Dr Ralitsa Madsen

Cell State Control of Oncogenic Signalling

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.



Email

A woman with long brown hair and glasses smiles gently at the camera. She is wearing a navy blue collared shirt and stands against a plain white background.

A blue pencil icon tilted diagonally, drawing a horizontal line on a plain light grey background.

Biography

click here to read

Blue icon of a document with horizontal lines representing text and a folded bottom right corner, on a light grey background.

Recent Publications

click here to read

Biography

Education and qualifications

2018: PhD Metabolic and Cardiovascular Disease, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge
2014: MPhil Medical Science, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge
2013: BSc Molecular Biomedicine, University of Copenhagen

Appointments

2026–present: UKRI Future Leaders Fellow, CRUK Scotland Institute & University of Glasgow
2024–2026: UKRI Future Leaders Fellow, MRC-PPU, University of Dundee
2020–2024: Sir Henry Wellcome Fellow,
- Principal Investigator, MRC-PPU, University of Dundee (04.2024-11.2024)
- Independent Investigator, MRC-PPU, University of Dundee (05.2023-03.2024)
- Postdoctoral Researcher, UCL Cancer Institute (12.2020-04.2023)
2019–2020: Postdoctoral Fellow, UCL Cancer Institute
2018–2019: Research Fellow, Centre of Cardiovascular Science, University of Edinburgh

Other Appointments

2022–present: UK Committee on Research Integrity (UK CORI)

Awards and Prizes

2025: The Royal Society of Edinburgh Dame Anne McLaren Medal

Recent Publications

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.