Edoardo Giuili

Drug resistance continues to be an unyielding adversary in our ambition for curative cancer treatment. Historically, researchers have focused on identifying and understanding selection of genetic subclones driving drug resistance. While several mutational mechanisms of drug resistance have been identified, increasing evidence is emerging for the role of non-genetic resistance mechanisms, including epigenetic heterogeneity and plasticity. This evidence poses a new challenge to the field, that requires innovative strategies to monitor these adaptive processes and to identify new treatment options that target these resistance mechanisms and set up more dynamic therapeutic strategies, ultimately leading to better and longer-lasting clinical responses. 

Implementing these novel therapeutic strategies, however, requires new sensitive and preferably minimally invasive tools. The EpiGuide project will establish a minimally invasive tool to detect and monitor epigenetic biomarkers for therapy resistance of cancer patients. The envisioned EpiGuide assay aims to analyze epigenetic modifications present in circulating cell-free DNA (cfDNA) released by tumor cells into the blood plasma and translate this signal into the fractional presence of epigenetic cell states in the tumor through computational deconvolution. In addition to exploring the temporal and spatial dynamics of epigenetic switches in relation to drug resistance and patient outcomes, the long-term objective is to bring the EpiGuide assay into clinical practice and guide personalized and disease state-adapted therapy selection.

My main role within the EpiGuide project is to implement, benchmark and improve existing methods for computational deconvolution and explore new strategies to combine different layers of epigenetic information (i.e. methylation, histone modification and nucleosome occupancy patterns) for optimal prediction performance.
 

• Comprehensive evaluation of the implementation of episignatures for diagnosis of neurodevelopmental disorders (NDDs). Human Genetics, 2023. 
• Exploring the cell-free total RNA transcriptome in diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma patients as biomarker source in blood plasma liquid biopsies. Frontiers in Oncology, 2023. 
   

• Lab address:  De Preter lab, VIB-UGent Center for Medical Biotechnology, UGent-VIB Research Building, FSVMII, Technologiepark 75, 9052 Zwijnaarde, Belgium
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• Edoardo Giuili is interested to receive invitations for presentations or talks