Our studies aim to analyse gene function in healthy and pathological conditions, e.g. in tumour development, using the mouse as a model organism, but also employing patient-derived samples. Our overall strategic goals are to achieve a better understanding of the events leading to disease and to discover molecular mechanisms that could provide a basis for novel therapies. We investigate how a healthy organ functions within a complex organism focussing on the liver, skin and bone but we also study inflammation, fibrosis, metabolism, tumorigenesis and cancer cachexia.
Our research covers multiple aspects of cell biology, ranging from stem cells, tumour cell interactions with host cells/environment such as tumour-associated macrophages and fibroblasts. Powerful state-of-the-art mouse genetic models, human cellular systems, high-throughput genomic/proteomic and biochemical tools as well as patient-derived materials are employed. For example, genes encoding for the transcription factor complex AP-1 (Fos/Jun) were manipulated in mouse models to study diseases such as psoriasis, systemic fibrosis, arthritis, hepatocellular carcinoma and osteosarcoma.
The aim is to define molecular pathways leading to disease development and to identify novel therapeutic targets (FIGURE). We focus on:
- Elucidating a causal link between inflammation, cancer and AP-1 (Fos/Jun) expression, using cell type-specific, switchable genetically engineered mouse models (GEMMs).
- Developing and characterising new GEMMs for cancer and human diseases, such as psoriasis, arthritis and fibrosis, and applying these to preclinical studies.
- Using multiple approaches to compare mouse models of disease to human disease and to identify therapeutically relevant targets.