Research

We employ a multidisciplinary approach that integrates computational and experimental strategies. Through collaborations with clinicians and researchers, we have access to patient samples and preclinical models, focusing on melanoma, pancreatic and colorectal cancer. 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 multi-omics single-cell and bulk data, 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.

Visit my laboratory website here.

Other Activities

• Part of the Programme Team for the Cancer Genomics & Data Sciences MSc Programme at BCI, Queen Mary University of London.

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

Recent Publications

scMoMaT jointly performs single cell mosaic integration and multi-modal bio-marker detection Zhang Z, Sun H, Mariappan R et al. Nature Communications (2023) 14(7)

1009 – GENETIC IDENTIFICATION OF THE CELLULAR INTERACTOME THAT SUPPORTS T-CELL DEVELOPMENT IN THE THYMUS Ganuza M, Sanchez-Lanzas R, Jimenez-Pompa A et al. Experimental Hematology (2023) 124(10) s24

GENETIC IDENTIFICATION OF THE CELLULAR INTERACTOME THAT SUPPORTS T-CELL DEVELOPMENT IN THE THYMUS Ganuza M, Sanchez-Lanzas R, Jimenez-Pompa A et al. EXPERIMENTAL HEMATOLOGY (2023) 124(11) S24-S24
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:001057881700006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

Longitudinal Single Cell Analyses Reveal the Co-Evolutionary Dynamics of the Tumor and Microenvironment Accompanying Follicular Lymphoma Transformation Perrett M, Pickard L, Kumar E et al. Blood (2022) 140(10) 748-749

A Roadmap for the Human Oral and Craniofacial Cell Atlas Caetano AJ, Sequeira I, Byrd KM et al. Journal of Dental Research (2022) 101(7) 1274-1288

Spatially resolved poised immunity in human skin Fletcher J, Vegh P, Reynolds G et al. BRITISH JOURNAL OF DERMATOLOGY (2022) 187(11) E7-E8
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000820115600063&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a

MultiMAP: dimensionality reduction and integration of multimodal data Jain MS, Polanski K, Conde CD et al. Genome Biology (2021) 22(7)

Blood and immune development in human fetal bone marrow and Down syndrome Jardine L, Webb S, Goh I et al. Nature (2021) 598(7) 327-331

Mapping Rora expression in resting and activated CD4+ T cells Haim-Vilmovsky L, Henriksson J, Walker JA et al. PLoS ONE (2021) 16(7)

Developmental cell programs are co-opted in inflammatory skin disease Reynolds G, Vegh P, Fletcher J et al. Science (2021) 371(7)

For additional publications, please click here

Team

Postdoctoral Researchers

• Dr Samuel Ogden

PhD Students

• Nasrine Metic

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.