Overview

We are interested in understanding the cellular and molecular mechanisms that promote cancer cell plasticity and adaptation of tumour cells in metastatic niches and under therapeutic pressure. By using dynamic analyses of the tumour microenvironment and metastatic niche in human samples and patient-derived organoids, in conjunction with single-cell omics, imaging and computational analyses, we aim to achieve a systems-level understanding of the molecular circuits and cellular crosstalk driving metastasis and therapy resistance.

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Team

Sophie Busson-Whittle

Sophie Busson-Whittle

Postdoctoral Researcher

Shenay Mehmed

Shenay Mehmed

PhD Student

Dr Zoe Mitchell

Dr Zoe Mitchell

Postdoctoral Researcher

Elise Smith profile picture

Dr Elise Smith

Postdoctoral Researcher

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Research

We employ a multidisciplinary approach that integrates computational and experimental strategies. We utilise patient samples and patient-derived organoids co-cultured with immune cells and by integrating single-cell multi-omics data, imaging and computational methods, our lab aims to dissect the cancer cell intrinsic traits and cell-cell communication networks that promote metastasis and therapy resistance.

The main areas of focus are:

Cancer Cell Plasticity

Cancer cells maintain an intrinsic plasticity that allows them to reversibly change their phenotype in response to microenvironmental signals and switch between cellular states. Single-cell studies have revealed extensive transcriptional heterogeneity along with lineage mixing and plasticity in several cancer types. In metastases, cells co-opt developmental programs and are reset to an even more primitive differentiation state, mimicking organ formation to reinitiate growth in a new location.

Using patient samples and patient-derived organoids, we are investigating the genetic vs non-genetic tumour heterogeneity and the regulatory networks underlying plasticity and invasiveness during metastasis.

Cell-cell communication

There is a growing understanding that the metastatic microenvironment is crucial in enabling the growth of disseminated cancer cells. In addition to the tumour cell intrinsic plasticity, local niche factors from stromal and immune cells influence tumour cell phenotypes and likewise, distinct cancer phenotypes shape the tumour microenvironment.

Our aim is to understand how cancer cells adapt to the metastatic niche and how in turn, immune and stromal cells support tumour cell plasticity and metastasis formation.

​Therapy Resistance

Accumulating evidence implicates phenotypic plasticity as a key mechanism towards development of resistance to both targeted and immunotherapy. We aim to understand the molecular and cellular mechanisms driving phenotypic transitions in therapy resistance. By characterising the repertoire of phenotypes present both prior to and after therapy exposure, we are investigating the phenotypic states that promote resistance and their therapeutic vulnerabilities.

Our overarching goal is to identify key targets that drive metastasis formation and therapy resistance and find potential therapeutic strategies that disrupt crucial tumour-microenvironment interactions.

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Key Publications

  • Phenotypic heterogeneity and plasticity in colorectal cancer metastasis. Cell Genomics (2025) 5(7):100881. PMID: 40393458 
  • MultiMAP: dimensionality reduction and integration of multimodal data. Genome Biology (2021) 22(1):346. PMID: 34930412
  • Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth. Cell Reports (2020) 31(7):107628. PMID: 32433953
  • CellPhoneDB: Inferring cell-cell communication from combined expression of multi-subunit receptor-ligand complexes. Nature Protocols (2020) 15(4):1484-1506. PMID: 32103204
  • Single-cell reconstruction of the early maternal-fetal interface in humans. Nature (2018) 563(7731):347-353. PMID: 30429548
See recent publications

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Major Funding

  • 2023-2029 – CRUK Career Establishment Award, “Characterising the cellular state transitions mediating colorectal cancer metastasis”,  £1,043,000
  • 2022 – Leukaemia UK, John Goldman Fellowship, “Investigating the mechanisms underlying plasticity in therapy resistance in B cell lymphomas”, £150,000
  • 2021-2024 – Chan Zuckerberg Initiative, Single-Cell Multi-omic and Spatial Cell Atlas of Pediatric Skin
  • 2020-2023 – Barts Charity, Dissecting the molecular circuits driving metastasis in melanoma

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Other Activities

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Biography

During my PhD in Computational Biology in the lab of Prof Trajanoski at the Medical University of Innsbruck, Austria, I investigated the process of clonal evolution of cancer under immunosurveillance and how the immune system shapes tumour progression.

For my postdoctoral research, I joined the Teichmann Lab (Wellcome Sanger Institute) where I co-led the development of the first human atlas of the maternal-fetal interface in early pregnancy using single cell transcriptomics. I also developed a cell-cell communication statistical framework CellPhoneDB (www.cellphonedb.org) for predicting enriched receptor-ligand pairs between the different cell types and inference of cellular communication networks. This framework allowed me to dissect the complex interplay between stromal and immune cells in the dynamic tumour microenvironment of a mouse melanoma model.

In May 2020 I started my own lab at Barts Cancer Institute, Queen Mary University of London (UK) within the Centre for Cancer Genomics and Computational Biology.

I am part of the Programme Team for the Cancer Genomics & Data Sciences MSc Programme at BCI, Queen Mary University of London. Find out more about the programme.

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Related News

Study reveals molecules enabling bowel cancer to hijack healing processes and spread

Scientists have uncovered how bowel cancer cells imitate our gut’s natural healing processes to adapt, spread and grow. The findings researchers at Barts Cancer Institute could lead to new treatment strategies aimed at preventing cancer spread.

General News   8 June 2025

Dr Mirjana Efremova awarded £1m Cancer Research UK grant to decode bowel cancer’s plastic nature

Congratulations to Dr Mirjana Efremova who has been awarded a £1m grant to use cutting-edge computational tools to study how bowel cancer adapts.

General News   14 December 2023

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