von Felden Lab

AG von Felden


About us

We are a young and enthusiatsic junior research group located at the University Medical Center Hamburg-Eppendorf, Germany. 

As an independent group, our work focusses on translational research projects in the field of hepatobiliary oncology, with the main objective to derive molecular biomarkers for implementing personalized cancer care for patients with liver cancer. We aim at deciphering mechanisms of hepatocarcinogenesis and identifying biomarkers for risk startification,  early cancer detection, and to predict response to therapies. For this, we utilize state-of-the-art technologies and modern analytical pipelines, incl. liquid biopsy approaches and next-generation sequencing. 



We are happy to anounce that Dr. Johann von Felden has been selected for the Rising Star Award 2023 by the United European Gastroenterology (UEG).


Highlighted publications

Unannotated small RNA clusters associated with circulating extracellular vesicles detect early stage liver cancerObjective Surveillance tools for early cancer detection are suboptimal, including hepatocellular carcinoma (HCC), and biomarkers are urgently needed. Extracellular vesicles (EVs) have gained increasing scientific interest due to their involvement in tumour initiation and metastasis; however, most extracellular RNA (exRNA) blood-based biomarker studies are limited to annotated genomic regions. Design EVs were isolated with differential ultracentrifugation and integrated nanoscale deterministic lateral displacement arrays (nanoDLD) and quality assessed by electron microscopy, immunoblotting, nanoparticle tracking and deconvolution analysis. Genome-wide sequencing of the largely unexplored small exRNA landscape, including unannotated transcripts, identified and reproducibly quantified small RNA clusters (smRCs). Their key genomic features were delineated across biospecimens and EV isolation techniques in prostate cancer and HCC. Three independent exRNA cancer datasets with a total of 479 samples from 375 patients, including longitudinal samples, were used for this study. Results ExRNA smRCs were dominated by uncharacterised, unannotated small RNA with a consensus sequence of 20 nt. An unannotated 3-smRC signature was significantly overexpressed in plasma exRNA of patients with HCC (p<0.01, n=157). An independent validation in a phase 2 biomarker case–control study revealed 86% sensitivity and 91% specificity for the detection of early HCC from controls at risk (n=209) (area under the receiver operating curve (AUC): 0.87). The 3-smRC signature was independent of alpha-fetoprotein (p<0.0001) and a composite model yielded an increased AUC of 0.93. Conclusion These findings directly lead to the prospect of a minimally invasive, blood-only, operator-independent clinical tool for HCC surveillance, thus highlighting the potential of unannotated smRCs for biomarker research in cancer. Data are available in a public, open access repository. RNA-sequencing data have been deposited in the ArrayExpress database at EMBL-EBI (www.ebi.ac.uk/arrayexpress) under accession numbers E-MTAB-8528 and E-MTAB-8529. Code availability statement: all code will be made publicly available at Dr Losic GitHub site.
Liquid biopsy in the clinical management of hepatocellular carcinomaWith increasing knowledge on molecular tumour information, precision oncology has revolutionised the medical field over the past years. Liquid biopsy entails the analysis of circulating tumour components, such as circulating tumour DNA, tumour cells or tumour-derived extracellular vesicles, and has thus come as a handy tool for personalised medicine in many cancer entities. Clinical applications under investigation include early cancer detection, prediction of treatment response and molecular monitoring of the disease, for example, to comprehend resistance patterns and clonal tumour evolution. In fact, several tests for blood-based mutation profiling are already commercially available and have entered the clinical field. In the context of hepatocellular carcinoma, where access to tissue specimens remains mostly limited to patients with early stage tumours, liquid biopsy approaches might be particularly helpful. A variety of translational liquid biopsy studies have been carried out to address clinical needs, such as early hepatocellular carcinoma detection and prediction of treatment response. To this regard, methylation profiling of circulating tumour DNA has evolved as a promising surveillance tool for early hepatocellular carcinoma detection in populations at risk, which might soon transform the way surveillance programmes are implemented. This review summarises recent developments in the liquid biopsy oncological space and, in more detail, the potential implications in the clinical management of hepatocellular carcinoma. It further outlines technical peculiarities across liquid biopsy technologies, which might be helpful for interpretation by non-experts.