Dr Vincenzo Corbo
Associate Prof. Dept of Diagnostics and Public Health, University of Verona, Italy
Vincenzo Corbo is group leader at the University of Verona since 2016. He received the master's degree in Biotechnology from the University of Naples and successfully completed his research PhD at the University of Verona in the laboratory of Prof Aldo Scarpa. Vincenzo completed his training as Post-Doc in the laboratory of David Tuveson at Cold Spring Harbor Laboratory, NY (USA), where he participated to the development of the three-dimensional organoid culture system to study pancreatic cancer. Following his Post-Doc, Vincenzo joined the Department of Diagnostics and Public Health at the University of Verona, where he has been appointed as Associate Professor in 2021. The Corbo laboratory uses different experimental models of pancreatic cancer to investigate the determinants of malignant progression with the ultimate goal of favouring the identification of new diagnostic and therapeutic approaches. Current projects focus on the identification and characterization of cell extrinsic factors and signalling pathways involved in the definition of the heterogeneous phenotypes of epithelial and non-epithelial cells in pancreatic cancer. He is recipient of grants from the AIRC (Italian Association for the study of Cancer), the European Union (PRECODE project) and has recently served as PI of the Italian Subsite of the Cancer Model Development Center funded by the National Cancer Institute (NCI, USA) within the frame of the Human Cancer Model Initiative (https://ocg.cancer.gov/programs/HCMI).
Differential activation of MAPK pathway in the stroma of pancreatic cancer subtypes
Based on mRNA profiling, two consensus molecular subtypes of pancreatic cancer have been proposed: the classical and the basal-like/squamous. In particular, classical tumours are characterized by expression of endodermal transcription factors (e.g., GATA6) and enriched for SMAD4 alterations; this is often considered as the default pancreatic cancer subtype. Basal-like/squamous PDAC is characterized by the loss of endodermal identity, increased TGF-β signalling, genomic instability, and it is enriched for inactivation of TP53 and chromatin modifiers. The ΔN isoform of p63 represents a master regulator of basal-like phenotype in PDAC. Regardless of the subtype, a dense fibrotic reaction with scant CD8+ T cells infiltration is a cornerstone of the PDAC TME. Cancer-associated fibroblasts (CAFs) are abundant within the PDAC stroma and a number of CAFs phenotypes has been recently reported. The existence of different phenotypes might explain the failure of the agnostic targeting of CAFs in the preclinical and clinical settings, and further highlight the necessity of mapping out CAFs heterogeneity to devise better therapies. Our laboratory seeks to identify subtype-specific features of stromal elements by combining unbiased approaches (single-cell sequencing, genomics) and hypothesis driven experiments (genetic and pharmacological perturbation analyses). Here, I will discuss recent insights on the differential activation of MAPK pathway in the stroma surrounding neoplastic cells of different qualities (basal-like vs classical) and how the pathway inhibition remodels the stromal and immune contexture of pancreatic cancer.