Ralitsa R. Madsen

I obtained my undergraduate degree (B.Sc.) in Molecular Biomedicine from the University of Copenhagen (2010-2013), after which I moved to Cambridge, UK to complete an MPhil in Medical Science, under the supervision of Prof Susan Ozanne and Prof Kenneth Siddle at the Metabolic Research Laboratories - Institute of Metabolic Science (Wellcome Trust-MRC). My MPhil research focused on the contribution of microRNAs to the development of insulin resistance as a result of a suboptimal nutritional environment in utero. I subsequently completed a four-year Wellcome Trust PhD Programme in Metabolic and Cardiovascular Disease (2014-2018), with an initial MRes year. During my PhD with Prof Robert Semple, I engineered the first human induced pluripotent stem cell models with endogenous expression of either one or two copies of the cancer-associated PIK3CA-H1047R variant. Our initial aim was to study the potential mechanisms whereby this mutation causes rare, developmental overgrowth disorders known as PIK3CA-related overgrowth spectrum (PROS). In the course of this work, we discovered allele dose-dependent effects of genetic PIK3CA activation, suggesting that there are quantitative PI3K signalling thresholds that may determine the pathophysiological consequences of PIK3CA mutations in human diseases, most notably cancer. After a short postdoc in the Semple Lab upon its move to the University of Edinburgh (2018-2019), I joined the laboratory of Prof Bart Vanhaesebroeck at University College London. From 2019-2020, I worked on developing highly robust, cell-based quantitative assays for studies of small molecule-mediated PIK3CA activation. In a separate project, I also used computational approaches to identify evidence for dose-dependent PI3K signalling activation in human breast cancers with one or multiple copies of activating PIK3CA mutations. In December 2020, I was awarded a Sir Henry Wellcome Postdoctoral Fellowship to study the systems biology of PI3K-dependent phenotypic plasticity, with primary basis at UCL Cancer Institute and the CellSig laboratory of Prof Bart Vanhaesebroeck. I developed novel cellular systems for quantitative, single-cell PI3K signalling studies and applied them to studies of growth factor-specific PI3K signalling fingerprints in different genetic contexts. During this time, I also benefited from a collaboration with Prof Alex Toker at Beth Israel Deaconess Medical Center, in which we focused on the discovery of novel aspects of AKT biology through a multiomic characterisation of a second-generation AKT degrader. In May 2023, I transferred my fellowship to the MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee, to become an Independent Investigator. Outside the lab, I am involved in national and international efforts to promote Open Research. On 1 May 2022, I was appointed to serve on the inaugural UK Committee on Research Integrity for an initial term of 3 years, representing the voice of Early Career Researchers in efforts to champion research integrity and a positive research culture across the UK.