Complex interactions among genes, proteins, and metabolites are needed to maintain cellular homeostasis. Despite numerous feedback and compensatory mechanisms in place to sustain normal cell function, stress conditions that includes exposure to drugs and other chemicals or underlying genetic changes may alter cellular function leading to disease or even death.
The research group discovered the enzyme GPCPD1 (EDI3), and showed its expression to be high in primary tumours of endometrial cancer patients who developed metastasis. Subsequent work identified EDI3 as a glycerophosphodiesterase that hydrolyses the glycerophosphodiester, glycerophosphocholine (GPC) to choline and a phosphorylated alcohol, glycerol-3-phosphate (G3P). Choline is a critical nutrient for liver and nerve function, and its metabolism is impaired in several diseases. It is also a precursor for the synthesis of phosphatidylcholine, the most abundant phospholipid in cell membranes. Altered choline metabolism has been documented in several cancers, and a low-choline diet has been associated with muscle damage, liver damage, and non-alcoholic fatty liver disease. G3P is important in both glycerophospholipid and triglyceride metabolism, with effects on glucose metabolism, lipid signal transduction, and lipogenesis.
Ongoing research in the CellMet group studies the enzymes in choline and glycerophospholipid metabolism, focusing on EDI3 as an important link between both pathways. The researchers continue to explore how altered expression and activity of EDI3 and related proteins and enzymes contribute to tumor growth and progression, focusing on breast and ovarian cancer. They also focus on EDI3’s role in embryonic development as mice lacking Edi3 do not survive postnatally. Finally, the physiological role of EDI3 is still being elucidated with studies addressing whether its metabolic function may be linked evidence of its involvement in glucose and acetylcholine metabolism.
The team of the group "Cellular Metabolism" (from left to right):
- Defne Göcener (Technical Assistant)
- Dr. Özlem Demirci (Scientist, 2021-2023)
- Dr. Annika Glotzbach (Scientist)
- Dr. Rosemarie Marchan (Groupleader)
- Anastasia Gonscharow (PhD student)
- Katharina Rohlf (PhD student)
- Simon Lücke (Technical Assistant)
- Manuel Álvarez de las Heras (PhD student)