Morscher Lab
Pediatric Cancer & Metabolism
Science starts with Wonder
Metabolism is the process by which food is converted into energy, building blocks, or waste products. Our laboratory is dedicated to understanding metabolism in human health and disease. Using the latest technologies, we study metabolic programs from whole organisms to individual cells. Working at the intersection of basic science and clinical research allows us to translate molecular insights into the clinic, with a focus on children with cancer. We envision that a functional understanding of metabolism - personalized for each child or adult - will enable the development of more effective and better tolerated treatments.
Science starts with Wonder
Metabolism is the process by which food is converted into energy, building blocks, or waste products. Our laboratory is dedicated to understanding metabolism in human health and disease. Using the latest technologies, we study metabolic programs from whole organisms to individual cells. Working at the intersection of basic science and clinical research allows us to translate molecular insights into the clinic, with a focus on children with cancer. We envision that a functional understanding of metabolism - personalized for each child or adult - will enable the development of more effective and better tolerated treatments.
3241
genes of approximately 36'000 human genes are known to be involved in metabolism. They give rise to enzymes and transporters, which produce and move metabolites.
222'860
endogenous metabolites are known in humans (HMDB). These are generated through tens of thousands of chemical reactions organized in interconnected pathways.
19'500
genes are estimated to code for proteins. This genetic code instructs cells how to assemble 20 different amino acids into the full range of human proteins.
70'000
different proteins result from translating the genetic code. These proteins are further modified to an estimated amount of several million proteoforms.
Subcellular Metabolism
We study the regulation of protein translation in cancers. Our core interest lies in the intersection of cellular metabolic state and translation beyond classic signaling. We investigate changes in translation dynamics and related phenotypes based on epitranscriptomic modifications and ionic interactions (polyamines). Current projects focus on differential regulation of proliferation and differentiation in stem cells and childhood cancers.
Single Cell Metabolism
We develop technology investigating cellular heterogeneity in metabolism by metabolic flux profiles at single cell level. Elucidating metabolic networks at baseline and under treatment pressure informs treatments targeting defined sub-populations in cancer. Projects focus on technology development for tracing and the intersection with drug response.
Whole-Body Metabolism
We are interested in a personalized understanding of metabolism in physiology and disease. We study the metabolic crosstalk of healthy organs and its reprogramming in response to mutations or cancer. For treatments, we explore how targeted changes in whole-body metabolic state by diets or enzymes impact tumor growth and therapy response. Projects include polyamines, amino acids and one-carbon metabolism.
Research
Subcellular Metabolism
We study the regulation of protein translation in cancers. Our core interest lies in the intersection of cellular metabolic state and translation beyond classic signaling. We investigate changes in translation dynamics and related phenotypes based on epitranscriptomic modifications and ionic interactions (polyamines). Current projects focus on differential regulation of proliferation and differentiation in stem cells and childhood cancers.
Single Cell Metabolism
We develop technology investigating cellular heterogeneity in metabolism by metabolic flux profiles at single cell level. Elucidating metabolic networks at baseline and under treatment pressure informs treatments targeting defined sub-populations in cancer. Projects focus on technology development for tracing and the intersection with drug response.
Whole-Body Metabolism
We are interested in a personalized understanding of metabolism in physiology and disease. We study the metabolic crosstalk of healthy organs and its reprogramming in response to mutations or cancer. For treatments, we explore how targeted changes in whole-body metabolic state by diets or enzymes impact tumor growth and therapy response. Projects include polyamines, amino acids and one-carbon metabolism.
Research
Understanding Translation
Translation regulation in health and disease is complex. We use a combination of high resolution ribosome profiling to track translation at codon-level resolution, tRNA sequencing and RNA mass spectrometry to study how the epitranscriptomic landscape shapes gene expression. Functional studies integrate arrayed metabolite depletion assays, drug treatments and genetic models to reveal how how metabolism shapes translation dynamics.
Multi-Omics Integration
Analyzing the molecular composition of cellular states at high resolution has become an integral part of clinical diagnostics. We aim to leverage multilayered advanced molecular profiling to enhance our understanding of metabolism in complex biological samples, such as patient tumors. The deeper understanding of correlations from static biomarkers to metabolic function will allow the prioritization of treatments targeting metabolism.
