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Katrien De Bock
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Prof. Dr. at ETH Zürich
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Endothelial metabolism to promote muscle revascularization and regeneration
Open Date: 2022-04-01
Close Date: 2026-03-31
Positions (1)
Katrien De Bock
ETH Zürich
1 month ago
ETH Zurich is offering a fixed-term postdoctoral-level bioinformatician position in the Laboratory of Exercise and Health , led by Prof. Dr. Katrien De Bock at the Department of Health Sciences and Technology (D-HEST). The role focuses on single-cell and spatial omics in the context of vascular biology , skeletal muscle physiology , and metabolism . The lab investigates how the muscle microvascular niche and specialized endothelial cell subpopulations interact with macrophages, pericytes, fibro-adipogenic progenitors, and other niche cells to maintain muscle homeostasis. The project combines human patient samples , mouse genetic models , single-cell and spatial transcriptomics , and CRISPR-based perturbation and cell-cell interaction tracing to understand how disrupted niche communication contributes to muscle dysfunction. The successful candidate will lead the full single-cell and spatial transcriptomics workflow and work closely with PhD students, postdocs, and Prof. De Bock. Responsibilities include scRNA-seq analysis of human and mouse skeletal muscle samples, cell-state annotation, cross-species integration, multi-omics integration with spatial transcriptomics, ATAC-seq, metabolomics and multiplex imaging, cell-cell communication analysis, metabolic modeling, pseudobulk and differential expression analysis, in silico perturbation, and the development of reproducible bioinformatics pipelines and Shiny apps. Applicants should hold a PhD in bioinformatics, computational biology, computational genomics, or a related quantitative field . Strong hands-on experience with single-cell RNA-seq analysis is essential, and experience with spatial transcriptomics is highly desirable. The role also requires strong programming skills in R and/or Python , familiarity with Bioconductor/scverse tools, version control and collaborative development platforms such as GitHub/GitLab, and experience with high-performance computing . A genuine interest in skeletal muscle physiology and/or vascular biology, strong communication skills, team spirit, and advanced English proficiency are expected. The position offers access to state-of-the-art infrastructure at ETH Zurich, dedicated computational resources, and a highly collaborative, internationally oriented research environment. The salary is competitive and aligned with ETH Zurich regulations. ETH Zurich emphasizes equality, diversity, and an inclusive working culture. Application: Submit your application online via the ETH Zurich portal with a CV, a one-page motivation/research statement, and contact details of two references. Questions about the role may be directed to Prof. Dr. Katrien De Bock at [email protected] . Applications by email or post are not accepted. Institution: ETH Zurich, Switzerland. Deadline: not specified in the posting.
1 month ago
Articles (16)
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Metastatic melanoma is either intrinsically resistant or rapidly acquires resistance to targeted therapy treatments, such as MAPK inhibitors (MAPKi). A leading cause of resistance to targeted therapy is a dynamic transition of melanoma cells from a proliferative to a highly invasive state, a phenomenon called phenotype switching. Mechanisms regulating phenotype switching represent potential targets for improving treatment of patients with melanoma. Using a drug screen targeting chromatin regulators in patient-derived three-dimensional MAPKi-resistant melanoma cell cultures, we discovered that PARP inhibitors (PARPi) restore sensitivity to MAPKis, independent of DNA damage repair pathways. Integrated transcriptomic, proteomic, and epigenomic analyses demonstrated that PARPis induce lysosomal autophagic cell death, accompanied by enhanced mitochondrial lipid metabolism that ultimately increases antigen presentation and sensitivity to T-cell cytotoxicity. Moreover, transcriptomic and epigenetic rearrangements induced by PARP inhibition reversed epithelial–mesenchymal transition-like phenotype switching, which redirected melanoma cells toward a proliferative and MAPKi-sensitive state. The combination of PARP and MAPKis synergistically induced cancer cell death both in vitro and in vivo in patient-derived xenograft models. Therefore, this study provides a scientific rationale for treating patients with melanoma with PARPis in combination with MAPKis to abrogate acquired therapy resistance. Significance: PARP inhibitors can overcome resistance to MAPK inhibitors by activating autophagic cell death and reversing phenotype switching, suggesting that this synergistic combination could help improve the prognosis of patients with melanoma.
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Collaborators (17)
Eling D. de Bruin
ETH Zürich
Andrés A Urrutia
Universidad Autónoma de Madrid
Christoffer Clemmensen
Københavns Universitet
Mark Larance
Senior Lecturer
University of Sydney
Olivier Braissant
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Jakob G Knudsen
Assistant professor
University of Copenhagen
Nicoline Resen Andersen
Københavns Universitet
Joachim Fandrey
Universitätsprofessor
Universität zu Köln Medizinische Fakultät
Ekaterina Khatchatourova
University of Bern
Peter Carmeliet
Group Leader
Aarhus University
Erik A. Richter
Københavns Universitet
Christian Stockmann
Assistant Professor for Molecular Medicine
University of Zurich
Laura Hinte
ETH Zürich
Christophe Delecluse
Full professor
KU Leuven
Michael O. Hottiger
University of Zurich
Daniel Castellano-Castillo
Assistant Professor
University of Malaga
Francisco Javier Ruiz Ojeda
Universidad de Granada
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