Affiliated to research
I received a BSc in Biology from Uppsala University in 1982 and PhD in Tumor Biology at Dept. of Pathology, Uppsala University 1989. Title of thesis: “On the role of proto-oncogenes in the differentiation of human hematopoietic tumor cells in vitro". After that, I was a post-doctoral fellow at the Institute for Molecular Biology, Hannover Medical School, Germany, in the lab of Dr. Bernhard Lüscher, 1991-1994. I returned to Sweden and was awarded a position from the Swedish Cancer Foundation (Cancerfonden) as Assistant Professor 1994 at Uppsala University, and then Senior Lecturer and Associate Professor at the Genetic Center, Swedish University for Agricultural Sciences, Uppsala, where I became Professor of Molecular Genetics 2001. In 2007 I was recruited to Karolinska Institutet, Dept of Microbiology, Tumor and Cell Biology as Senior Researcher, where I became professor of Tumor Biology 2011.
Our research focuses on the function, regulation and targeting of the MYC oncoprotein. The MYC oncogene family encodes transcription factors that regulate a vast number of genes involved in cell growth, apoptosis, metabolism, differentiation, senescence, stemness and other cellular functions. Deregulated expression of MYC contributes to the development of over half of all human cancers, and often correlates with advanced stages of disease, resistance to therapy and poor prognosis. Our research addresses questions on how MYC cooperates and interacts with other factors to regulate gene transcription and how this affects biological processes of relevance for tumor development. We are also interested in how MYC’s function, activity and stability is regulated through interaction with such factors. Finally, we are utilizing these insights into strategies to target MYC directly or indirectly in tumor cells. For these purposes we are utilizes a toolbox of different methodologies and tumor systems based on cell culture and mouse models.
My research group is presented here.
Methods to Study Myc-Regulated Cellular Senescence: An Update. Zhang F, Bazzar W, Alzrigat M, Larsson LG Methods Mol Biol 2021 ;2318():241-254
The novel low molecular weight MYC antagonist MYCMI-6 inhibits proliferation and induces apoptosis in breast cancer cells. AlSultan D, Kavanagh E, O'Grady S, Eustace AJ, Castell A, Larsson LG, Crown J, Madden SF, Duffy MJ Invest New Drugs 2021 04;39(2):587-594
Pharmacological inactivation of CDK2 inhibits MYC/BCL-XL-driven leukemia in vivo through induction of cellular senescence. Bazzar W, Bocci M, Hejll E, Högqvist Tabor V, Hydbring P, Grandien A, Alzrigat M, Larsson LG Cell Cycle 2021 01;20(1):23-38
PTEN and DNA-PK determine sensitivity and recovery in response to WEE1 inhibition in human breast cancer. Brunner A, Suryo Rahmanto A, Johansson H, Franco M, Viiliäinen J, Gazi M, Frings O, Fredlund E, Spruck C, Lehtiö J, Rantala JK, Larsson LG, Sangfelt O Elife 2020 07;9():
A selective high affinity MYC-binding compound inhibits MYC:MAX interaction and MYC-dependent tumor cell proliferation. Castell A, Yan Q, Fawkner K, Hydbring P, Zhang F, Verschut V, Franco M, Zakaria SM, Bazzar W, Goodwin J, Zinzalla G, Larsson LG Sci Rep 2018 07;8(1):10064
MYC Modulation around the CDK2/p27/SKP2 Axis. Hydbring P, Castell A, Larsson LG Genes (Basel) 2017 Jun;8(7):
Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation. Bahram F, Hydbring P, Tronnersjö S, Zakaria SM, Frings O, Fahlén S, Nilsson H, Goodwin J, von der Lehr N, Su Y, Lüscher B, Castell A, Larsson LG Oncotarget 2016 Jan;7(3):2837-54
Targeting MYC Translation in Colorectal Cancer. Castell A, Larsson LG Cancer Discov 2015 Jul;5(7):701-3
MYC synergizes with activated BRAFV600E in mouse lung tumor development by suppressing senescence. Tabor V, Bocci M, Alikhani N, Kuiper R, Larsson LG Cancer Res 2014 Aug;74(16):4222-9
CDK-mediated activation of the SCF(FBXO) (28) ubiquitin ligase promotes MYC-driven transcription and tumourigenesis and predicts poor survival in breast cancer. Cepeda D, Ng HF, Sharifi HR, Mahmoudi S, Cerrato VS, Fredlund E, Magnusson K, Nilsson H, Malyukova A, Rantala J, Klevebring D, Viñals F, Bhaskaran N, Zakaria SM, Rahmanto AS, Grotegut S, Nielsen ML, Szigyarto CA, Sun D, Lerner M, Navani S, Widschwendter M, Uhlén M, Jirström K, Pontén F, Wohlschlegel J, Grandér D, Spruck C, Larsson LG, Sangfelt O EMBO Mol Med 2013 Jul;5(7):1067-86
The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Lüscher B, Larsson LG, Hermeking H Proc Natl Acad Sci U S A 2012 Jan;109(4):E187-96
Oncogene- and tumor suppressor gene-mediated suppression of cellular senescence. Larsson LG Semin Cancer Biol 2011 Dec;21(6):367-76
Cdk2 suppresses cellular senescence induced by the c-myc oncogene. Campaner S, Doni M, Hydbring P, Verrecchia A, Bianchi L, Sardella D, Schleker T, Perna D, Tronnersjö S, Murga M, Fernandez-Capetillo O, Barbacid M, Larsson LG, Amati B Nat Cell Biol 2010 Jan;12(1):54-9; sup pp 1-14
Phosphorylation by Cdk2 is required for Myc to repress Ras-induced senescence in cotransformation. Hydbring P, Bahram F, Su Y, Tronnersjö S, Högstrand K, von der Lehr N, Sharifi HR, Lilischkis R, Hein N, Wu S, Vervoorts J, Henriksson M, Grandien A, Lüscher B, Larsson LG Proc Natl Acad Sci U S A 2010 Jan;107(1):58-63
Direct observation of individual endogenous protein complexes in situ by proximity ligation. Söderberg O, Gullberg M, Jarvius M, Ridderstråle K, Leuchowius KJ, Jarvius J, Wester K, Hydbring P, Bahram F, Larsson LG, Landegren U Nat Methods 2006 Dec;3(12):995-1000
c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription. Arabi A, Wu S, Ridderstråle K, Bierhoff H, Shiue C, Fatyol K, Fahlén S, Hydbring P, Söderberg O, Grummt I, Larsson LG, Wright AP Nat Cell Biol 2005 Mar;7(3):303-10
The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C, Hydbring P, Weidung I, Nakayama K, Nakayama KI, Söderberg O, Kerppola TK, Larsson LG Mol Cell 2003 May;11(5):1189-200