Stable Isotope Tracing
In vivo stable isotope tracing enables a quantitative assessment of metabolic fluxes in living organisms. We leverage this non-toxic and non-radioactive technique from basic science projects to application directly in patients. By revealing metabolic operation of targetable pathways in organs and tumors we envision to inform functional biomarkers for personalized treatment decisions.
_edited_edited.jpg)
_edited.jpg)
_edited_edited.jpg)
Technical Expertise
Understanding Translation
Translation regulation in health and disease is complex. We use a combination of high resolution ribosome profiling to track translation at codon-level resolution, tRNA sequencing and RNA mass spectrometry to study how the epitranscriptomic landscape shapes gene expression. Functional studies integrate arrayed metabolite depletion assays, drug treatments and genetic models to reveal how how metabolism shapes translation dynamics.
Multi-Omics Integration
Analyzing the molecular composition of cellular states at high resolution has become an integral part of clinical diagnostics. We aim to leverage multilayered advanced molecular profiling to enhance our understanding of metabolism in complex biological samples, such as patient tumors. The deeper understanding of correlations from static biomarkers to metabolic function will allow the prioritization of treatments targeting metabolism.
Stable Isotope Tracing
In vivo stable isotope tracing enables a quantitative assessment of metabolic fluxes in living organisms. We leverage this non-toxic and non-radioactive technique from basic science projects to application directly in patients. By revealing metabolic operation of targetable pathways in organs and tumors we envision to inform functional biomarkers for personalized treatment decisions.
Technical Expertise
Selected Publications
To address the urgent need for new therapies in recurrent and refractory pediatric cancers, this study established 131 patient-derived xenograft (PDX) models through the MAPPYACTS trial. These models represent diverse tumor types that closely mirror the histological and molecular profiles of the original patient tumors. Comprehensive genomic and metabolic characterization was performed, and 90 models were shared with the IMI2 ITCC-P4 platform. This PDX biobank is a valuable resource for advancing basic and translational research.
Communications Biology, 2023
Muscle stem cell (MuSC) fate is shaped by metabolism, but key mechanisms remain unclear. We show that glutamine-driven anaplerosis declines during MuSC differentiation, along with reduced expression of the mitochondrial enzyme GLUD1. Loss of Glud1 accelerates differentiation and impairs self-renewal by causing mitochondrial glutamate accumulation and inhibiting the malate-aspartate shuttle (MAS), disrupting NAD+/NADH balance. Restoring MAS or NAD+/NADH balance rescues normal myogenesis. Thus, GLUD1 acts as a compartment-specific metabolic brake on MuSC differentiation.
Developmental Cell, 2024
The growth of neuroblastoma, a deadly childhood cancer, is fueled by metabolites like polyamines. Here we show that combining the polyamine synthesis inhibitor difluoromethylornithine (DFMO) with arginine and proline depletion enhances survival in the TH-MYCN mouse model. This combination depletes polyamines, stalls ribosomes specifically at adenosine-ending codons, and impairs translation of cell cycle genes while favoring differentiation. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.
BiorXiv, 2023
To address the urgent need for new therapies in recurrent and refractory pediatric cancers, this study established 131 patient-derived xenograft (PDX) models through the MAPPYACTS trial. These models represent diverse tumor types that closely mirror the histological and molecular profiles of the original patient tumors. Comprehensive genomic and metabolic characterization was performed, and 90 models were shared with the IMI2 ITCC-P4 platform. This PDX biobank is a valuable resource for advancing basic and translational research.
Communications Biology, 2023
Muscle stem cell (MuSC) fate is shaped by metabolism, but key mechanisms remain unclear. We show that glutamine-driven anaplerosis declines during MuSC differentiation, along with reduced expression of the mitochondrial enzyme GLUD1. Loss of Glud1 accelerates differentiation and impairs self-renewal by causing mitochondrial glutamate accumulation and inhibiting the malate-aspartate shuttle (MAS), disrupting NAD+/NADH balance. Restoring MAS or NAD+/NADH balance rescues normal myogenesis. Thus, GLUD1 acts as a compartment-specific metabolic brake on MuSC differentiation.
