Delphine Burggraeve

Advanced hepatocellular carcinoma (aHCC) is a lethal disease and, due to its high incidence, a major global health concern. Because of late clinical presentation and underlying liver disease, most HCC patients are diagnosed at intermediate or advanced stages, where curative treatment options are limited and prognosis is poor. Current therapies, mainly immunotherapy using immune checkpoint inhibitors (ICIs) and, secondarily, tyrosine kinase inhibitors (TKIs), provide only modest survival benefits, are effective in a minority of patients, and often lead to rapid resistance and severe side effects. Consequently, novel combination therapies are urgently needed.

My PhD research aims to develop preclinical evidence for new combination therapies in aHCC by targeting deubiquitinases (DUBs), which are druggable enzymes regulating oncoproteins, in combination with approved treatments such as TKIs and/or ICIs. Building on a proof-of-concept study showing that DUB inhibition with a TKI induces synergistic cytotoxicity in vitro and in vivo, the project seeks to elucidate the molecular basis of this synergy and uncover resistance mechanisms using a comprehensive multi-omics approach, including transcriptomics, proteomics, phosphoproteomics, ubiquitinomics, and interactomics. Additionally, this integrative approach could identify potential biomarkers predictive of response to DUB inhibition–based therapies, and potentially uncover additional DUB targets relevant to aHCC. A secondary aim of the project is to advance patient-oriented research by utilizing patient-derived materials to develop personalized prognostic models. These models could be used to evaluate specific drug combinations, such as DUB inhibition, and to guide personalized treatment decisions for patients with aHCC. The ultimate aim of this project is to translate this new combination therapy toward clinical trials, thereby expanding treatment options for patients with aHCC. 
 

• Master’s degree in Biomedical Science
   

• Lab address:
  1. VIB-UGent Center for Medical Biotechnology, FSVM II Research building, Technologiepark-Zwijnaarde 75, 9052 Ghent 
  2. UZ Ghent, Corneel Heymanslaan 10, entrance 36, 9000 Ghent
• LinkedIn
• Department of Internal Medicine and Pediatrics
• Department of Biomolecular Medicine
• Delphine Burggraeve is interested to receive invitations for presentations or talks