About me
PhD degree (Experimental Oncology) 2004, and Docent in Experimental Pathology obtained 2012 at Karolinska Institutet i Stockholm, Sweden (Assoc Prof equivalent/ or habiliation).
At present researcher at the Department of Medical Biochemistry and Biophysics, KI, SciLifeLab in Stockholm. Besides being involved research I am also active in teaching medical students (former DFM1, now known as BV2), foreign medical doctors aiming for license, and students at the Biomedicine program (course Biochemistry). I´m also supervising postdoctoral fellows, PhD students and master students. Several tasks in peer review, editorial board, and serving on expert panels.
Research description
We are specifically interested in molecular mechanisms underlying the regulation of ribosome biogenesis, how the cell senses errors in the complex process of ribosome biogenesis and how these processes in turn can be used in the development of novel anti-cancer therapies.
To investigate ribosome biogenesis and nucleolar structure, the team uses various microscopy technologies, ribosome profiling, rDNA assays, transcriptomics, translatomics, and proteomics. We also work a lot with small molecules and functional screens.
Main lines and interests of research:
1. Characterization of ribosome biogenesis regulatory proteins and potential role in cancer development, biomarker discovery for precision / personalized cancer medicine. 2. Regulation of ribosome biogenesis and protein synthesis in normal CNS cells and in glioma, including heterogeneity of ribosome in relation to glioma cellular diversity. 3. Targeting of ribosome biogenesis or mature ribosome function in cancer. 4. Functional studies of ribosomal proteins.
Selected references but for a more complete list search Pubmed: "Lindstrom MS" or ORCID.
Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET. Kanellis DC, Zisi A, Skrott Z, Lemmens B, Espinoza JA, Kosar M, Björkman A, Li X, Arampatzis S, Bartkova J, Andújar-Sánchez M, Fernandez-Capetillo O, Mistrik M, Lindström MS, Bartek J Cell Death Differ 2023 May;():
Small Molecule-mediated Disruption of Ribosome Biogenesis Synergizes With FGFR Inhibitors to Suppress Glioma Cell Growth. Zisi A, Kanellis DC, Moussaud S, Karlsson I, Carén H, Bräutigam L, Bartek J, Lindström MS Neuro Oncol 2022 Dec;():
Targeting Ribosome Biogenesis in Cancer: Lessons Learned and Way Forward. Zisi A, Bartek J, Lindström MS Cancers (Basel) 2022 Apr;14(9):2126
p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways. Lindström MS, Bartek J, Maya-Mendoza A Cell Death Differ 2022 May;29(5):972-982
The exon-junction complex helicase eIF4A3 controls cell fate via coordinated regulation of ribosome biogenesis and translational output. Kanellis DC, Espinoza JA, Zisi A, Sakkas E, Bartkova J, Katsori AM, Boström J, Dyrskjøt L, Broholm H, Altun M, Elsässer SJ, Lindström MS, Bartek J Sci Adv 2021 08;7(32):eabf7561
SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma. Guo M, Goudarzi KM, Abedi S, Pieber M, Sjöberg E, Behnan J, Zhang XM, Harris RA, Bartek J, Lindström MS, Nistér M, Hägerstrand D Oncogene 2021 08;40(32):5066-5080
Identification of functionally distinct and interacting cancer cell subpopulations from glioblastoma with intratumoral genetic heterogeneity. Guo M, van Vliet M, Zhao J, de Ståhl TD, Lindström MS, Cheng H, et al Neurooncol Adv 2020 ;2(1):vdaa061
Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds. Peuget S, Zhu J, Sanz G, Singh M, Gaetani M, Chen X, et al Cancer Res. 2020 Apr;80(7):1538-1550
The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity. Espinoza JA, Zisi A, Kanellis DC, Carreras-Puigvert J, Henriksson M, Hühn D, et al Cell Death Differ. 2020 02;27(2):773-789
Reduced Expression of PROX1 Transitions Glioblastoma Cells into a Mesenchymal Gene Expression Subtype. Goudarzi KM, Espinoza JA, Guo M, Bartek J, Nistér M, Lindström MS, et al Cancer Res. 2018 10;78(20):5901-5916
DNA damage-induced dynamic changes in abundance and cytosol-nuclear translocation of proteins involved in translational processes, metabolism, and autophagy. Bennetzen MV, Kosar M, Bunkenborg J, Payne MR, Bartkova J, Lindström MS, et al Cell Cycle 2018 ;17(17):2146-2163
Nucleolus as an emerging hub in maintenance of genome stability and cancer pathogenesis. Lindström MS, Jurada D, Bursac S, Orsolic I, Bartek J, Volarevic S Oncogene 2018 05;37(18):2351-2366
Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia. Jaako P, Ugale A, Wahlestedt M, Velasco-Hernandez T, Cammenga J, Lindström MS, et al Leukemia 2017 01;31(1):213-221
