Prof. Dr. Sergio P. Acebrón
As a PhD student, I was fascinated by the mechanical complexity and yet biophysical adaptability of molecular machines and protein networks (Acebrón et al., JBC 2008, Acebrón et al., FEBS 2009). This mechanistic mindset has permeated my research as postdoc, project leader, and now as a group leader. I always strive to identify and characterise novel molecular mechanisms, and to understand their functional context across the biological scales of life:
If you ask any biologist how canonical WNT signalling exerts its functions during development, they will likely say via β-catenin-dependent transcription. As postdoc and project leader, I challenged this monolithic view by identifying that WNT signalling also promotes a novel post-translational programme, which we named WNT/STOP (Acebron et al., Mol Cell 2014; Acebron & Niehrs Trends Cell Biol 2016). Our discovery opened new biology to be explored beyond traditional models previously studied in WNT signalling. For example, we found that WNT signalling orchestrates a rich, post-translational programme required for mammal sperm maturation and motility in the epididymis; and uncovered a subset of infertility in man (Koch, Acebron, et al., CELL 2015). We also provided the first evidence for WNT/STOP activity in development. We identified that WNT/STOP is required for the first embryonic cleavages in transcriptionally silent Xenopus zygotes (Huang et al., PNAS 2015). Beyond basic research, our discoveries have been utilised by others to develop a novel treatment for drug-resistant acute leukaemia (Hinze et al., Cancer Cell 2019).
My lab aims at understanding how different cellular lineages integrate microenvironmental signals to successfully build and maintain a complex organism. How do cells switch between different functional programmes during development and homeostasis? How do different cellular lineages cope with a shifting microenvironment? How do embryonic lineages and stem cells ensure that the genetic blueprints required to build tissues remain unperturbed?
To address these questions, we exploit ex vivo 2D and 3D lineage specification models for human and mouse development and tissue homeostasis, including embryoids and organoids, together with genetic and acute perturbation mouse models (Giebel et al., EMBO R 2021, Bufe et al., PNAS 2021). Using genome-editing and 3D live cell imaging in different types of organoids, we characterise complex cellular phenotypes in their biological context. We utilise single-cell transcriptome & genome sequencing (sc G&T-seq) to characterise the relationship between fate and genotype across different cellular lineages. We are also generating novel genetically encoded reporter tools to monitor signal integration in high throughput analyses and in vivo. These techniques, together with state-of-the-art molecular analyses, allow us to zoom out from detailed mechanistic insights of signal transduction (interactions, modifications) to the spatial (lineage, tissue, organism) and temporal (development, homeostasis, disease, aging) characterisation of their biological relevance
CV – Sergio P. Acebrón
Professional career after scientific training
02/23 – W2 Professor of cell signalling & genome stability, Centre for Organismal Studies (COS), Heidelberg University (Germany)
07/17 – 01/23 Independent junior group leader, Cell signalling lab, Centre for Organismal Studies (COS), Heidelberg University (Germany)
2012 – 2017 Project leader, Division of Molecular Embryology. German Cancer Research Center – DKFZ (Germany). Advisor: Prof. Christof Niehrs
2009 – 2012 Postdoctoral fellow, Division of Molecular Embryology. German Cancer Research Center – DKFZ (Germany). Advisor: Prof. Christof Niehrs
Academic education
2008 PhD in Biochemistry. University of the Basque Country/Basque Centre for Biophysics (Bilbao, Spain). Project: Protein disaggregation by molecular chaperones. Highest grade by unanimity, equivalent to Summa Cum Laude. Advisor: Prof. Arturo Muga
2004 Undergraduate studies in Biochemistry and Molecular Biology, University of the Basque Country (Bilbao, Spain)
Selected awards, responsibilities, and memberships
2022 Hella Bühler Preis 2021 for “outstanding work in cancer research”
2022 Expert Review Panel of CRUK Research Career Awards
2018 – Elected member of the Heidelberg Life Sciences Research Council
2018 Visiting lecturer in Nagoya and Osaka Universities, “Foreign Researcher Program”
2017 CRUK Career Development Award [Declined]
2012 – 2015 Vice-president (2012 – 2014) and President (2014 – 2015) of the Society of Spanish Researchers in Germany (CERFA)
Acebrón Lab 