Developmental Cell, 2024
The growth of neuroblastoma, a deadly childhood cancer, is fueled by metabolites like polyamines. Here we show that combining the polyamine synthesis inhibitor difluoromethylornithine (DFMO) with arginine and proline depletion enhances survival in the TH-MYCN mouse model. This combination depletes polyamines, stalls ribosomes specifically at adenosine-ending codons, and impairs translation of cell cycle genes while favoring differentiation. These results suggest that the genes of specific cellular programs have evolved hallmark codon usage preferences that enable coherent translational rewiring in response to metabolic stresses, and that this process can be targeted to activate differentiation of pediatric cancers.
BiorXiv, 2023
Selected Publications
The Team
Raphael Morscher
Group Leader
Raphael J. Morscher is passionate about fundamental principles of metabolism and their application for impact in humans. He is also a practicing pediatric oncologist at the University Children’s Hospital Zurich.
Raphael completed his academic training at the Paracelsus Medical University in Salzburg (MD-PhD) with highest honors, “sub auspiciis praesidentis rei publicae”, awarded by the Austrian Government. During his graduate studies he focused on inborn errors of metabolism and cancer metabolism in neuroblastoma. He then moved to Princeton University for a postdoctoral fellowship, developing in vivo stable isotope tracing techniques with Joshua Rabinowitz. It was also during this time, his work on folate-dependent tRNA modifications sparked his interest in understanding how metabolism regulates protein translation at the tRNA /mRNA intersection. Among other accolades, he received the INSERM Chair in Pediatric Oncology and the Prof. Dr. Max Cloëtta award in 2025.
The Team
Raphael Morscher
Group Leader
Raphael J. Morscher is passionate about fundamental principles of metabolism and their application for impact in humans. He is also a practicing pediatric oncologist at the University Children’s Hospital Zurich.
Raphael completed his academic training at the Paracelsus Medical University in Salzburg (MD-PhD) with highest honors, “sub auspiciis praesidentis rei publicae”, awarded by the Austrian Government. During his graduate studies he focused on inborn errors of metabolism and cancer metabolism in neuroblastoma. He then moved to Princeton University for a postdoctoral fellowship, developing in vivo stable isotope tracing techniques with Joshua Rabinowitz. It was also during this time, his work on folate-dependent tRNA modifications sparked his interest in understanding how metabolism regulates protein translation at the tRNA /mRNA intersection. Among other accolades, he received the INSERM Chair in Pediatric Oncology and the Prof. Dr. Max Cloëtta award in 2025.
Sandra Kienast is an RNA specialist with a strong background in RNA MS. After earning her MSc from ETH Zurich, she completed her PhD at the Max Planck Institute and the University of Bern, focusing on how tRNA modifications influence cellular homeostasis. Currently she is exploring the link between metabolism, tRNA biology, and protein biosynthesis.
Nazek Noureddine is a biochemist specialized in lipid biology and immunology. She completed her PhD at the University of Zurich, where she studied anti-inflammatory mechanisms of omega-3 fatty acids. She currently investigates how dietary lipids modulate immune response and tumor progression in childhood cancers.
Chengkang Li earned his PhD at the University of Copenhagen, where he studied protein modifications. He then developed an RNA modification detection method using LC-MS at Goethe University. Now at the Morscher Lab, he is expanding his capabilities with multi-omics, while maintaining a core focus on LC-MS-based epitranscriptomics.
Fiona Farnhammer earned her MSc in Molecular Biology from the University of Vienna, where she studied WNT signaling in cancer. She then completed a one-year internship at the University of Toronto, working on the single-cell heterogeneity of the brain vasculature. Now pursuing a PhD, she focuses on therapy resistance mechanisms in osteosarcoma.
Simona Ulrich is a physician-scientist in training. After studying medicine at Charles University in Prague, and working as a pediatric oncologist, she began her MD-PhD focusing on metabolic vulnerabilities in childhood cancers. Currently she is combining drug response profiling with metabolic interventions and integrating this data with various other omics.
