Mikael Altun
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
- Journal article: RESULTS IN ENGINEERING. 2025;26:105570Perez-Diaz S; Leon JG; Lopez-Ortiz S; Mandic M; Altun M; Rundqvist H; Gustafsson T; Fernandez-Gonzalo R
- Article: JOURNAL OF BIOLOGICAL CHEMISTRY. 2025;301(4):108361Pires MJ; Alam S; Lovric A; Fabbrizi E; Rotili D; Altun M; Valerie NCK
- Article: NATURE COMMUNICATIONS. 2024;15(1):10347Valerie NCK; Sanjiv K; Mortusewicz O; Zhang SM; Alam S; Pires MJ; Stigsdotter H; Rasti A; Langelier M-F; Rehling D; Throup A; Purewal-Sidhu O; Desroses M; Onireti J; Wakchaure P; Almloef I; Bostrom J; Bevc L; Benzi G; Stenmark P; Pascal JM; Helleday T; Page BDG; Altun M
- Article: JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE. 2024;15(5):2143-2155Tarum J; Ball G; Gustafsson T; Altun M; Santos L
- Article: BIOLOGY-BASEL. 2023;12(9):1177Gronholdtklein M; Gorzi A; Wang L; Edstrom E; Rullman E; Altun M; Ulfhake B
- Article: COMMUNICATIONS BIOLOGY. 2022;5(1):1121Lovric A; Rassolie A; Alam S; Mandic M; Saini A; Altun M; Fernandez-Gonzalo R; Gustafsson T; Rullman E
- Article: CELL DEATH & DISEASE. 2021;12(10):914Giovannucci TA; Salomons FA; Haraldsson M; Elfman LHM; Wickstroem M; Young P; Lundbaeck T; Eirich J; Altun M; Jafari R; Gustavsson A-L; Johnsen JI; Dantuma NP
- Article: SCIENCE ADVANCES. 2021;7(32):eabf7561Kanellis DC; Espinoza JA; Zisi A; Sakkas E; Bartkova J; Katsori A-M; Bostrom J; Dyrskjot L; Broholm H; Altun M; Elsasser SJ; Lindstrom MS; Bartek J
- Article: MOVEMENT DISORDERS. 2021;36(5):1137-1146Feyder M; Plewnia C; Lieberman OJ; Spigolon G; Piccin A; Urbina L; Dehay B; Li Q; Nilsson P; Altun M; Santini E; Sulzer D; Bezard E; Borgkvist A; Fisone G
- Article: NUCLEIC ACIDS RESEARCH. 2020;48(21):12234-12251Visnes T; Benitez-Buelga C; Cazares-Korner A; Sanjiv K; Hanna BMF; Mortusewicz O; Rajagopal V; Albers JJ; Hagey DW; Bekkhus T; Eshtad S; Baquero JM; Masuyer G; Wallner O; Muller S; Pham T; Gokturk C; Rasti A; Suman S; Torres-Ruiz R; Sarno A; Wiita E; Homan EJ; Karsten S; Marimuthu K; Michel M; Koolmeister T; Scobie M; Loseva O; Almlof I; Unterlass JE; Pettke A; Bostrom J; Pandey M; Gad H; Herr P; Jemth A-S; El Andaloussi S; Kalderen C; Rodriguez-Perales S; Benitez J; Krokan HE; Altun M; Stenmark P; Berglund UW; Helleday T
- Article: NATURE CHEMICAL BIOLOGY. 2020;16(10):1120-1128Zhang SM; Desroses M; Hagenkort A; Valerie NCK; Rehling D; Carter M; Wallner O; Koolmeister T; Throup A; Jemth A-S; Almlof I; Loseva O; Lundback T; Axelsson H; Regmi S; Sarno A; Kraemer A; Pudelko L; Brautigam L; Rasti A; Gottmann M; Wiita E; Kutzner J; Schaller T; Kalderen C; Cazares-Korner A; Page BDG; Krimpenfort R; Eshtad S; Altun M; Rudd SG; Knapp S; Scobie M; Homan EJ; Berglund UW; Stenmark P; Helleday T
- Article: MOLECULAR & CELLULAR PROTEOMICS. 2020;19(4):608-623Herr P; Bostrom J; Rullman E; Rudd SG; Vesterlund M; Lehtio J; Helleday T; Maddalo G; Altun M
- Article: ACTA PHYSIOLOGICA. 2019;227(3):e13335Gronholdt-Klein M; Altun M; Becklen M; Kahm ED; Fahlstrom A; Rullman E; Ulfhake B
- Article: ENDOCRINE CONNECTIONS. 2019;8(7):1070-1081Saini A; Bjorkhem-Bergman L; Bostrom J; Lilja M; Melin M; Olsson K; Ekstrom L; Bergman P; Altun M; Rullman E; Gustafsson T
