Mikael Altun

Mikael Altun

Researcher | Docent
Visiting address: Alfred Nobels allé 8, 14152 Huddinge
Postal address: H5 Laboratoriemedicin, H5 Klin Fysiologi, 141 52 Huddinge

Research

  • The ubiquitin-proteasome system (UPS) plays a central role in most cellular processes. Recent data suggest that the UPS plays a role beyond the well-known housekeeping function of protein turnover and highlight that more needs to be done to understand the complex nature of the UPS and its functions in the cell. We are studying the UPS starting from basic cellular functions and working to understand its involvement in human diseases ranging from muscle atrophies to cancer. In addition, our efforts are focused on developing new molecular, chemical and biophysical technologies to gain insights into complex cellular processes.

         One focus of our work with translational potential is the “hijacking" of the UPS for targeted protein degradation with small molecules that have the potential to develop new therapeutic strategies. With this approach, we hope to unravel the “untreatable" proteome and develop a better strategy to combat diseases where therapeutic options are limited by conventional drug discovery approaches. One such targeted degradation tactic involves bifunctional molecules that recruit UPS components to degrade a target protein – better known as PROTACs (PROteolysis-TArgeting Chimeras). Another is molecular glue degraders that similarly recruit neosubstrates to E3 ligases for degradation.

        While conventional small molecules must block the aberrant activity of a target protein, PROTACs and molecular glue degraders serve to completely eliminate the protein by directing it to the proteasome for degradation by the ubiquitin system. Since both eliminate the target protein by degradation, similar to functional genetic approaches (e.g. RNAi and CRISPR/Cas9), we can correlate molecular changes and predict cellular phenotypes much better – something that conventional therapeutics usually cannot fully recapitulate. Since conventional small molecules are always subject to off-target effects, PROTACs and molecular glue degraders can greatly improve the predictability of gene function studies by mimicking the effects observed in conventional genetic ablation studies.

    Another goal is to develop biotechnologies to answer important scientific questions that require a cellular context, such as monitoring cellular protein-ligand interactions. This research is led by my colleague Nicholas Valerie (staff.ki.se/people/nicval). Dr. Altun is a Scientific Platform Director at the Science for Life Laboratory (SciLifeLab) in Stockholm, an important hub for Sweden’s national life science infrastructures (https://www.scilifelab.se/researchers/mikael-altun/ [1]).


    [1] https://www.scilifelab.se/researchers/mikael-altun/

    Acknowledgements:

    The lab will be forever grateful to the Hållsten family for supporting us from the beginning and always believing in what we do.

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2024 - 31 December 2026
    The increasing number of older people being disabled by aging threatens the sustainability of the health systems. Thus, there is an urgent need to counteract aging-induced disabling conditions as muscle wasting. The proposed project is based on longitudinal observations across the lifespan of adults in a cohort born in 1956/58 (SPAF-1958). This cohort has been followed from age 16 to 63 years using objective measures of physical performance, physical activity, and lifestyle variables at four time points, available and skeletal muscle biopsies (at 27 and 63 years) and blood samples (at ages 52 and 63 years). The SPAF-1958 cohort provides a unique opportunity to detect longitudinal changes, i.e., individual trajectories, thus elucidating the preclinical and clinical course of sarcopenia and revealing underlying factors at the individual level. In the proposed study, measurements will be repeated at age 67 years since it is reasonable to shorten the intervals between follow-ups as the effects of aging increase with time. A unique feature of the current study as individuals enter early-aging, is the combination of analyses of neurogenic components. This includes examination of motor and sensory nerve conduction, number of motor units combined with measurements of muscle mass and quality by MRI and muscle tissue morphology and gene expression from biopsies. The current study may also add information about biological aging biomarkers in blood and individual genetic makeup.
  • Cancer-specific targeted protein degradation through FBXO22
    Novo Nordisk Foundation
    1 February 2022 - 31 August 2023
  • Prevention of Protein Aggregations by Activation of Protein Degradation Mechanisms
    Hållsten Foundation
    1 January 2020
  • CANCERPREV
    European Commission Directorate-General for Research and Innovation
    1 December 2019 - 30 April 2024
  • BIPOD
    SciLifeLabs Sweden
    1 October 2018
  • Exploring Deubiquitylating Enzyme for cancer therapy
    MEDIVIR
    1 January 2017
  • Research Associate/Assistant Professor in Medical Sciences at Karolinska Institutet
    Karolinska Institutet
    1 January 2014 - 31 December 2017
  • Start-up Award
    StratNeuro karolinska Institutet
    1 January 2014
  • Hållsten Academy Fellow
    Hållsten Foundation
    1 January 2014
  • Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapies
    Jeansson Foundations
    1 January 2013 - 31 December 2015
  • Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapies
    Åhlen Foundation
    1 January 2013 - 31 December 2015
  • Swedish Research Council
    1 January 2012 - 31 December 2014
  • Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapies
    Åke-Wibergs Foundation
    1 January 2012 - 31 December 2015
  • Swedish Research Council
    1 June 2011 - 31 May 2012

Employments

  • Researcher, Department of Laboratory Medicine, Karolinska Institutet, 2018-
  • Postdoctoral Researcher, Department of Cell and Molecular Biology, Karolinska Institutet, 2008-2009

Degrees and Education

  • Docent, Karolinska Institutet, 2020
  • Doctor Of Philosophy, Department of neuroscience, Karolinska Institutet, 2007
  • Master Of Medical Science, Karolinska Institutet, 2003

Visiting research fellowships

  • Utilizing mass-spectrometry and Chemical Biology to unravel the functions of deubiqutinating enzymes with a special focus on the Otubains, University of Oxford, 2009-2011

Thesis evaluation

  • Hanzhao Zhang, Examination board member, Departement of Immunology, genetics and pathology, Uppsala University, 2024
  • Johannes Gubat, Examination board member, Department of Biomedical and Clinical Sciences, Linköping University, 2024
  • Mirko Mandic, Defence chairperson, Laboratory Medicine, Karolinska Institutet, Blood volume expansion following supramaximal exercise : occurrence and contribution to maximal oxygen uptake, https://openarchive.ki.se/xmlui/handle/10616/48423, 2023
  • Kristijonas Zemaitis, Examination board member, Department of Laboratory Medicine and Lund Stem Cell Center, Lund University, Unravelling mechanisms of hematopoietic stem cell expansion, 2022

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