Group Marinoni, Perren, Sadowski

The research focus of our group is the study of endocrine tumors; notably sporadic and familial pancreatic neuroendocrine tumors (PanNETs). PanNETs are highly heterogeneous and the mechanisms leading to tumor development are still elusive.
We focus on the understanding of the molecular events leading to PanNET formation and progression as well as on the investigation of the mechanisms mediating therapy resistance and tumor aggressiveness. We integrate molecular biological (in vitro and in vivo) and clinical (human tissue based ex vivo) research approaches.

Current research projects

Epigenetic changes and tumor cell heterogeneity in the progression of PanNETs

Group Perren We focus on understanding epigenetic changes occurring in PanNET and their impact on progression and metastasis formation. Based on DNA methylation we identified subgroups of PanNETs with: specific cell of origin, genetic background and clinical outcome. Integrating epigenetic and transcriptomic profiles we found that cell dedifferentiation and metabolic changes characterize progression from small PanNET to more advanced ones. We are currently investigating spatial and temporal heterogeneity of PanNET using multi-omic approaches.


Top: Phyloepigenetic analysis of PanNET human samples and normal alpha and beta-cell samples.  Bottom: Progression model hypothesis based on epigenetic and genetic evolution

Precision medicine approach for PanNET treatment

Group Perren Up to date, no therapy prediction based on specific molecular profile is possible for PanNET patients. We recently established patient-derived tumoroid cultures from PanNET patients which resemble features of original tumor tissue and which can be used for in vitro drug screenings. We are currently assessing the utility of PanNET tumoroids to predict patient therapy response and to identify novel epigenetic treatment options. Also, we aim at identifying specific molecular profiles through DNA sequencing, methylation- and gene expression analysis to predict therapy response in vitro and on the patients.


Patient-derived Tumoroids from PanNET patients are utilized for in vitro pharmacotyping and molecular profiling

Metabolic changes in PanNET

Group Perren Critical metabolic changes are early hallmarks of cancer cells. Emerging epigenetic, transcriptional and translational data suggest that PanNET cells undergo substantial metabolic reprogramming. However, the identity, functional consequences and therapeutic potential of metabolic changes in PanNET remain up until now largely unknown and untested. Our multimodal, integrated analysis of PanNET cell culture and tissue samples of various stages of tumor development by modern mass spectrometry, fluorescence microscopy and RNAseq data will delineate these metabolic and test novel therapeutic strategies.      


Tissue mass spectrometry (top) identified five metabolic PanNET. Fluorescence microscopy measured mitochondrial activity (middle) and lipid storage (bottom) in PanNET cells

An early offensive against acquired therapy resistance in PanNET

Group Perren Acquired drug resistance (ADR) is a major clinical challenge to all current cancer treatments, including chemo, radiation, targeted, and immune therapies and accounts for 90% of cancer mortality. Given the stochastic, mutation-driven nature of ADR, multiple different resistance mechanisms often co-evolve within in the same tumour or across metastatic lesions in the same patient, requiring individualized therapeutic approaches. This project seeks to identify and test novel strategies to target drug- tolerant persister cells (DTPs), which comprise an early, reversible bottleneck phase of ADR. RNAseq and high content imaging-guided molecular and phenotypic analysis will delineate the early dynamic changes during DTP development in 2D and 3D ADR models of PanNET.

Graphical description of the three phases of acquired drug resistance and associated phenotypes (right) with corresponding micrographs (left) of chronically treated PanNET spheroids showing hallmarks of DTPs (enhanced lipid peroxidation).


First and third price for best oral presentation at ENETs Annual Conference 2022

Ilaria Marinoni was awarded with the first price for the best oral presentation of her project "(Epi) genetic progression steps in alpha-lineage MEN1-DAXX/ATRX mutated Pancreatic Neuroendocrine Tumors (PanNET)" at the 1st International NET forum.
Simon April was awarded with the third price for the best oral presentation on his PhD project "Patient-derived Tumoroids phenocopy original GEP-NENs & facilitate in vitro drug screening".

Award for best research project & presentation at 15th Annual Meeting Swiss Stem Cell Network 2020

Featuring this year’s theme of “Organoid & other specialized cell cultures for clinical applications” Simon April-Monn (PhD Candidate, Gruppe Perren/Marinoni) was honored for his project on Patient-derived Islet-like Tumoroids and personalized medicine in PanNETs. The award was generously conferred by the co-hosts Bern Stem Cell Research and Regenerative Medicine (SCRM) & Bern Center for Precision Medicine (BCPM). 11.Dec.2020, Bern.