Basic research into the molecular and cellular mechanisms of selective autophagy and cell signaling and how these affect neurodegenerative diseases and cancers. Cells remove damaged, worn-out or surplus proteins, lipids and organelles through selective autophagy. When this process goes wrong, it leads to conditions such as neurodegenerative diseases and cancers. The selective removal of damaged or surplus mitochondria through autophagy or mitophagy is crucial for maintaining cellular homeostasis and prevent diseases. We discovered that the proteins NIPSNAP1/2 act as ‘Eat-me’ signals on mitochondria that determine their removal. We have also discovered that the protein SAMM50 act as receptor to remove worn-out or surplus mitochondrial parts through piecemeal mitophagy.

Several drugs used to treat cancer tend to damage the mitochondria in other to induce apoptosis and kill cancer cells. We have now discovered that cancer cells are able to turn on mitophagy quickly to removed damaged mitochondrial upon treatment, and this process contribute greatly to drug resistance. We are now studying the mechanism of drug-induced mitophagy in other to understand how we can target this pathway to allow for cancer drugs to be more effective.

Basic research into the cellular- and molecular mechanisms of selective autophagy and cell signaling relevant for cancer, neurodegenerative diseases, aging, inflammation and host defense against intracellular pathogens. Terje and his group made a major breakthrough in our understanding of selective autophagy by discovering the first selective autophagy receptor p62/SQSTM1 and elucidated how specificity in cargo selection (waste disposal) could be achieved and how autophagy receptors could connect the cargo (waste) to the forming autophagosome. Some main discoveries by Terje and co-workers in the Autophagy Research Group are:

• Discovered the first selective autophagy receptors p62/SQSTM1 and NBR1

• Showed that the selective autophagy receptors bound to cargo and to Atg8 family proteins

• Identified the LIR (LC3 Interacting Region) motif mediating the interaction in the majority of Atg8 interacting proteins

• Discovered p62 formed protein bodies inside cells that are degraded by autophagy

• Developed a novel tandem tag fluorescent protein assay to monitor autophagic flux

• Described the positive feedback loop regulation between p62 and NRF2

• Found NBR1 as the selective autophagy receptor in plants

• Discovered NBR1 acting as a pexophagy receptor

• Discovered the first Golgiphagy receptor, CALCOCO1, also acting in ERphagy

• Showed Atg8 family proteins to act as membrane-bound scaffolds for autophagy core machinery proteins including the ULK1/2 complexes, the PI3K class III complex and ATG4 proteins.

• Showed NIPSNAP1 and NIPSNAP2 to act as "Eat Me" signals for Mitophagy

• Discovered that FKBP8 can act as a mitophagy receptor and that SAMM50 is involved in basal and OXPHOS-induced mitophagy

• Found the inflammation repressor TNIP1/ABIN-1 to be degraded by autophagy following TBK1 activation.
• Discovered MORG1 as a new negative regulator of mTORC1 allowing basal selective autophagy in nutrient rich conditions.

Keywords: Selective autophagy receptors, ATG8 family proteins, LIR motifs, aggrephagy, mitophagy, ER-phagy, Golgiphagy

The main goal of the research group (including Trond) is to understand the molecular mechanisms utilized by cells to cope with stress, under normal conditions and in disease. The discovery of the first selective autophagy receptors in 2005 led the research into the autophagy field, and autophagy soon became their main interest. Autophagy was at that time considered a basically non-selective process and the pathological importance of autophagy was not fully realized. The identification of the first selective autophagy receptors coincided with an increased interest in autophagy research worldwide. The following research (including work by the autophagy research group) revealed the process to be highly selective. It soon became evident that reduced selective autophagy is associated with aging, and is implicated in several age-related pathologies, including neurodegenerative diseases, cancer, and inflammation. Our understanding of selective autophagy is now at a different level compared to 20 years ago, but several important knowledge gaps exist, and the remaining goal is to fill these gaps with new knowledge. 

My research focuses on the molecular mechanisms of autophagy, with a particular emphasis on the biogenesis and regulation of omegasomes—ER-derived membranes that initiate selective autophagy. I am particularly interested in how membrane remodeling events control autophagosome formation, expansion, and closure. We are also exploring how autophagy interfaces with ER dynamics, membrane shaping, and intracellular signaling, contributing to broader questions of organelle communication and stress adaptation.

A key goal of my work is to understand how selective autophagy contributes to cancer progression and therapy resistance. My group investigates how autophagy supports cancer cell survival during stress, particularly in the context of radiotherapy, and aims to identify molecular targets to sensitize cancer cells to treatment. We combine mechanistic cell biology with imaging, biochemistry, and genetic perturbation tools to dissect the spatial and temporal regulation of autophagy in cancer cells.