We are a research group at the Department of Immunology, Genetics and Pathology (IGP) at Uppsala University. Our primary research goals are directed towards understanding the complex regulation in cancer cells, ultimately aiming at new therapeutic strategies. Combining mathematical and experimental methods, our lab focuses on cancers of the nervous system. This is a challenging but important area of investigation, where IGP has an excellent unit with complementary expertise. On this page, you will find information about our cross-disciplinary team and projects. You are welcome to contact us for further information.

Our Research
In the news
Swedish Cancer Society 2017 Senior Investigator Award. 3.2 million Euro grant awarded for our research by the Swedish Strategic Research Foundation. Venerable brain cancer cell line faces identity crisis
Sven
Nelander
Associate professor, Group Leader
Cecilia
Krona
Senior Researcher
Evgenia
Gubanova
Post Doc
Soumi
Kundu
Post Doc
Karl
Holmberg
Olausson
Post Doc
Ludmilla
Elfineh
Research Engineer
Caroline
Wärn
Research Engineer
Sathishkumar
Baskaran
PhD Student
Patrik
Johansson
PhD Student
Elin
Almstedt
PhD Student
Emil
Rosén
PhD Student
Neda
Hekmati
MSc Student

High resolution molecular mapping and functional biology of brain tumor stem cell lines

In this project, we develop systems biology strategies for the targeting of cancer stem cells (CSCs) in individual patients suffering from glioblastoma. CSCs are crucial for the maintenance and progression of these cancers, but the systems-scale characterization of CSCs has so far been limited by the lack of relevant model systems for large-scale functional studies. Our project takes advantage of the Human Glioma Cell Culture—HGCC biobank, a world-unique clinical material that comprises an extensive collection of early-passage glioblastoma CSC cultures derived from more than a hundred consecutive patient cases at Uppsala University Hospital during 2010-2012.


Image: Tobias Bergström (hgcc.se)

Cancer Landscapes:
an interactive, global map of regulation in human cancer

A major challenge in current cancer research is to gain biological insight from large scale molecular data from patient samples. In this project, we invent new mathematical methods to construct regulatory maps of multiple cancer diagnoses. Our system uses data from both public sources and from IGP/SciLifeLab. The results are made available on a new web resource, Cancer Landscapes. A unique feature of Cancer Landscapes is that very complex data become available in an intuitive form, which lab biologists can use to design experiments.


New mathematical models of brain tumor progression and invasiveness

Brain tumors are characterized by invasive growth, which makes surgical resection inefficient. In this project, we develop new mathematical simulations of brain tumor growth to understand the principles of brain tumor invasiveness, and to determine new strategies to inhibit invasive growth. The models should be applicable to designing relevant cell screens for glioblastoma and cytometry-based patient prognostics.


Publication spotlight

Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.

Jiyang Y et al
Cell Reports 2017

Membrane-depolarizing channel blockers induce selective glioma cell death by impairing nutrient transport and unfolded protein/amino acid responses.

Niklasson M et al
Cancer Research 2017

c-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas.

Heiland DM et al
Oncotarget 2017

Case Specific Potentiation of Glioblastoma Drugs by Pterostilbene

Linnéa Schmidt et al
Oncotarget 2016

Integrative modeling reveals Annexin A2-dependent control of mesenchymal glioblastoma

Teresia Kling et al
EBioMedicine 2016

Origin of the U87MG glioma cell line: Good news and bad news

Allen M. et al.
Science Translational Medicine 2016

High sensitivity isoelectric focusing to establish a signaling biomarker for the diagnosis of human colorectal cancer.

Padhan N, et al.
BMC Cancer 2016

ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells.

Wee B., et al.
Sci Rep 2016

Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.

Mitchell JS, Li N, et al.
Nat Commun, 2016

Travelling wave analysis of a mathematical model of glioblastoma growth.

Philip Gerlee, Sven Nelander
Mathematical Biosciences, 2016

Simultaneous Multiplexed Measurement of RNA and Proteins in Single Cells.

Darmanis et al.
Cell Reports, 2016

The human glioblastoma cell culture resource: validated cell models representing all molecular subtypes.

Yuan Xie* Tobias Bergström*, Yiwen Jiang*, Patrik Johansson*, Voichita Dana Marinescu, Nanna Lindberg, Anna Segerman, Grzegorz Wicher, Mia Niklasson, Sathishkumar Baskaran, Smitha Sreedharan, Isabelle Everlien, Marianne Kastemar, Annika Hermansson, Lioudmila Elfineh, Sylwia Libard, Eric Charles Holland, Göran Hesselager, Irina Alafuzoff, Bengt Westermark*, Sven Nelander*, Karin Forsberg-Nilsson*, Lene Uhrbom*
EBioMedicine 2015

Efficient exploration of pan-cancer networks by generalized covariance selection and interactive web content.

Kling, T*, Johansson, P*, Sanchez J, Marinescu V, Jörnsten R, Nelander S
Nucleic Acids research 2015

High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes.

Dijksterhuis et al.
Exp Cell Res, 2015

Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells.

Roy et al.
Oncotarget 2015

Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

Swaminathan et al.
Nature Communications 2015

Vulnerability of glioblastoma cells to catastrophic vacuolization and death induced by a small molecule.