- Journal article: CANCER RESEARCH. 2019;79(13_Supplement):105Sanjiv K; gad H; Rudd SG; Mortusewicz O; Stolz A; Amaral N; Brautigham L; Pudelko L; Kaldéren C; Jemth A-S; Almlöf I; Visnes T; Schultz N; Boström J; Montano1 JMC; Hagenkort A; Groth P; Gokturk C; Koolmeister T; Wakchaure P; Homan E; Altun M; Ström C; Scobie M; Bastians H; Berglund UW; Helleday T
- Article: SCIENCE. 2018;362(6416):834-839Visnes T; Cazares-Korner A; Hao W; Wallner O; Masuyer G; Loseva O; Mortusewicz O; Wiita E; Sarno A; Manoilov A; Astorga-Wells J; Jemth A-S; Pan L; Sanjiv K; Karsten S; Gokturk C; Grube M; Homan EJ; Hanna BMF; Paulin CBJ; Pham T; Rasti A; Berglund UW; von Nicolai C; Benitez-Buelga C; Koolmeister T; Ivanic D; Iliev P; Scobie M; Krokan HE; Baranczewski P; Artursson P; Altun M; Jensen AJ; Kalderen C; Ba X; Zubarev RA; Stenmark P; Boldogh I; Helleday T
- Article: SCIENTIFIC REPORTS. 2018;8(1):11202Heshmati Y; Kharazi S; Turkoz G; Chang D; Dolatabadi EK; Bostrom J; Krstic A; Boukoura T; Wagner E; Kadri N; Mansson R; Altun M; Qian H; Walfridsson J
- Article: HAEMATOLOGICA. 2018;103(7):1169-1181The chromatin-remodeling factor CHD4 is required for maintenance of childhood acute myeloid leukemiaHeshmati Y; Turkoz G; Harisankar A; Kharazi S; Bostrom J; Dolatabadi EK; Krstic A; Chang D; Mansson R; Altun M; Qian H; Walfridsson J
- Article: MOLECULAR SYSTEMS BIOLOGY. 2018;14(3):e7858Azimi A; Caramuta S; Seashore-Ludlow B; Bostrom J; Robinson JL; Edfors F; Tuominen R; Kemper K; Krijgsman O; Peeper DS; Nielsen J; Hansson J; Brage SE; Altun M; Uhlen M; Maddalo G
- Article: PLOS ONE. 2017;12(12):e0188772Bostrom J; Sramkova Z; Salasova A; Johard H; Mahdessian D; Fedr R; Marks C; Medalova J; Soucek K; Lundberg E; Linnarsson S; Bryja V; Sekyrova P; Altun M; Andang M
- Article: ONCOGENESIS. 2016;5(12):e275Eshtad S; Mavajian Z; Rudd SG; Visnes T; Bostrom J; Altun M; Helleday T
- Article: CELL REPORTS. 2016;14(2):298-309Sanjiv K; Hagenkort A; Calderon-Montano JM; Koolmeister T; Reaper PM; Mortusewicz O; Jacques SA; Kuiper RV; Schultz N; Scobie M; Charlton PA; Pollard JR; Berglund UW; Altun M; Helleday T
- Article: PLOS ONE. 2015;10(1):e0115344Altun M; Walter TS; Kramer HB; Herr P; Iphoefer A; Bostrom J; David Y; Komsany A; Ternette N; Navon A; Stuart DI; Ren J; Kessler BM
- Article: NATURE. 2014;508(7495):215-221Gad H; Koolmeister T; Jemth A-S; Eshtad S; Jacques SA; Strom CE; Svensson LM; Schultz N; Lundback T; Einarsdottir BO; Saleh A; Gokturk C; Baranczewski P; Svensson R; Berntsson RP-A; Gustafsson R; Stromberg K; Sanjiv K; Jacques-Cordonnier M-C; Desroses M; Gustavsson A-L; Olofsson R; Johansson F; Homan EJ; Loseva O; Brautigam L; Johansson L; Hoglund A; Hagenkort A; Pham T; Altun M; Gaugaz FZ; Vikingsson S; Evers B; Henriksson M; Vallin KSA; Wallner OA; Hammarstrom LGJ; Wiita E; Almlof I; Kalderen C; Axelsson H; Djureinovic T; Puigvert JC; Haggblad M; Jeppsson F; Martens U; Lundin C; Lundgren B; Granelli I; Jensen AJ; Artursson P; Nilsson JA; Stenmark P; Scobie M; Berglund UW; Helleday T
- Article: CHEMISTRY AND BIOLOGY. 2013;20(12):1447-1455McGouran JF; Gaertner SR; Altun M; Kramer HB; Kessler BM
- Article: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 2013;433(4):390-395Velasco K; Zhao B; Callegari S; Altun M; Liu H; Hassink G; Masucci MG; Lindsten K
