A5047787641- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- IL-33, ST2, and ILC Pathways
- TGF-β signaling in diseases
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Tracheal and airway disorders
- Genetic factors in colorectal cancer
- Cancer-related gene regulation
- Renal and related cancers
- Cell Adhesion Molecules Research
- Cancer Research and Treatments
- CRISPR and Genetic Engineering
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Advanced Breast Cancer Therapies
- Extracellular vesicles in disease
- Neonatal Respiratory Health Research
- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- Endoplasmic Reticulum Stress and Disease
Heidelberg University
2015-2025
Heidelberg Institute for Stem Cell Technology and Experimental Medicine
2015-2025
Universitat de Barcelona
2022-2024
Institut d'Investigació Biomédica de Bellvitge
2022-2024
Instituto Oncológico Dr. Rosell
2024
DKFZ-ZMBH Alliance
2016-2023
German Cancer Research Center
2015-2023
Deutschen Konsortium für Translationale Krebsforschung
2020-2022
Bellvitge University Hospital
2022
Universitätsmedizin Göttingen
2021
Significance Pancreatic ductal adenocarcinoma is one of the most malignant human tumors for which there are no efficacious therapeutic strategies. This tumor type characterized by an abundant desmoplastic stroma that promotes progression. Yet recent studies have shown physical or genetic elimination leads to more aggressive development. Here, we decided reprogram stromal tissue identifying and subsequently targeting genes responsible their protumorigenic properties. Comparative transcriptome...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is characterized by extensive desmoplasia, which challenges the molecular analyses of bulk tumor samples. Here we FACS-purified epithelial cells from human PDAC and normal pancreas derived their genome-wide transcriptome DNA methylome landscapes. Clustering based on methylation revealed two distinct groups displaying different patterns at regions encoding repeat elements. Methylationlow tumors are higher expression endogenous retroviral...
Ferroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens hypersensitive cells, we identify selenoprotein P (SELENOP) receptor, LRP8, a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to result insufficient supply selenocysteine, which is required...
A temporal systems biology screen of premetastatic endothelial cells identified LRG1 as a therapeutic target for restricting metastases.
Pancreatic ductal adenocarcinoma (PDAC) frequently metastasizes into the peritoneum, which contributes to poor prognosis. Metastatic spreading is promoted by cancer cell plasticity, yet its regulation microenvironment incompletely understood. Here, we show that presence of hyaluronan and proteoglycan link protein-1 (HAPLN1) in extracellular matrix enhances tumor plasticity PDAC metastasis. Bioinformatic analysis showed HAPLN1 expression enriched basal subtype associated with worse overall...
The acquisition of mesenchymal traits is considered a hallmark breast cancer progression. However, the functional relevance epithelial-to-mesenchymal transition (EMT) remains controversial and context dependent. Here, we isolate epithelial populations from human metastatic biopsies assess their potential in vivo. Strikingly, progressively decreasing cell adhesion molecule (EPCAM) levels correlate with declining disease propagation. Mechanistically, find that persistent EPCAM expression marks...
Due to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent preferred route improve prognosis pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis PDAC precursors aiming at dissecting process carcinogenesis and tackling heterogeneity preinvasive lesions.
Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of evades the system is crucial for advancing novel therapies.
Brain organoids (BO) have risen as a reliable model for neurodelopmental disorders (ND), reproducing human brain development milestones. However, their significant intra- and inter-organoid variability compromises use in advanced tasks such drug testing. Overcoming experimental is crucial models prone to variation, like unguided BO. BO modelling Dravet Syndrome, late-onset epileptic ND, represents great challenge since accumulates with time, when phenotype shows vitro. Leveraging deep...
We describe herein non-integrating minimally sized nano-S/MAR DNA vectors, which can be used to genetically modify dividing cells in place of integrating vectors. They represent a unique genetic tool, avoids vector-mediated damage. Previous work has shown that vectors comprising mammalian S/MAR element provide persistent mitotic stability over hundreds cell divisions, resisting epigenetic silencing and thereby allowing sustained transgene expression. The composition the original does present...
Pancreatic ductal adenocarcinoma (PDAC) has been subclassified into 3 molecular subtypes: classical, quasi-mesenchymal, and exocrine-like. These subtypes exhibit differences in patient survival drug resistance to conventional therapies. The aim of the current study is identify novel subtype-specific protein biomarkers facilitating subtype stratification patients with PDAC therapy development.A set 12 human patient-derived primary cell lines was used as a starting material for an advanced...
Abstract HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes of AKT and ERK1/2, contributing to tumour progression therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, although they have shown favorable tolerability, their activity as a single agent has proven be limited. Here we show phosphorylation cells occurs paracrine manner mediated cancer-associated fibroblasts (CAFs). Moreover,...
xCT (Slc7a11), the specific subunit of cystine/glutamate antiporter system x
Abstract Despite important advances in the treatment of breast cancer, 5-year survival rate for patients with distant metastasis remains less than 30%. Metastasis is a complex, multi-step process beginning local invasion and ending outgrowth systemically disseminated cells into actively proliferating metastases that ultimately cause destruction vital organs. It this last step limits patient and, at same time, least understood mechanistically. Here, we focus on understanding determinants...
Gold, palladium and platinum complexes with an unusual isocyanide ligand containing a carboxylic acid function, [AuCl(CNC6H4COOH)], cis-[MI2(CNC6H4COOH)2] trans-[MI2(CNC6H4COOH)2] (M = Pd, Pt) have been isolated. The group of the coordinated acts as hydrogen donor for hydrogen-bonding three series stable hydrogen-bonded liquid crystalline metal prepared decyloxystilbazole. Although all derivatives used are not mesomorphic, decyloxystilbazole only shows ordered Smectic E phase, four out five...