Dr Mirjana Efremova

MSc, PhD
Lecturer
Group Leader
Research Focus

My group focuses on understanding the cellular and molecular mechanisms that promote cancer cell plasticity and adaptation in the metastatic niche. By using dynamic analyses of the tumour microenvironment and metastatic niche in human samples and preclinical models, in conjunction with single cell-omics, spatial proteomics and sophisticated computational analyses, we aim to achieve a systems-level understanding of the molecular circuits and cellular crosstalk driving metastasis.

Key Publications

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

Major Funding
  • 2020-2023 - Barts Charity, Dissecting the molecular circuits driving metastasis in melanoma
Research

Metastasis is the major cause of cancer-related mortality, yet this complex process remains the least understood part of cancer biology. To colonise distant organs, circulating tumour cells must invade into surrounding tissues, intravasate into the circulatory system, extravasate through vascular walls into the parenchyma of distant tissues, form micrometastasis, and finally proliferate into clinically detectable metastatic lesions. During this multi-step process, 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.

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 and breast cancer. By integrating single-cell multi-omics data, imaging and computational methods, our lab aims to dissect the microenvironmental cues and cell-cell communication networks that promote metastasis. The main areas of focus are:

  1. The regulatory networks that control cancer cell plasticity and invasiveness;
  2. The role of myeloid and stromal cells in promoting tumour cell plasticity, emergence of pro-metastatic traits and metastatic seeding and their molecular crosstalk with malignant cells at pre-metastatic and metastatic niches;
  3. The mechanisms underlying the contribution of stromal cells to development of therapeutic resistance

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

Major Funding
  • 2020-2023 - Barts Charity, Dissecting the molecular circuits driving metastasis in melanoma
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.