Head
Members of the Cellular Toxicology group have a primary interest in understanding metabolism, in particular phospholipid and choline, and the key enzymes involved in regulating these metabolic pathways. A major goal is also to elucidate how metabolism is altered in response to cellular stressors as well as in disease.
Phospholipids are important membrane constituents, energy sources, and signaling molecules – all of which are essential for maintaining cellular homeostasis. They are thus relevant in the context of cellular damage.
Our interest in phospholipid metabolism and its regulation began with the identification of a previously uncharacterized enzyme that was found to be elevated in the tumors of endometrial cancer patients who went on to develop metastasis, which we called EDI3 (Endometrial Cancer Differential 3) (Stewart et al., 2012). Our early work showed that EDI3 is a glycerophosphodiesterase (Stewart et al., 2012) that hydrolyzes glycerophosphocholine (GPC) – a breakdown product of phosphatidylcholine – to choline and glycerol-3-phosphate. In vitro analyses also demonstrated a role for EDI3 in cellular migration, adhesion and spreading (Stewart et al., 2012; Lesjak et al., 2014). Both of EDI3’s products can be reused in several metabolic pathways (Marchan et al., 2012), and recent work showed that the pathway downstream of the G3P product is relevant for the migration phenotype (Marchan et al., 2017). Ongoing studies continue to characterize EDI3 (GPCPD1; GDE5; GDPD6) and related enzymes in the glycerophospholipid metabolic pathway to understand their physiological role in maintaining cellular homeostasis, as well as under stress conditions and disease, especially cancer.
Major projects include:
- Characterizing a role for EDI3 in metastasis in vivo (DFG grant HE:2509/10-1).
- Characterizing a role for glycerophospholipid metabolism in ovarian cancer.
- Characterization of EDI3 knockout mouse.
- Investigating the relevance of EDI3’s carbohydrate binding domain in glycogen metabolism.
Over the years, members of the Cellular Toxicology as well as the newly branched out Inter-Organ Toxicology group, have developed and implemented several different techniques that allows the systematic evaluation of cellular responses upon stress stimuli. Other activities by the group include:
- Collection of clinically-relevant patient datasets, for the potential identification of relevant genes and pathways deregulated in these diseases, as well as for hypothesis generation
- The establishment of in vivo relevant models of cancer – xenografts and metastasis – to address questions on the role of particular genes and pathways in a particular type of cancer.
- The development of in vitro tools, based on cell and molecular biology approaches, to answer mechanistic studies on single genes and/or pathways and/or stress induction.
- Statistical analysis of transcriptomics data from self-generated or publicly-available data (in collaboration with the Statistics Department at the TU Dortmund)
- Close collaborations with other groups within the institute, such as the Analytical Chemistry Unit, Immunology and Neurotoxicology groups, well as maintaining fruitful collaborations with scientists both nationally and internationally.
Third-party funds
|
Financial year |
Funding source |
|
2012-2015 |
EU, Body on a Chip* |
|
2016-2019 |
DFG (HE2509) |
|
2020-2023 |
Deutsche Krebshilfe* |
* shared with research group ‘Systems Toxicology‘
