Group Pierre Åman

Research summary

Chromosome rearrangements that lead to formation of fusion oncogenes have been identified in many types of leukemia and solid tumors. The FET-group of fusion oncogenes encode chimeric transcription factor proteins containing N-terminal parts of FET proteins juxtaposed to C-terminal DNA binding transcription factor parts.

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We have recently found that all FET-oncoproteins bind and change the activities of the SWI/SNF chromatin remodeling complex. Deregulation of SWI/SNF activity thus provides a unifying pathogenic mechanism for the large group of tumors caused by FET fusion oncoproteins.

Our research focus on the FET-SWI/SNF interactions and its consequences on molecular and cellular levels. Drug tests are also performed in vitro and in vivo and based on findings from our experimental systems.

Research tools and resources

Experimental systems: tumor cell lines, and xenograft models.

Methods: protein–protein interaction studies using recombinant proteins and immunoprecitpitation/mass spectometry. Chromatin immunoprecipitation (ChIP-seq), advanced microscopy, and single cell expression analysis.

Experimental findings are confirmed with studies on human tumor tissues.

Current group members

Pierre Åman, PhD, Professor
Mikael Kubista, Researcher
Christoffer Vannas, PhD student
Heba Albatrok, MSc, Associate Researcher

Selected publications

1. FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex.
   Lindén M, Thomsen C, Grundevik P, Jonasson E, Andersson D, Runnberg R, Dolatabadi S, Vannas C, Luna Santamarίa M, Fagman H, Ståhlberg A, Åman P. EMBO Rep. (2019) Apr 8. pii: e45766. doi: 10.15252/embr.201845766.
    
2. Phosphatidylinositol-3-kinase (PI3K)/Akt Signaling is Functionally Essential in Myxoid Liposarcoma.
   Trautmann M, Cyra M, Isfort I, Jeiler B, Kruger A, Grunewald I, Steinestel K, Altvater B, Rossig C, Hafner S, et al. (2019) Molecular cancer therapeutics, 10.1158/1535-7163.MCT-18-0763
    
3. JAK-STAT signalling controls cancer stem cell properties including chemotherapy resistance in myxoid liposarcoma.
   Dolatabadi S, Jonasson E, Linden M, Fereydouni B, Backsten K, Nilsson M, Martner A, Forootan A, Fagman H, Landberg G, et al. (2019) Int J Cancer, 10.1002/ijc.32123
    
4. Identification of inhibitors regulating cell proliferation and FUS-DDIT3 expression in myxoid liposarcoma using combined DNA, mRNA, and protein analyses.
   Svec D, Dolatabadi S, Thomsen C, Cordes N, Shannon M, Fitzpatrick P, Landberg G, Aman P, Stahlberg A (2018) Lab Invest 98: 957-967
    
5. FUS-DDIT3 Fusion Protein-Driven IGF-IR Signaling is a Therapeutic Target in Myxoid Liposarcoma.
   Trautmann M, Menzel J, Bertling C, Cyra M, Isfort I, Steinestel K, Elges S, Grunewald I, Altvater B, Rossig C, et al. (2017) Clin Cancer Res 23: 6227-6238
    
6. A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma.
   Tomic TT, Olausson J, Wilzen A, Sabel M, Truve K, Sjogren H, Dosa S, Tisell M, Lannering B, Enlund F, et al. (2017) PLoS One 12: e0175638
    
7. Cell Cycle and Cell Size Dependent Gene Expression Reveals Distinct Subpopulations at Single-Cell Level.
   Dolatabadi S, Candia J, Akrap N, Vannas C, Tesan Tomic T, Losert W, Landberg G, Aman P, Stahlberg A (2017) Front Genet 8:1
    
8. HSP90 inhibition blocks ERBB3 and RET phosphorylation in myxoid/round cell liposarcoma and causes massive cell death in vitro and in vivo.
   Safavi S, Jarnum S, Vannas C, Udhane S, Jonasson E, Tomic TT, Grundevik P, Fagman H, Hansson M, Kalender Z, et al. (2016) Oncotarget 7: 433-445
    
9. Establishment and characterization of a new human myxoid liposarcoma cell line (DL-221) with the FUS-DDIT3 translocation.
   de Graaff MA, Yu JS, Beird HC, Ingram DR, Nguyen T, Juehui Liu J, Bolshakov S, Szuhai K, Aman P, Torres KE, et al. (2016) Lab Invest 96: 885-894
    
10. HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat.
    Angelika Ihle M, Merkelbach-Bruse S, Hartmann W, Bauer S, Ratner N, Sonobe H, Nishio J, Larsson O, Aman P, Pedeutour F, et al. (2016) J Pathol Clin Res 2: 59-71

More group Pierre Åman publications on PubMed