Cell State Control of Oncogenic Signalling
Group Leader:
Dr Ralitsa Madsen
Our laboratory is driven by a deceptively simple question: how can the same PIK3CA mutation cause cancer in one cellular context but not another? Inspired by rare developmental overgrowth disorders caused by post-zygotic PIK3CA mutations, we investigate how signalling context, lineage state and microenvironment shape disease outcomes. Using optimised single-cell signalling technologies and genetically engineered human iPSC-based 2D and 3D models, we systematically map the PI3K signalling “code” across differentiation hierarchies. Our long-term objective is to develop state-gating therapies: interventions that redirect pathological signalling networks away from disease-driving phenotypic states, rather than indiscriminately suppressing pathway activity.
Lab Reports
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Recent Publications
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Lab Members
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Recent Publications
2026
Levchenko A, Madsen RR. Cancer signaling beyond the genes. Curr Opin Cell Biol. 2026 Jun;100:102643.
Mruk ON, Musk AJ, Madsen RR. Protocol for PI3K inhibitor-free differentiation and maturation of human iPSC-derived arterial- and venous-like endothelial cells. STAR Protoc. 2026 Jul 30;7(3):104668.
2024
Madsen RR*, Le Marois A, Mruk O, Voliotis M, Yin S, Sufi J, Qin X, Zhao SJ, Gorczynska J, Morelli D, Davidson L, Sahai E, Korolchuk VI, Tape CJ, Vanhaesebroeck B*. Oncogenic PIK3CA corrupts growth factor signaling specificity. Molecular Systems Biology. 2024;21:126-157.
Erickson EC, You I, Perry G, Dugourd A, Donovan K, Ros S, Moss J, Ziegler R, Williamson S, Crafter C, Johannes J, Barry S, Fischer E, Gray N, Madsen RR*, Toker A*. Multi-omic profiling of breast cancer cells uncovers stress MAPK-associated sensitivity to AKT degradation. Science Signaling. 2024;17(825):eadf2670.
2023
Madsen RR*, Toker A*. PI3K signaling through a biochemical systems lens. Journal of Biological Chemistry. 2023;299(10):105224.
2021
Madsen RR*, Erickson EC, Rueda OM, Robin X, Caldas C, Toker A, Semple RK, Vanhaesebroeck B. Positive correlation between transcriptomic stemness and PI3K/AKT/mTOR signaling scores in breast cancer, and a counterintuitive relationship with PIK3CA genotype. PLOS Genetics. 2021;17:e1009876.
2020
Madsen RR*. PI3K in stemness regulation: from development to cancer. Biochemical Society Transactions. 2020;48:301-315.
Madsen RR*, Vanhaesebroeck B*. Cracking the context-specific PI3K signaling code. Science Signaling. 2020;13:eaay2940.
Postdoctoral Researcher
Aitsana Maslakova
I am a postdoctoral researcher who focuses on understanding the molecular mechanisms of phenotypic plasticity in cancer cells. Before joining the CRUK Scotland Institute, I studied the expression of human SERPINA1 gene in tumour cell lines in Moscow, Russia. My research here aims to unravel the non-genetic factors that contribute to cancer cell adaptability and resistance to therapy. In my free time, I enjoy spending time with my family and friends, exploring new places, and being in nature.
Postdoctoral Researcher
Robert Vander-Velde
I am a postdoctoral researcher in the Madsen lab who is currently working on developing iPSC derived models of primary breast angiosarcoma with the goal of studying tumour initiation. I am applying my previous experience and passion for studying tumour evolution, especially using lineage barcodes combined with single-cell RNA sequencing, to this project. In my free time I enjoy wildlife photography, reading about science and history, and indoor rock climbing.
PhD Student
Oliwia Mruk
I am an MRC-funded PhD student working on non-cell autonomous PI3K signalling regulation using iPSC-derived endothelial cell models in the context of PROS (PIK3CA-Related Overgrowth Spectrum). My research combines live-cell imaging, quantitative image analysis, and bioinformatic approaches to investigate signalling dynamics and cellular behaviour. Outside of research, I enjoy trying new food, crafts, and digital art.
PhD Student
Alexandra Musk
I am a PhD student on the Wellcome PhD programme in Molecular, Cellular and Translational Biology. My project focuses on understanding the context-dependent effects of activating PIK3CA mutations, which drive benign overgrowth disorders and are frequently implicated in a range of cancers. To investigate this, I use iPSC-derived endothelial cell models, profiling their transcriptomic and signalling landscapes via single-cell RNA sequencing and CyTOF. Outside of work, I enjoy crafting, particularly crochet and watercolours. You can see the ever-growing collection of crochet animals on my desk.
PhD Student
Sweta Swaminathan
I am a CRUK funded PhD Student working on decrypting mechanisms of PI3Kα inhibition and adaptive feedback across lineage and ligand-receptor specific constraints. To achieve this, my project uses phospho- and bulk proteomics approaches in combination with mass cytometry to investigate effects of PI3Kα inhibition using new drugs under clinical consideration in cancer and PROS. Outside of research, I love to paint and explore Scotland.