Yuan Yuan earned her BSc in Veterinary Medicine from the Sichuan Agricultural University and her MSc from the China Agricultural University. With strong expertise in animal models and molecular biology, she currently investigates the anti-tumor mechanisms triggered by polyamine depletion.
Caroline Mussak obtained her MSc in Immunology at the University of Zurich. For her thesis she investigated the interplay between innate lymphoid cells and myeloid cells in steady state. She joined the Morscher lab in 2023 as a research associate to establish and conduct in vivo stable isotope tracing.
Onyeka Iroh is a medical student at the University of Zurich. For her master’s thesis, she analyzed treatment protocols for childhood cancers, focusing on differences in treatment groups, tumor types, and therapies. She is now developing a database of pediatric oncology chemotherapies and is passionate about translating research into evidence-based clinical practice.
Vinzent Lindemann earned his BSc in Medicine from the University of Zurich. He is currently enrolled in the MD-PhD program and studies the effect of dietary lipids on immune modulation and tumor growth. Driven by an enthusiasm for fundamental science principles he works on disentangling the crosstalk between cancer cells and immune cells.
Clarissa Bisang earned her BSc in Biomedicine at the University of Zurich. During her studies, she developed a strong interest in the molecular mechanisms of cancers and their clinical relevance. Now pursuing her MSc, she is currently investigating amino acid metabolism dependencies in pediatric cancers.
Children battling cancer are true heroes. After overcoming their disease, each child leaves a colored handprint on a wall in our clinic. This symbol of joy and hope inspires other children and their families during treatment. Our logo calls for support of children in this vulnerable time, and symbolizes the mark each child leaves on all those who accompanies them on their journey.
Our Logo
Our Logo
Children battling cancer are true heroes. After overcoming their disease, each child leaves a colored handprint on a wall in our clinic. This symbol of joy and hope inspires other children and their families during treatment. Our logo calls for support of children in this vulnerable time, and symbolizes the mark each child leaves on all those who accompanies them on their journey.
ITTC
In vivo stable isotope tracing enables a quantitative assessment of metabolic fluxes in living organisms. We leverage this non-toxic and non-radioactive technique from basic science projects to application directly in patients. By revealing metabolic operation of targetable pathways in organs and tumors we envision to inform functional biomarkers for personalized treatment decisions.
NCCR
In vivo stable isotope tracing enables a quantitative assessment of metabolic fluxes in living organisms. We leverage this non-toxic and non-radioactive technique from basic science projects to application directly in patients. By revealing metabolic operation of targetable pathways in organs and tumors we envision to inform functional biomarkers for personalized treatment decisions.
Translacore
In vivo stable isotope tracing enables a quantitative assessment of metabolic fluxes in living organisms. We leverage this non-toxic and non-radioactive technique from basic science projects to application directly in patients. By revealing metabolic operation of targetable pathways in organs and tumors we envision to inform functional biomarkers for personalized treatment decisions.
Networks
Congratulations to S. Cherkaoui and our collaborators on their preprint, "Reprogramming neuroblastoma by diet-enhanced polyamine depletion". They show that a polyamine-depleting diet combined with DFMO disrupts tumor metabolism, stalls translation and drives neuroblastoma differentiation. Unexpectedly, they also uncovered a previously unknown link between metabolic stress and translational rewiring.
On the 2.11.2024 our lab moved to the new, state-of-the-art campus in Lengg, together with the University Children's Hospital Zurich. We are now located on the E-floor of the research tower. This move marks a major milestone for us, providing access to cutting-edge facilities and placing us at the heart of a vibrant medical and academic community.
Congratulations to G. Fitzgerald, S. Cherkaoui and our collaborators on their recent publication in Developmental Cell, titled "GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels". In this work they reveal a previously unrecognized connection between mitochondrial metabolism and the regulation of muscle stem cell fate.
News
Congratulations to G. Fitzgerald, S. Cherkaoui and our collaborators on their recent publication in Developmental Cell, titled "GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels". In this work they reveal a previously unrecognized connection between mitochondrial metabolism and the regulation of muscle stem cell fate.
