Lund Group
The aim of the laboratory is to unveil fundamental biological mechanisms and understand how these become perturbed during diseases, with the ambition that our findings may contribute to the development of clinical tools.
Specialized translation
Protein synthesis is essential for all cellular processes, and it is pivotal to understand how protein synthesis is regulated to facilitate differentiation and establish cellular identity. Importantly, the translation system is deregulated or hijacked in many diseases, and understanding how deregulated protein synthesis contributes to the development of disease may facilitate new therapeutic approaches.
The central ribosomal RNA structures are among the evolutionarily oldest biomolecules known, and in mammalian cells the ribosome is the most abundant organelle with up to 10 million ribosomes per cell. Furthermore, the mammalian ribosome is a central hub for many cellular functions beyond translation, such as stress sensing, and mRNA and protein quality control. Recent evidence has established that there is not only one type of ribosome, but that ribosomes across all kingdoms of life are heterogeneous at the level of ribosomal protein variants, accessory factors, or RNA modifications, and hence that several ribosome subtypes exist.
We work to decipher how different ribosome subtypes are established and composed at the molecular level, and how this impacts translational specialization and the establishment of translation programs.
We work across many biological model systems and diseases, including colorectal cancer, pancreatic cancer, glioblastoma, stem differentiation, and neuronal models. In addition, we develop computational and experimental tools to further our research efforts.
- Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions.
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Häfner SJ et al. Dev Cell 2023
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- Translational control through ribosome heterogeneity and functional specialization.
- Gay et al. Trends in Biochemical Sciences 2021.
- Gay et al. Trends in Biochemical Sciences 2021.
- Regulation of translation by site-specific ribosomal RNA methylation.
- Jansson et al. Nature Structural and Molecular Biology 2021
- Jansson et al. Nature Structural and Molecular Biology 2021
- The lncRNA MIR31HG regulates the senescence associated secretory phenotype.
- Montes et al. Nature Communication 2021.
- Repeat RNAs associate with replication forks and post-replicative DNA.
- Gylling et al. RNA 2020
- A high-throughput screen identifies the long noncoding RNA DRAIC as a regulator of autophagy.
- Tiessen et al. Oncogene 2019.
- Eukaryotic translation initiation factor 5A mediates translational control of autophagy via ATG3.
- Lubas et al. EMBO Reports 2018.
- Profiling of 2’-O-Me in human rRNA reveals a subset of fractionally modified positions and provides evidence for ribosome heterogeneity.
- Krogh, Jansson et al. NAR 2016.
- SNHG5: A lncRNA promoting tumor cell survival in colorectal cancer
- MIR31HG: A long non-coding RNA modulating senescence
- A microRNA regulating lysosomal function
- PRDM11: A new tumor suppressor
- Translational codes identified in the genome
- A microRNA impacting on p53
Ribosome modifications
We are addressing the hypothesis that modifications of the ribosomal RNA alter ribosome function and impose selective translation. Towards that, we previously demonstrated that modifying only a single modification can impact translation programs and affect cell fate decisions. Hence, specifically modified ribosomes may be functionally specialized to carry out translational programs of importance for establishing cellular identity and maintain cell homeostasis. We explore these ideas using cell culture model systems, stem cell differentiation models, neuronal models, mouse models, patient samples, and various organoid and spheroid models. We use a broad spectrum of genetic, computational, and biochemical techniques, such as RiboMethSeq, ribosome profiling, single molecule nanopore sequencing, and human in vitro translation systems.
Inhibiting onco-ribosomes
Protein synthesis is altered in cancer and several cancers are dependent on a high level of translation. We find that cancer cells and genetic mouse models for cancer display a different pattern of rRNA modifications as compared to their normal counterparts. As these modifications may affect ribosome structure and the association of factors to the ribosome, this provides opportunity for selective inhibition of ribosomes enriched in cancer. Together with collaborators, we conduct different screening approaches to identify compounds that selectively inhibit ribosomes with disease-related rRNA modification patterns.
Development of new base calling algorithm for detection and quantification of 2’O-me from Nanopore direct RNA sequencing.
In this project, we focus on the ribosomal heterogeneity that stems from the rRNA modifications, specifically 2´-O-methylations. Previously, in Lund lab, we have showed the importance of a single 2Ome modification on cell fate decisions, and with this project, we aim to expand our research to discover the effects of the combinatorial abundance of 2Omes on the same rRNA molecule. Therefore, in this project, we are creating machine learning models to predict the 2Ome abundance on rRNAs by using direct RNA nanopore sequencing data.
