Morscher Lab
Pediatric Cancer & Metabolism
Morscher Lab
Pediatric Cancer & Metabolism
Morscher Lab
Pediatric Cancer & Metabolism
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Research
Pediatric cancer is an urgent call to action! @MorscherLab, we aim to elucidate and target metabolic vulnerabilities in pediatric cancers and beyond.
Cancers in children are different from adults. They harbour fewer mutations and the cause of cancer development is often linked to defined genetic drivers. We focus on understanding the principles of metabolic reprogramming across different pediatric cancer types. Then we use this knowledge to reveal cancer type and patient specific metabolic vulnerabilities for novel therapies.
Curious, Passionate, Dedicated . . .
Curious, Passionate, Dedicated . . .
1 / Precision Targeting of Pediatric Cancer Metabolism
3 / Targeting Metabolic Dependencies of Translation
Whole-genome and RNA sequencing of cancers allow a profound understanding of the genetic landscape of cancers. In this project, we aim to leverage data from precision medicine trials identify patient specific genetic changes in metabolic pathways to match them to individualized treatments targeting cancer metabolism. Additionally we aim to colaboratively develop compounds for novel targets.
This work is in collaboration with at Institut Gustave Roussy (Dr. Goerger) and Université Paris-Saclay (Dr. Brenner).
2 / Targeting Folate metabolism in Pediatric Relapsed / Refractory Cancers
Folates are essential vitamine species and a target for anti-cancer therapy. We are interested why some pediatric cancers respond to folate-targeted therapies while others are completely resistant.
By elucidating resistance mechanisms on the cancer type and individual patient level we aim to find new approaches for sensitizing pediatric cancers to therapies. Disease priorities in this project are osteosarcoma and leukemia.
Across tumor types hyperactivation of the transcription factor MYC leads to poor survival in children with cancers. This protein is a master regulator of cellular metabolism and translation.
We use cell culture and in-vivo models to understand its role in pediatric cancers with a special focus on its role in reprograming translation. We use this knowledge to develop novel therapeutic approaches in a translational setting.
We have a strong transatlantic partnership with the Children’s Hospital of Philadelphia (Dr. Hogarty) and Princeton (Prof. Rabinowitz).
Technical Expertise
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Stable Isotope Tracing
A core expertise in our lab is the use of stable isotope tracing for functional evaluation of metabolism. This aims to qualitatively and quantitatively assess activity of single reactions or metabolic pathways in cancer cells.
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In vivo Stable Isotope Tracing
We develop methods at the forefont of in vivo tracing of metabolism by stable isotopes. Currently, we use mouse models to evaluate the complex inter-organ exchange of cancers in the living organism. We also use this technique to benchmark metabolism targeting drugs. Our medium-term vision is to use this technique in humans.
Multiomic Integration
We use advanced bioinformatic integration of large-scale datasets (genomics, RNA-seq, proteomics and metabolomics) to identify cancer type and patient-specific metabolic vulnerabilities in pediatric cancers. This allows for unbiased identification of new therapeutic avenues.
Ribosome Profiling
We use ribosome profiling and RiboSeq to capture ribosome activity in action. This powerful technique allows us to refine metabolic interventions targeting translation by codon-resolution profiling of the induced phenotypes.
Meet The Team
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We welcome your application!
2 Postdoctoral Fellow Positions:
- Multiomic integration with focus on genomics / ribosome profiling / proteomics
- Stable isotope tracing focus on mass spectrometry or data analysis (metabolomics / proteomics)
We encourage applications with a strong or exclusive computational / analytical background.
Students
We primarily accept students from the UZH and ETH domain and especially encourage applications with a strong basic science or computational background.
To allow for an optimal learning experience MSc projects usually require ≥9 months of investement.
Alumni
Patricia Raiser (PhD)
Caroline Eigenmann (MSc)
Caroline Frei (MSc)
Raydene Leu (MD)
Stella Gerber (MD)
Selected Publications
Integrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency
Forny, P., Bonilla, X., Lamparter, D., Shao, W., Plessl, T., Frei, C., Bingisser, A., Goetze, S., van Drogen, A., Harshman, K., Pedrioli, P. G. A., Howald, C., Poms, M., Traversi, F., Bürer, C., Cherkaoui, S., Morscher, R. J., … Froese, D.S.
Nature Metabolism, 2023
da Costa, M. E. M., Zaidi, S., Scoazec, J.-Y., Droit, R., Lim, W. C., Marchais, A., Salmon, J., Cherkaoui, S., Morscher, R.J., … Geoerger, B.
Communications Biology, 2023
Mitochondrial translation requires folate-dependent tRNA methylation
Morscher, R. J., Ducker, G. S., Li, S. HJ., Mayer, J. A., Gitai, Z., Sperl, W., Rabinowitz, J.D. Nature, 2018
Collaborators
