Mikael Altun
Researcher | Docent
E-mail: mikael.altun@ki.se
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). While conventional small molecules must block the aberrant activity of a target protein, PROTACs serve to completely eliminate the protein by directing it to the proteasome for degradation by the ubiquitin system. Since PROTACs eliminate the target protein by degradation, similar to functional genetics 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 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 group leader 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/
Articles
- Article: NATURE COMMUNICATIONS. 2024;15(1):10347
- Article: JOURNAL OF CACHEXIA, SARCOPENIA AND MUSCLE. 2024;15(5):2143-2155
- Article: BIOLOGY. 2023;12(9):1177
- Article: COMMUNICATIONS BIOLOGY. 2022;5(1):1121
- Article: CELL DEATH AND DISEASE. 2021;12(10):914
- Article: SCIENCE ADVANCES. 2021;7(32):eabf7561
- Article: MOVEMENT DISORDERS. 2021;36(5):1137-1146
- Article: NUCLEIC ACIDS RESEARCH (NAR). 2020;48(21):12234-12251
- Article: NATURE CHEMICAL BIOLOGY. 2020;16(10):1120-1128
- Article: MOLECULAR & CELLULAR PROTEOMICS. 2020;19(4):608-623
- Article: ACTA PHYSIOLOGICA. 2019;227(3):e13335
- Article: ENDOCRINE CONNECTIONS. 2019;8(7):1070-1081
- Journal article: CANCER RESEARCH. 2019;79(13_Supplement):105
- Article: SCIENCE. 2018;362(6416):834-839
- Article: SCIENTIFIC REPORTS. 2018;8(1):11202
- Article: HAEMATOLOGICA. 2018;103(7):1169-1181
- Article: MOLECULAR SYSTEMS BIOLOGY. 2018;14(3):e7858
- Article: PLOS ONE. 2017;12(12):e0188772
- Article: ONCOGENESIS. 2016;5(12):e275
- Article: CELL REPORTS. 2016;14(2):298-309
- Article: PLOS ONE. 2015;10(1):e0115344
- Article: NATURE. 2014;508(7495):215-221
- Article: CHEMISTRY AND BIOLOGY. 2013;20(12):1447-1455
- Article: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 2013;433(4):390-395
- Article: CANCER CELL. 2012;22(3):345-358
- Article: ORGANIC AND BIOMOLECULAR CHEMISTRY. 2012;10(17):3379-3383
- Article: JOURNAL OF BIOLOGICAL CHEMISTRY. 2012;287(3):1962-1969
- Article: CHEMISTRY AND BIOLOGY. 2011;18(11):1401-1412
- Article: CHEMISTRY AND BIOLOGY. 2011;18(5):642-654
- Article: CHEMICAL COMMUNICATIONS. 2011;47(5):1488-1490
- Article: JOURNAL OF BIOLOGICAL CHEMISTRY. 2010;285(51):39597-39608
- Article: THE FEBS JOURNAL. 2010;277(11):2515-2530
- Article: EMBO REPORTS. 2009;10(7):755-761
- Article: BIOCHEMICAL JOURNAL. 2009;418(2):379-390
- Article: PHYSIOLOGY AND BEHAVIOR. 2007;92(5):911-923
- Article: PHYSIOLOGY AND BEHAVIOR. 2007;92(1-2):129-135
- Article: MUSCLE AND NERVE. 2007;36(2):223-233
- Article: THE JOURNALS OF GERONTOLOGY. SERIES A, BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. 2006;61(7):663-674
- Article: CANCER RESEARCH. 2005;65(17):7896-7901
- Article: AGING CELL. 2003;2(1):47-57
- Article: CHEMISTRY AND BIOLOGY. 2001;8(9):913-929
- Article: JOURNAL OF NEUROSCIENCE METHODS. 2001;108(1):19-24
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All other publications
- Preprint: BIORXIV. 2024
- Preprint: PREPRINTS.ORG. 2023
- Preprint: BIORXIV. 2022
- Preprint: BIORXIV. 2022
- Preprint: BIORXIV. 2021
- Preprint: SSRN ELECTRONIC JOURNAL. 2020
- Meeting abstract: CANCER RESEARCH. 2019;79(13):105
- Conference publication: JOURNAL OF VASCULAR RESEARCH. 2019;56:86
- Editorial comment: CELL CHEMICAL BIOLOGY. 2017;24(12):1429-1431
- Corrigendum: NATURE. 2017;544(7651):508
- Corrigendum: CELL REPORTS. 2016;17(12):3407-3416
- Review: BIOCHIMICA ET BIOPHYSICA ACTA: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND BIOPHYSICS. 2012;1823(11):2029-2037
- Book chapter: SENESCENCE. 2012;p.
- Thesis / dissertation: 2007
Grants
- Swedish Research Council1 January 2024 - 31 December 2026
- Cancer-specific targeted protein degradation through FBXO22Novo Nordisk Foundation1 February 2022 - 31 August 2023
- Swedish Research Council1 January 2021 - 31 December 2023
- Prevention of Protein Aggregations by Activation of Protein Degradation MechanismsHållsten Foundation1 January 2020
- CANCERPREVEuropean Commission Directorate-General for Research and Innovation1 December 2019 - 30 April 2024
- BIPODSciLifeLabs Sweden1 October 2018
- Exploring Deubiquitylating Enzyme for cancer therapyMEDIVIR1 January 2017
- Swedish Research Council1 January 2015 - 31 December 2018
- Research Associate/Assistant Professor in Medical Sciences at Karolinska InstitutetKarolinska Institutet1 January 2014 - 31 December 2017
- Start-up AwardStratNeuro karolinska Institutet1 January 2014
- Hållsten Academy FellowHållsten Foundation1 January 2014
- Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapiesJeansson Foundations1 January 2013 - 31 December 2015
- Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapiesÅhlen Foundation1 January 2013 - 31 December 2015
- Swedish Research Council1 January 2012 - 31 December 2014
- Targeting the deubiquitylating enzymes in the Nervous system for new insights and novel therapiesÅke-Wibergs Foundation1 January 2012 - 31 December 2015
- Swedish Research Council1 June 2011 - 31 May 2012
Employments
- Researcher, Department of Laboratory Medicine, Karolinska Institutet, 2018-
- Postdoctoral Researcher, Department of Cell and Molecular Biology, Karolinska Institute, 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
Supervisor
- Seher Alam, 2024
- Maria Joao Pires, 2020
- Johan Boström, Studying the Cell Cycle using Systems Biology and High Content Characterization of the Ubiquitin Proteasome System., https://openarchive.ki.se/xmlui/handle/10616/47323, 2014
- Daniela Papadia, Cellular and network mechanisms in neurodegenerative disorders : neurotoxicity and rescue strategies., https://openarchive.ki.se/xmlui/handle/10616/46338, 2014
- Saeed Eshtad, Targeting DNA repair Pathways for Cancer Therapy., https://openarchive.ki.se/xmlui/handle/10616/45467, 2012
- Michael Feyder, L-DOPA-induced signaling pathways and neuroepigenetic mechanisms in experimental parkinsonism and dyskinesia., https://openarchive.ki.se/xmlui/handle/10616/42273, 2012
- Bin Zhao, Functional studies of deubiquitinating enzymes., https://openarchive.ki.se/xmlui/handle/10616/41134, 2008
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 Institute, 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