About the group
We study the roles of the aryl hydrocarbon receptor (AHR) and its target gene, poly ADP-ribose polymerase 7 (PARP7/TIPARP), in normal physiology, metabolism, inflammation and cancer. Both proteins have important roles in regulating inflammation and immunity. In the context of cancer, AHR and PARP7 allow tumour cells to “hide” from the immune system giving them the opportunity to grow and proliferate. We are determining if inhibition of AHR or PARP7, alone or in combination with current immunotherapy treatments, reduces cancer growth and progression. We also study the AHR-PARP7 axis in chronic inflammatory diseases including obesity and atherosclerosis.
AHR and PARP7 regulate several metabolic and signalling pathways in response to cellular stress. Both proteins dampen inflammation and regulate immune signalling, which allow tumours to avoid immune regulation and proliferate. Recent studies show that small molecule inhibition of PARP7 or loss of AHR expression release the brake that cancer cells use to evade the immune system. By using cell biology, gene editing, genomics, and preclinical cancer models, we aim to determine the suitability of targeting AHR and PARP7 alone, in combination or with other immunotherapy treatments as new therapeutic options for cancer treatment.
Projects
- AHR-PARP7 in triple negative breast cancer progression
- Inhibition of AHR signaling in pancreatic cancer to increase susceptibility to PD-1/PD-L1 inhibitors and chemotherapy via ELAVL1 pathway
- Dietary prevention of cholesterol induced trained immunity in early atherosclerosis
- Role of PARP7 in energy metabolism
- Exposome trajectories in cardiovascular and metabolic non-communicable diseases (LongITools)
- Study on Diet in Pregnancy
Cooperation
- Bjørn Steen Skålhegg, University of Oslo
- Kirsten Bjørklund Holven, University of Oslo
- Stine Marie Ulven, University of Oslo
- Per Ole Iversen, University of Oslo
- Denis Grant, University of Toronto, Canada
- Tim Zacharewski, Michigan State University
- Michael Cohen, Oregon Health & Science University
- Jan Vondracek, Czech Academy of Sciences
- Zilvinas Dambrauskas and Antanas Gulbinas, Lithuanian University of Health Sciences
- Toivo Maimets, University of Tartu
- Kristaps Jaudzems, Latvian Institute of Organic Synthesis
- Chiara Gorrini, University of Leeds
Publications