On the 2.11.2024 our lab moved to the new, state-of-the-art campus in Lengg, together with the University Children's Hospital Zurich. We are now located on the E-floor of the research tower. This move marks a major milestone for us, providing access to cutting-edge facilities and placing us at the heart of a vibrant medical and academic community.
Congratulations to S. Cherkaoui and our collaborators on their preprint, "Reprogramming neuroblastoma by diet-enhanced polyamine depletion". They show that a polyamine-depleting diet combined with DFMO disrupts tumor metabolism, stalls translation and drives neuroblastoma differentiation. Unexpectedly, they also uncovered a previously unknown link between metabolic stress and translational rewiring.
News
Education
Students
We are always looking for students from the UZH and ETH domain and encourage applications with a strong basic science or computational background. To allow for an optimal learning experience MSc projects usually require ≥9 months of investment. Please send us your CV and 2 references in the application.
Alumni
Sarah Cherkaoui (Postdoc)
Patricia Raiser (MD-PhD)
Caroline Eigenmann (MSc)
Raydene Leu (MD)
Shreshtha Behera (MSc)
Gillian Fitzgerald (Postdoc)
Caroline Frei (MSc)
Stella Gerber (MD)
Michelle Shao (MD)
Angela Lässig (MSc)
Matteo Hille (BSc)
Education
Students
We are always looking for students from the UZH and ETH domain and encourage applications with a strong basic science or computational background. To allow for an optimal learning experience MSc projects usually require ≥9 months of investment. Please send us your CV and 2 references in the application.
Alumni
Sarah Cherkaoui (Postdoc)
Patricia Raiser (MD-PhD)
Caroline Eigenmann (MSc)
Raydene Leu (MD)
Shreshtha Behera (MSc)
Gillian Fitzgerald (Postdoc)
Caroline Frei (MSc)
Stella Gerber (MD)
Michelle Shao (MD)
Angela Lässig (MSc)
Matteo Hille (BSc)
Support
Selected Collaborators
Collaborative projects are at the heart of our research. We partner with leading hospitals and research institutions worldwide to advance the understanding of cancer metabolism and develop innovative treatment approaches.
Birgit Geoerger (Gustave Roussy)
Katrien De Bock (ETH Zürich)
Jean-Pierre Bourquin (University Children's Hospital Zürich)
Daniel Herranz (Rutgers Cancer Institute)
Michael Hogarty (Children's Hospital of Philadelphia)
Matthias Baumgartner (University Children's Hospital Zürich)
Sean Froese (University Children's Hospital Zürich)
Joshua Rabinowitz (Princeton University)
Selected Funding Sources
Our work is supported by governmental funding agencies, foundations and private donations. If you want to support our mission please contact us or donate here.
Our work is supported by governmental funding agencies, foundations and private donations. If you want to support our mission please contact us or donate here.
Selected Funding Sources
Birgit Geoerger (Gustave Roussy)
Katrien De Bock (ETH Zürich)
Jean-Pierre Bourquin (University Children's Hospital Zürich)
Daniel Herranz (Rutgers Cancer Institute)
Michael Hogarty (Children's Hospital of Philadelphia)
Matthias Baumgartner (University Children's Hospital Zürich)
Sean Froese (University Children's Hospital Zürich)
Joshua Rabinowitz (Princeton University)
Collaborative projects are at the heart of our research. We partner with leading hospitals and research institutions worldwide to advance the understanding of cancer metabolism and develop innovative treatment approaches.
Selected Collaborators
Support
Let's Work Together
We believe the best science happens through collaboration. Whether you're a fellow researcher, clinician, or student with a curious mind, we'd love to connect. Let's join forces to bring new ideas to life.
Location
August-Forel-Strasse 51
8008 Zürich
Switzerland
Contact
raphael.morscher at kispi.uzh.ch
Tel: +41 44 249 49 49
© 2025 Morscher Lab
Contact
raphael.morscher at kispi.uzh.ch
Tel: +41 44 249 49 49
Location
August-Forel-Strasse 51
8008 Zürich
Switzerland
We believe the best science happens through collaboration. Whether you're a fellow researcher, clinician, or student with a curious mind, we'd love to connect. Let's join forces to bring new ideas to life.
Let's Work Together
© 2025 Morscher Lab