- Article: CANCER CELL. 2012;22(3):345-358Chauhan D; Tian Z; Nicholson B; Kumar KGS; Zhou B; Carrasco R; McDermott JL; Leach CA; Fulcinniti M; Kodrasov MP; Weinstock J; Kingsbury WD; Hideshima T; Shah PK; Minvielle S; Altun M; Kessler BM; Orlowski R; Richardson P; Munshi N; Anderson KC
- Article: ORGANIC & BIOMOLECULAR CHEMISTRY. 2012;10(17):3379-3383McGouran JF; Kramer HB; Mackeen MM; di Gleria K; Altun M; Kessler BM
- Article: JOURNAL OF BIOLOGICAL CHEMISTRY. 2012;287(3):1962-1969Ubiquitin-specific Protease 19 (USP19) Regulates Hypoxia-inducible Factor 1α (HIF-1α) during HypoxiaAltun M; Zhao B; Velasco K; Liu H; Hassink G; Paschke J; Pereira T; Lindsten K
- Article: CHEMISTRY AND BIOLOGY. 2011;18(11):1401-1412Altun M; Kramer HB; Willems LI; McDermott JL; Leach CA; Goldenberg SJ; Kumar KGS; Konietzny R; Fischer R; Kogan E; Mackeen MM; McGouran J; Khoronenkova SV; Parsons JL; Dianov GL; Nicholson B; Kessler BM
- Article: VIROLOGY JOURNAL. 2011;8(1):442Ternette N; Wright C; Kramer HB; Altun M; Kessler BM
- Article: CHEMISTRY AND BIOLOGY. 2011;18(5):642-654Rotili D; Altun M; Kawamura A; Wolf A; Fischer R; Leung IKH; Mackeen MM; Tian Y-M; Ratcliffe PJ; Mai A; Kessler BM; Schofield CJ
- Article: CHEMICAL COMMUNICATIONS. 2011;47(5):1488-1490Rotili D; Altun M; Hamed RB; Loenarz C; Thalhammer A; Hopkinson RJ; Tian Y-M; Ratcliffe PJ; Mai A; Kessler BM; Schofield CJ
- Article: JOURNAL OF BIOLOGICAL CHEMISTRY. 2010;285(51):39597-39608Altun M; Besche HC; Overkleeft HS; Piccirillo R; Edelmann MJ; Kessler BM; Goldberg AL; Ulfhake B
- Article: FEBS JOURNAL. 2010;277(11):2515-2530Edelmann MJ; Kramer HB; Altun M; Kessler BM
- Article: EMBO REPORTS. 2009;10(7):755-761Hassink GC; Zhao B; Sompallae R; Altun M; Gastaldello S; Zinin NV; Masucci MG; Lindsten K
- Article: BIOCHEMICAL JOURNAL. 2009;418(2):379-390Edelmann MJ; Iphofer A; Akutsu M; Altun M; di Gleria K; Kramer HB; Fiebiger E; Dhe-Paganon S; Kessler BM
- Article: PHYSIOLOGY & BEHAVIOR. 2007;92(5):911-923Altun M; Bergman E; Edstrom E; Johnson H; Ulfhake B
- Article: PHYSIOLOGY & BEHAVIOR. 2007;92(1-2):129-135Edstrom E; Altun M; Bergman E; Johnson H; Kullberg S; Ramirez-Leon V; Ulfhake B
- Article: MUSCLE & NERVE. 2007;36(2):223-233Altun M; Edstrom E; Spooner E; Flores-Moralez A; Bergman E; Tollet-Egnell P; Norstedt G; Kessler BM; Ulfhake B
- Article: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES. 2006;61(7):663-674Edstrom E; Altun M; Hagglund M; Ulfhake B
- Article: CANCER RESEARCH. 2005;65(17):7896-7901Altun M; Galardy PJ; Shringarpure R; Hideshima T; LeBlanc R; Anderson KC; Ploegh HL; Kessler BM
- Article: AGING CELL. 2003;2(1):47-57Jiang XG; Edstrom E; Altun M; Ulfhake B
- Article: CHEMISTRY AND BIOLOGY. 2001;8(9):913-929Kessler BM; Tortorella D; Altun M; Kisselev AF; Fiebiger E; Hekking BG; Ploegh HL; Overkleeft HS
- Article: JOURNAL OF NEUROSCIENCE METHODS. 2001;108(1):19-24Altun M; Bergman E; Ulfhake B
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All other publications
- Preprint: BIORXIV. 2025Alam S; Pires MJ; Tidestav G; Jemth A-S; Eklund J; Klingegård F; Caraballo R; Gaetani M; Rotilli D; van den Elzen S; van Berkum E; Wallner O; Malmström J; Arvidsson PI; Valerie NCK; Altun M
