Education and Training
Rocio Sotillo is the head of the division of Molecular Thoracic Oncology at the German Cancer Research Center (DKFZ) and a full professor at Heidelberg University Medical Faculty. After graduating in Pharmacy at the San Pablo-CEU University (Spain), she conducted her PhD at the Spanish National Cancer Center (CNIO) in Madrid. She was a postdoc at Sloan Kettering Cancer Center in New York and a Staff Scientist at EMBL-Rome.
Expertise
The Sotillo group has a long-standing interest in human lung cancer by applying genomic and functional approaches to study lung adenocarcinoma in innovative mouse models including recent efforts on modelling Eml4-Alk-driven lung cancer. In addition, the group has an interest in cancer aneuploidy and chromosome instability. They have shown that overexpression of the mitotic checkpoint gene Mad2 causes chromosome instability, which in turn facilitates the development of recurrent tumors and the emergence of resistant subclones in certain cancer models.
- Cell of origin of lung adenocarcinoma
- Lung cancer resistant mechanisms
- Identification of EML4-ALK vulnerabilities
Lung Cancer
- Diaz-Jimenez, A., Shuldiner, E. G., Somogyi, K., Gonzalez, O., Akkas, F., Murray, C. W., Andrejka, L., Tsai, M. K., Brors, B., Sivakumar, S., Sisoudiya, S. D., Sokol, E. S., Petrov, D. A., Winslow, M. M., & Sotillo, R. (2024). EML4-ALK variant-specific genetic interactions shape lung tumorigenesis. BioRxiv, 2024.08.26.609730. (accepted, Cancer Discovery, 2025)
- Diaz-Jimenez A, Ramos M, Helm B, Chocarro S, Frey DL, Agrawal S, Somogyi K, Klingmüller U, Lu J, Sotillo R. Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome. Drug Resist Updat. 2024 May;74:101081. doi: 10.1016/j.drup.2024.101081.
- Horvat NK, Chocarro S, Marques O, Bauer TA, Qiu R, Diaz-Jimenez A, Helm B, Chen Y, Sawall S, Sparla R, Su L, Klingmüller U, Barz M, Hentze MW, Sotillo R*, Muckenthaler MU*. Superparamagnetic Iron Oxide Nanoparticles Reprogram the Tumor Microenvironment and Reduce Lung Cancer Regrowth after Crizotinib Treatment. ACS Nano. 2024 Apr 30;18(17):11025-11041. doi: 10.1021/acsnano.3c08335.
- Alonso de la Vega A, Temiz NA, Tasakis R, Somogyi K, Salgueiro L, Zimmer E, Ramos M, Diaz-Jimenez A, Chocarro S, Fernández-Vaquero M, Stefanovska B, Reuveni E, Ben-David U, Stenzinger A, Poth T, Heikenwälder M, Papavasiliou N, Harris RS, Sotillo R. Acute expression of human APOBEC3B in mice results in RNA editing and lethality. Genome Biol. 2023 Nov 24;24(1):267. doi: 10.1186/s13059-023-03115-4.
- Kandala S, Ramos M, Voith von Voithenberg L, Diaz-Jimenez A, Chocarro S, Keding J, Brors B, Imbusch CD, Sotillo R. Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer. Cell Rep. 2023 Dec 26;42(12):113266. doi: 10.1016/j.celrep.2023.113266.
Kalman Somogyi | Postdoc |
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Maria Ramos | PhD student |
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Mulham Najarejh | PhD student |
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Mayte Castillo | PhD student |
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Maria Capone | PhD student |
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Amelie Mahr | PhD student |
Lung Research - Projects
- Tracking resistance in ALK-positive non-small cell lung cancer.
The majority of ALK (anaplastic lymphoma kinase) -positive lung cancer patients develop mutations in the ALK kinase domain that confer resistance to ALK targeting therapies. In the clinical settings resistance can only be determined at endpoints making it almost impossible to analyse dynamic adaptation, selection and tumor evolution under therapy. It is therefore important to establish biomarkers and to predict responses and treatment failures based on molecular features to optimised ALK-directed therapy. The team is employing ALK-driven lung cancer mouse models to gather information on the in vivo response to ALK inhibitor treatment. - Identification of the cell-of-origin of ALK-driven lung adenocarcinoma.
During the last years, the ground-breaking success of checkpoint blockade as well as targeted therapies in non-small cell lung cancer have dramatically improved survival rates. However, the cells that initiate tumors, their genomic landscape and their interaction with the tumor microenvironment are not well defined. The team has used state-of-the-art mouse models combining lineage tracing and genome editing technologies to create a stochastic, cell lineage traceable EML4-ALK lung cancer model. Using this model, they have identified club cells and alveolar type 2 cells to be the initiating cells in lung adenocarcinoma formation. To gain more insights regarding these cell types, the group is performing whole genome bisulfite sequencing and RNA sequencing from normal cells (from which the tumor cells originate) and tumors per se. By subsequent bioinformatics analysis, the team will be able to identify those genomic regions/genes whose methylation status/expression level is unchanged during tumorigenesis, which can serve as the marker for the cell-of-origin of lung cancer. - Development of 3D culture systems of lung cancer
3D culture systems reproduce cellular complexity and spatial organization of the lung tissue. The team is using 3D cultures of mouse tumor cells as well as patient derived cells to analyse the effects of drug combinations that might result in better treatment response.