Role of ribosomal protein mutations in tumor development (Review). Goudarzi KM, Lindström MS Int. J. Oncol. 2016 Apr;48(4):1313-24
NPM1 histone chaperone is upregulated in glioblastoma to promote cell survival and maintain nucleolar shape. Holmberg Olausson K, Elsir T, Moazemi Goudarzi K, Nistér M, Lindström MS Sci Rep 2015 Nov;5():16495
Disruption of the 5S RNP-Mdm2 interaction significantly improves the erythroid defect in a mouse model for Diamond-Blackfan anemia. Jaako P, Debnath S, Olsson K, Zhang Y, Flygare J, Lindström MS, et al Leukemia 2015 Nov;29(11):2221-9
mTOR inhibitors blunt the p53 response to nucleolar stress by regulating RPL11 and MDM2 levels. Goudarzi KM, Nistér M, Lindström MS Cancer Biol. Ther. 2014 ;15(11):1499-514
Loss of nucleolar histone chaperone NPM1 triggers rearrangement of heterochromatin and synergizes with a deficiency in DNA methyltransferase DNMT3A to drive ribosomal DNA transcription. Holmberg Olausson K, Nistér M, Lindström MS J. Biol. Chem. 2014 Dec;289(50):34601-19
Targeting of MCL-1 kills MYC-driven mouse and human lymphomas even when they bear mutations in p53. Kelly GL, Grabow S, Glaser SP, Fitzsimmons L, Aubrey BJ, Okamoto T, et al Genes Dev. 2014 Jan;28(1):58-70
p53 -Dependent and -Independent Nucleolar Stress Responses. Holmberg Olausson K, Nistér M, Lindström MS Cells 2012 Oct;1(4):774-98
NPM1/B23: A Multifunctional Chaperone in Ribosome Biogenesis and Chromatin Remodeling. Lindström MS Biochem Res Int 2011 ;2011():195209
Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas. Elsir T, Eriksson A, Orrego A, Lindström MS, Nistér M J. Neuropathol. Exp. Neurol. 2010 Feb;69(2):129-38
An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction. Macias E, Jin A, Deisenroth C, Bhat K, Mao H, Lindström MS, et al Cancer Cell 2010 Sep;18(3):231-43
Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Itahana K, Mao H, Jin A, Itahana Y, Clegg HV, Lindström MS, et al Cancer Cell 2007 Oct;12(4):355-66
Cancer-associated mutations in the MDM2 zinc finger domain disrupt ribosomal protein interaction and attenuate MDM2-induced p53 degradation. Lindström MS, Jin A, Deisenroth C, White Wolf G, Zhang Y Mol. Cell. Biol. 2007 Feb;27(3):1056-68
Putting a finger on growth surveillance: insight into MDM2 zinc finger-ribosomal protein interactions. Lindström MS, Deisenroth C, Zhang Y Cell Cycle 2007 Feb;6(4):434-7
Essential role of the B23/NPM core domain in regulating ARF binding and B23 stability. Enomoto T, Lindström MS, Jin A, Ke H, Zhang Y J. Biol. Chem. 2006 Jul;281(27):18463-72
Predictive significance of the alterations of p16INK4A, p14ARF, p53, and proliferating cell nuclear antigen expression in the progression of cervical cancer. Wang JL, Zheng BY, Li XD, Angström T, Lindström MS, Wallin KL Clin. Cancer Res. 2004 Apr;10(7):2407-14
Myc and E2F1 induce p53 through p14ARF-independent mechanisms in human fibroblasts. Lindström MS, Wiman KG Oncogene 2003 Aug;22(32):4993-5005
Role of genetic and epigenetic changes in Burkitt lymphoma. Lindström MS, Wiman KG Semin. Cancer Biol. 2002 Oct;12(5):381-7
p14ARF homozygous deletion or MDM2 overexpression in Burkitt lymphoma lines carrying wild type p53. Lindström MS, Klangby U, Wiman KG Oncogene 2001 Apr;20(17):2171-7
MdmX binding to ARF affects Mdm2 protein stability and p53 transactivation. Jackson MW, Lindstrom MS, Berberich SJ J Biol Chem 2001 Jul;276(27):25336-41
Immunolocalization of human p14(ARF) to the granular component of the interphase nucleolus. Lindström MS, Klangby U, Inoue R, Pisa P, Wiman KG, Asker CE Exp. Cell Res. 2000 May;256(2):400-10
Referee
Around 50 papers per year on average for among others Oncogene, Nature, Nature Cell Biology, BioEssays, J Biol Chem, Mol Cell Biol, Proteins, J. of Clinical Investigation, Mol Cell, Intl. J of Cancer, Int J Mol Sciences, Cancer, Cancers, J Cytology & Histology, J Mol Biol, PLoS One, FEBS Letters, FEBS J, Future Oncology, Cell Proliferation, Biochem J, Nature Scientific Reports, Tumor Biology, Current Drug Targets, Cytotherapy, Nature Communications, J Cell Science, Cell Reports, Cell Cycle, Chemistry Biology (Cell press), Blood, Biomarkers, Cell Death Disease, EMBO J, EMBO Rep, JCI Insights, Cancer Cell, Frontiers Genetics, Pharmaceuticals, Biochem Soc Trans, Cells, Oncotarget, Int J of Dev Neuroscience, Cellular Physiology and Biochemistry, BMC Biotechnology, BMC Molecular Biology, Bioscience Reports, Cancer Res, Elife, J Cellular Physiology, Metabolites, EBiomedicine, ACS Chemical Biology, BBA Molecular Res, BioEssays, Communications Biol, and many others...