Kitambi SS, Toledo EM, Usoskin D, Wee S, Harisankar A, Svensson R, Sigmundsson K, Kalderén C, Niklasson M, Kundu S, Aranda S, Westermark B, Uhrbom L, Andäng M, Damberg P, Nelander S, Arenas E, Artursson P, Walfridsson J, Forsberg Nilsson K, Hammarström LG, Ernfors P.
Cell. 2014 Apr 10;157(2):313-28. doi: 10.1016/j.cell.2014.02.021. Epub 2014 Mar 20.

Selective calcium sensitivity in immature glioma cancer stem cells.

Wee S, Niklasson M, Marinescu VD, Segerman A, Schmidt L, Hermansson A, Dirks P, Forsberg-Nilsson K, Westermark B, Uhrbom L, Linnarsson S, Nelander S, Andäng M.
PLoS One. 2014 Dec 22;9(12):e115698. doi: 10.1371/journal.pone.0115698. eCollection 2014.

Comparative drug pair screening across multiple glioblastoma cell lines reveals novel drug-drug interactions.

Schmidt L, Kling T, Monsefi N, Olsson M, Hansson C, Baskaran S, Lundgren B, Martens U, Häggblad M, Westermark B, Forsberg Nilsson K, Uhrbom L, Karlsson-Lindahl L, Gerlee P, Nelander S
Neuro Oncol. 2013 Nov;15(11):1469-78. doi: 10.1093/neuonc/not111. Epub 2013 Oct 6.

The Cancer Genome Atlas Pan-Cancer analysis project.

Cancer Genome Atlas Research Network, Weinstein JN, Collisson EA, Mills GB, Shaw KR, Ozenberger BA, Ellrott K, Shmulevich I, Sander C, Stuart JM
Nat Genet. 2013 Oct;45(10):1113-20. doi: 10.1038/ng.2764.

Searching for synergies: matrix algebraic approaches for efficient pair screening

Philip Gerlee, Linnéa Schmidt, Naser Monsefi, Teresia Kling, Rebecka Jörnsten, Sven Nelander
PLoS One. 2013 Jul 25;8(7):e68598. doi: 10.1371/journal.pone.0068598. Print 2013.

The impact of phenotypic switching on glioma growth and progression

Philip Gerlee and Sven Nelander
PLoS Comput Biol. 2012;8(6):e1002556. doi: 10.1371/journal.pcbi.1002556. Epub 2012 Jun 14.

Clinically Significant Copy Number Alterations and Complex Rearrangements of MYB and NFIB in Head and Neck Adenoid Cystic Carcinoma

Marta Persson, Ywonne Andren, Christopher Moskaluk, Henry Frierson, Susanna Cooke, Andrew Futreal, Teresia Kling, Sven Nelander, Anders Nordkvist, Fredrik Persson, and Goran Stenman
Genes Chromosomes Cancer. 2012 Aug;51(8):805-17. doi: 10.1002/gcc.21965. Epub 2012 Apr 16.

System-Scale Network Modeling of Cancer Using EPoC

Abenius T, Jörnsten R, Kling T, Schmidt L, Sánchez J, Nelander S.
Adv Exp Med Biol. 2012;736:617-43.

Network modeling of the transcriptional effects of copy number aberrations in glioblastoma

Rebecka Jörnsten, Tobias Abenius, Teresia Kling, Linnea Schmidt, Erik Johansson, Torbjörn Nordling, Bodil Nordlander, Chris Sander, Peter Gennemark, Keiko Funa, Björn Nilsson, Linda Lindahl, Sven Nelander
Molecular Systems Biology 2011; 7:486

Off-target effects dominate a large-scale RNAi screen for modulators of the TGF-beta pathway and reveal microRNA regulation of TGFBR2

Nikolaus Schultz, Dina R Marenstein, Dino A De Angelis, Wei-Qing Wang, Sven Nelander, Anders Jacobsen, Debora S Marks, Joan Massague and Chris Sander
Silence 2011, 2:3

Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy

Barretina J, Taylor BS, Banerji S, Ramos AH, Lagos-Quintana M, Decarolis PL, Shah K, Socci ND, Weir BA, Ho A, Chiang DY, Reva B, Mermel CH, Getz G, Antipin Y, Beroukhim R, Major JE, Hatton C, Nicoletti R, Hanna M, Sharpe T, Fennell TJ, Cibulskis K, Onofrio RC, Saito T, Shukla N, Lau C, Nelander S, Silver SJ, Sougnez C, Viale A, Winckler W, Maki RG, Garraway LA, Lash A, Greulich H, Root DE, Sellers WR, Schwartz GK, Antonescu CR, Lander ES, Varmus HE, Ladanyi M, Sander C, Meyerson M, Singer S.
Nature Genetics. 2010 Aug;42(8):715-21.

Models from experiments: combinatorial drug perturbations of cancer cells

Nelander S, Wang W, Nilsson B, She QB, Pratilas C, Rosen N, Gennemark P, Sander C.
Molecular Systems Biology 2008;4:216. Epub 2008 Sep 2.

An improved method for detecting and delineating genomic regions with altered gene expression in cancer

Nilsson B, Johansson M, Heyden A, Nelander S, Fioretos T.
Genome Biology 2008 Jan 21;9(1):R13.

Are you interested in opportunities in cancer systems biology?

Do you want to conduct a challenging project in state-of-the-art computational biology? Do not hesitate to contact us.