Adenocarcinoma of the pancreas: investigation of the biology of early alterations and malignant transformation in mouse models.
Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal human malignancies. Despite its rather low incidence, it remains the fourth leading course of cancer death. This is mostly due to the difficult and late diagnosis, early metastatic spread and resistance to chemoradiation therapy. Therefore, identification of predictive markers for early diagnosis and new chemotherapy strategies for this illness are urgent goals. The activation of mutated, constitutive active KrasG12D in 90% of all human pancreatic ductal adenocarcinomas (PDACs) leads to the hypothesis that oncogenic KrasG12D is required for tumor initiation. However, signaling and cellular events taken place downstream of Kras are poorly understood. Emerging evidence suggests that acino-ductal metaplasia (ADM) is an important prerequisite for development of PDAC and precursor lesions such as pancreatic intraperitoneal neoplasia (PanIN) and ADM. In our studies, we use genetically modified mouse models that faithfully recapitulate the developmental milestone of PDAC observed in humans. It is our aim to elucidate the complex molecular events that lead to the initiation and development of PDAC in mice.
We focus on the role of fluid-phase endocytosis during ADM development and PDAC progression.Be means of genetic, molecular and cell biological methods we aim to address following questions:
1) Which molecular pathways couple endosomes with Kras signaling and PDAC progression?
2) Are endocytosis and metabolic processes linked during PDAC initiation and progression?
Publications ⎮ Medical theses ⎮ PhD ⎮ Grant support