Iommarini L, Vatrinet R et al. Nature Communications (2019) 10(7)

Author Correction: Metastatic-niche labelling reveals parenchymal cells with stem features (Nature, (2019), 572, 7771, (603-608), 10.1038/s41586-019-1487-6) Ombrato L, Nolan E, Kurelac I et al. Nature (2019) 575(7) E8

Metastatic-niche labelling reveals parenchymal cells with stem features Ombrato L, Nolan E, Kurelac I et al. Nature (2019) 572(7) 603-608

Subclonal cooperation rewrites metastasis Ombrato L, Malanchi I Nature Cell Biology (2019) 21(7) 797-798

Mesenchymal Cancer Cell-Stroma Crosstalk Promotes Niche Activation, Epithelial Reversion, and Metastatic Colonization del Pozo Martin Y, Park D, Ramachandran A et al. Cell Reports (2015) 13(7) 2456-2469

Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1 Aulicino F, Theka I, Ombrato L et al. Stem Cell Reports (2014) 2(7) 707-720

The EMT universe: Space between cancer cell dissemination and metastasis initiation Ombrato L, Malanchi I Critical Reviews in Oncogenesis (2014) 19(7) 349-361

For additional publications, please click here

Team

PhD Students

• Aikaterini Kafka
• Christos Ermogenous

Biography

During my PhD in the lab of Prof. Maria Pia Cosma, first at the Telethon Institute for Genetics and Medicine (TIGEM, Naples, Italy) and then at the Centre for Genomic Regulation (CRG, Barcelona, Spain), I used the induced pluripotent stem cell (iPSc) technology to study the molecular mechanisms promoting somatic cell reprogramming. Next, I joined the lab of Dr. Ilaria Malanchi at The Francis Crick Institute (London, UK). During my postdoc, I developed a new labelling tool to study how the tumour microenvironment supports cancer growth in metastasis. The use of this method allowed me to identify the parenchymal tissue cells as a new component in the metastatic niche. In 2020 I started my group at the Barts Cancer Institute, Queen Mary University of London (London, UK). The theme of our work is to study the interactions between immune cells in metastasis initiation.