Research lines

• Understanding pancreatic carcinogenesis

  Directed by Dr. Cristina Fillat 

  Pancreatic carcinogenesis is well defined as a multistage process accompanied by distinct morphological and histological changes, resulting from molecular alterations that are acquired during malignant transformation. However, the functional impact of many of the deregulated molecules remains to be elucidated. We have recently shown the contribution of DYRK1A to pancreatic tumor progression by stabilization of the receptor tyrosine kinase c-MET. Currently, we are investigating other DYRK1A- dependent mechanisms that may signal to amplify its pro-tumorigenic role. 

• Oncolytic virotherapies against pancreatic cancer

  Directed by Dr. Cristina Fillat 

  Oncolytic adenoviruses replicate in the tumors leading to oncolysis and triggering an immune cell infiltration into the tumor that results in an antitumor response. We have developed oncolytic adenovirus designs that present high selectivity for pancreatic tumors and improved tumor replication,and shown its anti-cancer activity in patient-derived xenografts (PDX). We are now particularly interested in manipulating the viruses to permit efficient intravascular delivery, intratumor spread and engaging of the host immune system to generate more efficacious therapies for primary and metastatic tumors. We use a combination of PDX mouse models and an organoid platform to screen for the optimal designs. 

• Innovation in oncologic surgery and robotic pancreatic surgery

  Directed by Dr. Fabio Ausania 

  This line is centered on the NOVELLA project, integrating haemodynamic modelling (CFD/AI), preoperative imaging and intraoperative data in robotic pancreatic surgery to predict complication risk and personalize surgical strategy. It covers technology development, multicenter clinical validation and translation of NOVELLA-derived tools. This line has a clear focus on clinical impact, standardization and improved outcomes. 

• DYRK kinases: regulation and role in pancreatic cancer and other human disorders

  Directed by Dr. Susana de la Luna 

  Protein kinases are central to all cellular processes in eukaryotes and often linked to disease when altered. This research line focuses on the DYRK family of protein kinases, key regulators of cellular viability and homeostasis. Altered DYRK expression is associated with various cancers, while mutations are linked to developmental disorders such as DYRK1A haploinsufficiency syndrome. We investigate the molecular roles of DYRKs to understand how their dysregulated activity contributes to human pathology, particularly in the context of pancreatic cancer. 

• Preclinical gene therapy /genome editing studies for metabolic rare diseases

  Directed by Dr. Cristina Fillat 

  Glutaric aciduria type I (GA-I) is a metabolic inherited disease due to mutations in the GCDH gene. Individuals with GA-I are controlled by a dietary treatment. However, deficits in adherence to the treatment or lack of effectiveness in some patients result with a negative impact on the clinical outcome.  We are developing adeno-associated viral vectors (AAV) and explore the feasibility of an AAV-gene therapy approach in mouse models of GCDH deficiency. The results from this project may provide novel treatment options for GA-I.