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 preclinical models, 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.
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
Computational methods for single-cell omics across modalities. Nature Methods (2020) 17(1):14-17. PMID: 31907463
Single-cell reconstruction of the early maternal-fetal interface in humans. Nature (2018) 563(7731):347-353. PMID: 30429548
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.
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.
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.
Single-cell sequencing reveals clonal expansions of pro-inflammatory synovial CD8 T cells expressing tissue-homing receptors in psoriatic arthritis Penkava F, Velasco-Herrera MDC, Young MD et al. Nature Communications (2020) 11(7)
P03.31 Skin dendritic cells in melanoma are key for successful checkpoint blockade therapy Prokopi N, Tripp C, Tummers B et al. Journal for ImmunoTherapy of Cancer (2020) 8(10) a35.2-a3a36
Mosquito cellular immunity at single-cell resolution Raddi G, Barletta ABF, Efremova M et al. Science (2020) 369(7) 1128-1132
Single-Cell RNA Sequencing Reveals a Dynamic Stromal Niche That Supports Tumor Growth Davidson S, Efremova M, Riedel A et al. Cell Reports (2020) 31(7)
Immunology in the Era of Single-Cell Technologies Efremova M, Vento-Tormo R, Park JE et al. Annual Review of Immunology (2020) 38(1) 727-757
CellPhoneDB: inferring cell–cell communication from combined expression of multi-subunit ligand–receptor complexes Efremova M, Vento-Tormo M, Teichmann SA et al. Nature Protocols (2020) 15(7) 1484-1506
Computational methods for single-cell omics across modalities Efremova M, Teichmann SA Nature Methods (2020) 17(1) 14-17
Resolving the fibrotic niche of human liver cirrhosis at single-cell level Ramachandran P, Dobie R, Wilson-Kanamori JR et al. Nature (2019) 575(7) 512-518
Decoding human fetal liver haematopoiesis Popescu DM, Botting RA, Stephenson E et al. Nature (2019) 574(7) 365-371
Spatiotemporal immune zonation of the human kidney Stewart BJ, Ferdinand JR, Young MD et al. Science (2019) 365(7) 1461-1466For additional publications, please click here