During the PhD I developed an increasing interest in translational oncology and therefore I decided to move my research on this field. In 2020 while I was looking for a Postdoctoral position I met Dr. Carmine Carbone and Dr. Geny Piro that invited me to join them at the Medical Oncology group at Fondazione Policlinico Universitario “Agostino Gemelli” lead by Prof. Giampaolo Tortora. Our group have several translational projects on different types of tumor, yet I’m mostly involved in pancreatic cancer research because I was fascinated, and terrified, by its incredible complex system of interactions between the cancerous cells and the cells of the microenvironment. This complexity however is an intriguing puzzle to be solved by computational biologists like me using sometimes even more complicated algorithms, that are however are my cup of tea.

As a computational biologist I’m involved in several projects from our group ranging from the development of novel therapies for pancreatic cancer to the study of its oncogenesis and development. Our group believes that a multi-omic approach is essential to provide an in-depth understanding of pancreatic cancer, therefore we use a compendium of multi-omics technologies such as targeted and untargeted proteomics and metabolomics, Nanostring platforms, single cell RNA-seq and beyond. The research project that I’m mostly involved in is the spatial transcriptomic characterization of Intraductal Papillary Mucinous Neoplasm (IPMN) that is part of Dr.Carbone AIRC MFAG project. These lesions are the precursor of pancreatic cancer and we wanted to study their degeneration from a benign neoplasm to a heinous cancer. We started thinking about the problems that usually affect projects about IPMN, such as the availability of only FFPE samples, the small dimensions of these lesions and their scarce cellularity, and we decided to move from a bulk approach to a technology with a far better resolution. We found a solution in spatial transcriptomics and in particular in the Visium FFPE application from 10X Genomics. This technology gives the opportunity to build spatially-coded RNA-sequencing libraries to obtain a spatial map of the transcriptome with a resolution of 55 µm.  We built a tissue array to be analyzed with Visium gathering benign IPMN, intended as lesions originated from patients that never developed pancreatic cancer, and malignant IPMN with their associated PDAC. The entire process was not easy and took us almost 6 months to develop a robust protocol to achieve good results; but the findings that we have now are amazing. We have found the main transcription factors that lead from low-grade and indolent IPMN to the high-risk. Moreover, we found a plethora of gene markers associated with the different morphology of IPMN and their grade of malignancy. We validated these results in collaboration with ICGC on a validation cohort of 57 IPMN analyzed with GeoMx, another spatial transcriptomics solution. All together these results shed more light on the early steps of pancreatic oncogenesis and other projects started on the basis of these exciting results. In fact, we are currently testing the function of the malignancy-associated genes in IPMN patient derived organoids established by Dr.Carbone, myself, and from Prof. Vincenzo Corbo group of the Italian –Pancreatic Cancer Community (IPCC).

Pancreatic cancer gives almost no chance of survival because in almost all cases presents at the late stage of disease. Even though IPMN may be detected in advance in some cases, it is not always easy for the clinicians to understand  if a lesion is malignant or not and to choose for the pancreatic resection or to wait and watch. However this period of clinical surveillance has a profound impact in the quality life of patients, that may suffer of severe anxiety and depression. Unfortunately, several studies showed tha surveillance may fail and patient develop pancreatic cancer. Despite the huge efforts that has been carried by the pancreatic cancer research community, there is no consensus about the markers that are the determinants of IPMN malignancy. If our results will be validated in other independent cohorts, not only we will have a deeper knowledge of IPMN development but we will also have prognostic markers to be evaluated at the time of decision. We hope that these markers that we have identified will help the decision making and prevent many cases of pancreatic cancer.

The I-PCC gave me to opportunity to share knowledge with researchers working on the same topic but on a different prospective. This sharing give me a new glimpse into the complexity of pancreatic cancer and make me view my projects from a bigger picture finding new ideas and strategies to tackle this incredible powerful foe.