Selected publications
Ribosomal RNA 2'-O-methylation dynamics impact cell fate decisions. Häfner SJ, Jansson MD, Altinel K, Andersen KL, Abay-Nørgaard Z, Ménard P, Fontenas M, Sørensen DM, Gay DM, Arendrup FS, Tehler D, Krogh N, Nielsen H, Kraushar ML, Kirkeby A, Lund AH. (2023).
The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options. Groenewald W, Lund AH, Gay DM. (2023).
Translational control through ribosome heterogeneity and functional specialization. David M. Gay, Anders H. Lund, Martin D. Jansson.(2021).
The lncRNA MIR31HG regulates the senescence associated secretory phenotype. Montes, M., Lubas, M., Arendrup, F.S., Mentz, B., Rohatgi, N., Tumas, S., Harder, L.M., Skanderup, A.J., Andersen, J.S., and A.H. Lund. (2021).
Regulation of translation by site-specific ribosomal RNA methylation. Jansson, M.D., Häfner, S.J., Altinel, K., Tehler, D.E., Krogh, N., Jacobsen, E., Andersen, J.V., Andersen, K.L., Ménard, P., Nielsen, H., and A.H. Lund. (2020). Preprint.
Repeat RNAs associate with replication forks and post-replicative DNA. Gylling, H.M., Gonzalez-Aguilera, C., Smith, M.A., Kaczorowski, D.C., Groth, A., and A.H. Lund. (2020). RNA. doi:
10.1261/rna.074757.120.
A high-throughput screen identifies the long noncoding RNA DRAIC as a regulator of autophagy.
Tiessen, I., Abildgaard, M.H., Lubas, M., Gylling, H.M. Steinhauer, C., Pietras, E.J., Diederichs, S., Frankel, L.B*. and A.H. Lund* (2019). Oncogene, doi: 10.1038/s41388-019-0783-9.
Eukaryotic translation initiation factor 5A mediates translational control of autophagy via ATG3. Lubas, M., Harder, L.M., Kumsta, C., Tiessen, I., Hansen, M., Andersen, J.S., Lund, A.H.* and Frankel, L.B.* (2018). (*Co-corresponding authors). EMBO Reports, doi: 10.15252/embr.201846072.
Emerging connections between RNA and autophagy. Frankel, L.B., Lubas, M. and A.H. Lund (2016).. Autophagy. doi:10.1080/15548627.2016.1222992.
Ribosomes: a hidden key to understanding disease processes
12.09.2023
Oldest known molecule surprises researchers. It could lead to new important treatments
12.09.2023
Molecular hijacking: Cancer gene re-programs ‘protein factories’ to stimulate cell growth
23.11.2021
The ribosomes, the ‘protein factories’ in our cells, can be altered by cancer genes, a new study from the University of Copenhagen shows.
PUBLICATION SPOTLIGHT - The long non-coding RNA MIR31HG regulates the senescence associated secretory phenotype
27.04.2021
By Marta Montes Resano, Assistant professor, Lund Group.
09.04.2015
Professor Owen Sansom, Beatson Institute, UK
Professor Martin Bushell, Beatson Institute, UK
Dr. Miten Jain, Northeastern University, US
Professor Mark Akeson, UCSC, US
Dr. Hasindu Gamaarachchi, UNSW, Australia
Dr. Ira Deveson, The Garvan Institute of Medical Research, Australia
Dr. Kathrin Leppek, University of Bonn, DE
Professor Bjarne Kristensen, Rigshospitalet/BRIC UCPH, DK
Associate professor Luis Arnes, BRIC UCPH, DK
Dr. Lisa B. Frankel, Danish Cancer Institute, DK
Professor Henrik Nielsen, ICMM UCPH, DK
Professor Simon Holst Bekker-Jensen, ICMM UCPH, DK
Professor Mads Hartvig Clausen, Dept. Of Chemistry, DTU, DK
Professor Guillermo Montoya, CPR UCPH, DK
Professor Thomas Hamelryck, Dept. Biology, UCPH, DK
Professor Peter Brodersen, Dept. Biology, UCPH
Immagina Biotechnology
The lab is part of the Translational Control in Cancer European Network, TRANSLACORE
