Background and activities

Curriculum:

  • 2010-         CSO, APIM Therapeutics, Trondheim, Norway (part time)
  • 2003-    Professor, Faculty of Medicine and Health Sciences, Department of Clinical and Molecular medicine (IKOM), Norwegian University of Science and Technology (NTNU), Trondheim, Norway (main position).
  • Visiting scientist at Centre de Rescherche en Cancerologies de Marseille (CRCM), France (spring) and Department of Biology, University of Copenhagen, Denmark (fall), 2019.
  • Visiting scientist at Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, Baltimore, USA, 2003-2003.
  • Researcher/group leader, Department of Cancer Research, NTNU, after receiving a carrier grant from RCN on the project “Replication associated DNA repair”, 2002-2006.
  • Associated professor II, UNIGEN, Center for Molecular biology and Dept. of Cancer Research, University of Trondheim, UNIT (now NTNU), 1988-2002.
  • Postdoctoral fellow in DNA repair at UNIGEN, Center for Molecular biology, UNIT (now NTNU), 1994-2001.
  • PhD (Dr.ing) in innate immunity at Department of Biotechnology in collaborations with the Department of Cancer Research, The Norwegian Institute of Technology, NTH/UNIT (now NTNU), 1994.
  • MSc (Siv.ing) from the Department of Biotechnology, NTH (now NTNU), 1988.

 

Proteins in the DNA sliding clamp family are structurally conserved essential proteins in all three kingdoms of life. Their role in DNA replication and repair is well known, but the recently discovered roles of the eukaryote DNA sliding clamp PCNA in regulation of cellular signaling, cellular metabolism and apoptosis indicate that this family of proteins has additional functions of importance for cellular stress responses. This highlights the clamp family as promising drug targets.

Based on the scientific discovery of the novel PCNA interaction motif, APIM, Otterlei founded the NTNU spin-off company APIM Therapeutics in 2009, and has since then been in charge of the development of a peptide drug containing the APIM sequence for use in cancer therapy as a part time CSO in APIM Therapeutics (https://www.apimtherapeutics.com/). Clinical trial (phase I) started fall 2018 and will be closed within the summer/early fall of 2020. The drug is well tolerated, and further Phase II studies are planned.

Central studies for understanding of the processes regulated by APIM-PCNA interactions and therefore important for understanding the mode of action of the APIM-peptide drug are:

  • Basic research exploring the roles of the APIM – PCNA interactions in the regulation of DNA repair (Gilljam et al., 2009 (PMID 19736315) and 2012 (PMID 23152873)), DNA damage tolerance  (Ræder et al., 2018 (PMID 30597836) and Seelinger and Otterlei, 2019 (PMID 31973093)) and cellular stress signaling (Olaisen et al, 2015 (PMID 25797046) and 2018 (PMID 29988559)
  • In vivo anti-cancer effects (animal models) and cellular effects of targeting PCNA with peptides containing APIM (Gederaas et al., 2014 (PMID 25500092), Søgaard et al., 2018 (PMID 29545934) and (PMID 30197755), Søgaard et al., 2019 (PMID 31921382), Røst et al., 2020 (doi.org/10.1101/2020.04.29.067512).

    • During studies of the peptide as an anti-cancer drug, an infection in one of the cell cultures lead to the discovery of the peptide’s antibacterial activity. This activity is recently shown to be linked its interaction with the beta-clamp (Nedal et al. 2020 (PMID 32347931).

    The research group’s current focus is to further explore peptides targeting the bacterial DNA sliding clamp for anti-bacterial activities.

    • Select a clinical indication for further development
    • Explore the beta-clamp’s role outside DNA replication, i.e. elucidate the involvement in regulation of cellular signaling and metabolism
    • Explore the interaction between the APIM-peptide and its target.

    Increase the understanding of the complex roles of the DNA clamp in prokaryotes is important for development of drugs targeting the beta-clamp.

    The project “Targeting AMR by inhibition of bacterial stress responses”, TAMiR, is one out of four AMR related projects in Norway funded by the Trond Mohn Foundation (TMS) (see: https://mohnfoundation.no/amr-prosjekter/). 

     

     

    Scientific, academic and artistic work

    A selection of recent journal publications, artistic productions, books, including book and report excerpts. See all publications in the database

    Journal publications