- Preprint: BIORXIV. 2025Shu H; Sharm S; Alam S; Frank L; Tampere M; van Kuilenburg ABP; Valerie NCK; Altun M; Chabes A; Rudd SG; Zhang SM
- Preprint: BIORXIV. 2024Pires M; Lovric A; Alam S; Fabbrizi E; Rotili D; Altun M; Altun M; Valerie NCK
- Preprint: PREPRINTS.ORG. 2023GrönholdtKlein M; Gorzi A; Wang L; Edström E; Rullman E; Altun M; Ulfhake B
- Preprint: BIORXIV. 2022Valerie NCK; Sanjiv K; Mortusewicz O; Zhang SM; Alam S; Pires M; Stigsdotter H; Rasti A; Langelier M-F; Langelier M-F; Rehling D; Throup A; Desroses M; Onireti J; Wakchaure P; Almlöf I; Boström J; Bevc L; Benzi G; Stenmark P; Pascal J; Helleday T; Page BDG; Altun M
- Preprint: BIORXIV. 2022Heshmati Y; Türköz G; Dimitriou M; Harisankar A; Boström J; Cai H; Kadri N; Altun M; Qian H; Walfridsson J
- Preprint: BIORXIV. 2021Giovannucci T; Salomons F; Haraldsson M; Elfman L; Wickström M; Young P; Lundbäck T; Eirich J; Altun M; Jafari R; Gustavsson A-L; Johnsen JI; Dantuma N
- Preprint: SSRN ELECTRONIC JOURNAL. 2020Giovannucci TA; Salomons FA; Martin Haraldsson M; Elfman LMH; Wickström M; Young P; Lundbäck T; Eirich J; Altun M; Jafari R; Gustavsson A-L; Johnsen JI; Dantuma N
- Meeting abstract: CANCER RESEARCH. 2019;79(13):105Sanjiv K; Gad H; Rudd SG; Mortusewicz O; Stolz A; Amaral N; Brautigham L; Pudelko L; Kalderen C; Jemth A-S; Almlof I; Visnes T; Schultz N; Bostrom J; Montano JMC; Hagenkort A; Groth P; Gokturk C; Koolmeister T; Wakchaure P; Homan E; Altun M; Strom C; Scobie M; Bastians H; Berglund UW; Helleday T
- Conference publication: JOURNAL OF VASCULAR RESEARCH. 2019;56:86Nwadozi E; Fawzy A; Hansson B; Bostrom J; Altun M; Gustafsson T; Haas T
- Editorial comment: CELL CHEMICAL BIOLOGY. 2017;24(12):1429-1431Desroses M; Altun M
- Corrigendum: NATURE. 2017;544(7651):508Gad H; Koolmeister T; Jemth A-S; Eshtad S; Jacques SA; Strom CE; Svensson LM; Schultz N; Lundback T; Einarsdottir BO; Saleh A; Gokturk C; Baranczewski P; Svensson R; Berntsson RP-A; Gustafsson R; Stromberg K; Sanjiv K; Jacques-Cordonnier M-C; Desroses M; Gustavsson A-L; Olofsson R; Johansson F; Homan EJ; Loseva O; Brautigam L; Johansson L; Hoglund A; Hagenkort A; Pham T; Altun M; Gaugaz FZ; Vikingsson S; Evers B; Henriksson M; Vallin KSA; Wallner OA; Hammarstrom LGJ; Wiita E; Almlof I; Kalderen C; Axelsson H; Djureinovic T; Puigvert JC; Haggblad M; Jeppsson F; Martens U; Lundin C; Lundgren B; Granelli I; Jensen AJ; Artursson P; Nilsson JA; Stenmark P; Scobie M; Berglund UW; Helleday T
- Corrigendum: CELL REPORTS. 2016;17(12):3407-3416Sanjiv K; Hagenkort A; Calderon-Montano JM; Koolmeister T; Reaper PM; Mortusewicz O; Jacques SA; Kuiper RV; Schultz N; Scobie M; Charlton PA; Pollard JR; Berglund UW; Altun M; Helleday T
- Review: BIOCHIMICA ET BIOPHYSICA ACTA: INTERNATIONAL JOURNAL OF BIOCHEMISTRY AND BIOPHYSICS. 2012;1823(11):2029-2037Kramer HB; Nicholson B; Kessler BM; Altun M
- Book chapter: SENESCENCE. 2012;p.Altun M; Grönholdt-Klein M; Wang L; Ulfhake B
- Doctoral thesis: 2007Altun M
Grants
- Swedish Research Council1 January 2024 - 31 December 2026The 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 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 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