Teaching portfolio
Supervision of PhD students
Main supervisor:
Dr Kaveh Moazemi Goudarzi, PhD 2018-04-27 KI
Dr Asimina Zisi, PhD, 2022-10-28 KI
Co-supervisor:
Dr Tamador Elsir, PhD 2010-06-04 KI
Dr Inga Nazarenko, PhD 2011-09-30 KI
Dr Karl Holmberg-Olausson, PhD 2015-06-01 KI
Courses taken
a. Basic pedagogics for university lecturers GHPH09, 2009, KI ; b. Postgraduate supervisor training course, KI ; c. Leadership education “UGL”, KI
Teaching
Teaching at the Medical Students program (DFM1 course, biochemistry), around 600 hrs, including seminar leader and regular lectures, project examination, and correction of exams, and at the Biomedicine (Bachelor program) including seminar leader, PBL tutor, and lab supervisor in the oncology-tumor biology and cell biology courses. Over the years, lecturer to a number of graduate courses including topics such as cancer cell metabolism, cancer stem cells and cell cycle, apoptosis and cancer, biobanks in cancer research.
Pre-examiner of doctoral dissertations (PhD)
Dr Ivailo Simoff, PhD, SU, 2009; Dr Jitendra Badhai, PhD, UU, 2009; Dr Chiou-Nan Shiue, PhD, KI, 2010; Dr Ann Sofie Fröjmark, PhD, UU, 2010; Dr Jelena Polajeva, PhD, UU 2012; Dr Deniz Özata, PhD, KI, 2015; Anahita Hamadi, PhD, UU, 2015; Vasil Savov, PhD, UU 2016; Chang Liu, PhD, KI; 2016; Xianli Shen, KI, 2017; Fredrik Lackmann, SU, 2017; H.A. M. Sakil, KI, 2017; Patrick Sculicia, PhD, KI 2020; Chiara Pederiva, KI, 2021.
Half time review board for PhD students
Erik Berglund KI, 2013; Lei Zhang, UU, 2012 Yuan Xie, UU 2013; Vasil Savov, UU 2014; Emarndeena Cheteh Haji, KI, 2014; Xianli Shen, KI 2014; Amir Mahani, KI, 2014; Anna Sjösten, UU 2015; Mohammed Mustaq, KI, 2014; Honglei Zhao, KI, 2016; Dalel Saidi, KI, 2016; Satendra Kumar, KI, 2016; Chiara Pederiva, KI, 2017; Patrick Sculicia, KI. 2017; Nadilly Bonagas KI 2019, Jemina Lehto KI 2019, Bishoy Hanna KI 2020.
Supervisor or examinor of many Master of Science or Bachelor of Science thesis.
Chairman of doctoral dissertation
Cecilia Nordfors, PhD, KI, 2015; Michael Mints PhD, KI, 2015; Elin Sjöberg PhD, KI, 2015; Min Guo PhD KI 2020; Bishoy Hanna KI 2021; Rui Shao KI 2022.
Faculty Opponent – doctoral dissertation (PhD)
Amir Nematollani Mahani, KI, Dept LabMed, 2018-06-20.
Education
MSc, Biomedicine, 1999, Karolinska Institutet, Stockholm, Sweden
PhD, Oncology-Experimental Oncology, 2004, Karolinska Institutet, Stockholm, Sweden
Docent, Experimental Pathology, 2012, Karolinska Institutet, Stockholm, Sweden
Academic honours, awards and prizes
Swedish Research Council (VR), Young Researcher award, 2012-2014
Postdoctoral fellowship awarded by the Swedish Cancer Society (Cancerfonden), 2007 - 2010.
Postdoctoral fellowship awarded by the Swedish Research Council (VR), 2005-2006.
SSMF gratefully declined
Grants from among others: Swedish Research Council, Radiumhemmets funds, Magnus Bergvall foundation, Åke Wiberg foundation, over the years 2008-2019.