Dissecting the role of metabolic alterations in sphingolipids in pancreatic ductal adenocar- cinoma (PDAC)”

• Applicant: Professorin Dr. Julia Mayerle
• Subject Area: Gastroenterology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 517022033

Sphingolipids, including the two central bioactive lipids, ceramide, and sphingosine-1-phosphate (S1P), have opposing roles in regulating cancer cell death and survival in PDAC. However, cellular and molecular determinants regulating selectivity of one sphingolipid metabolite over the other are poorly understood. We will work on the following three main objectives: (1) To understand causes and consequences of the pancreas specific role of the yin and yang of sphingomyelin metabolism (Smpd1 and Asah1). (2) To understand the relationship between metabolic changes in the sphingolipid pathway and its associated cellular context. (3) To understand the contribution of compensatory sphingolipid pathways influencing sphingolipid metabolism in relation to membrane fluidity. This will allow us for the first time to systematically identify sphingolipid-related genes and their positive and negative regulators that influence membrane fluidity acting as triggers for neoplastic transformation and treatment resistance.

• DFG Programme: Research Grants
• Co-Investigator: Ujwal Mukund Mahajan, Ph.D.