Breadcrumb

Research summary

Our overall goal is to increase the survival and improve the quality of life for patients suffering from sarcomas characterized by FET (FUS, EWSR1, TAF15) fusion oncogenes (FET sarcomas), including more than 20 pediatric and adult cancer entities.

To accomplish this we are identifying and targeting FET fusion oncogene-specific features by applying genomics, transcriptomics and proteomics approaches that are associated with tumor development and therapy resistance. We have a particular interest in chromatin remodeling and signaling pathways like JAK-STAT and their molecular interactions with FET fusion oncoproteins. The cell transformation mechanism of FET fusion oncogenes are studied using innovative 3D and in vivo experimental models.

Another challenge in management of cancer patients is to monitor treatment efficiency and detect potential relapse at an early stage. Analysis of circulating cell-free tumor DNA (ctDNA) in non-invasive liquid biopsies allows us to address this issue. However, standard analytical techniques cannot be applied, since ctDNA is both heavily fragmented and only available in low concentrations.

To overcome these obstacles associated we have established a complete clinical workflow, from sampling to data interpretation, using innovative and ultrasensitive detection technologies. Our analytical platform is applied to sarcomas as well as several other cancer forms in collaboration.

Our specific aims include:

  • To define tumor cell hierarchy and to identify key cell fate decisions for drug target identification in FET sarcomas using functional single-cell analysis.
  • To define the mechanisms of FET fusion oncogenes.
  • To develop tumor bioreactors for next generation diagnostics and drug test systems, using 3D bioprinting and patient-derived scaffolds.
  • To determine the role of microenvironment in relation to specific cell types using 3D model systems.
  • To develop non-invasive molecular methods in cancer diagnostics and prognostics, including DNA-, RNA-, protein- and cell clonality analyses.
  • To clinically evaluate and implement the use of ctDNA.

Research tools and resources

We apply a wide range of methods within the area of cell- and molecular biology. These include 3D culture systems using both patient-derived and bioprinted scaffolds with stem cells, tumor cell lines, reporter cell lines, primary cells and mouse xenografts. Molecular techniques include several NGS approaches, qPCR, digital PCR, MS, IP, PLA and FACS.

We have a special interest in single-cell and single-molecule techniques that we develop in house and apply to better understand biological processes. We also perform bioinformatics, focusing on DNA and RNA analyses. Clinical samples include various types of tissue biopsies and liquid biopsies, such as blood and urine. We work closely with the Translational Genomics Platform at Wallenberg Centre for Molecular and Translational Medicine.

Current group members

Anders Ståhlberg, PhD, Professor, PI
Tobias Österlund, PhD, Bioinformatician/Staff scientist
Emma Jonasson, PhD, Staff scientist
Parmida Ranji, PhD, Staff scientist
Daniel Andersson, PhD, Staff scientist
Anna Gustafsson, PhD, Postdoc
Peter Micallef, PhD, Postdoc
Malin Lindén, PhD, Postdoc
Firaol Tamiru, PhD, Postdoc
Amin Forootan, MSc, PhD student (with MultiD Analyses)
Lisa Andersson, MSc, PhD student
Manuel Luna Santa-María, MSc, PhD Student
Florian Puls, MD, PhD student
Mandy Escobar, MSc, PhD Student
Vilma Canfjorden, MSc, PhD student
Heba Albatrok, MSc, Associate Researcher
Pia Mouhanna, MSc, Associate Researcher
Christoffer Vannas, MD, Associated PhD student
Eivind Stensrud, MSc, Associated PhD student (with eDNA Solutions)
Hana Komic, MSc, Associated PhD student
Elisabeth Mellström, MD, Associated PhD student
Marta Berndsen, MD, Associated PhD student
Ida Rahmqvist, MSc, Associated PhD student
Jacob Malchau Lauesgaard, MD, Associated PhD student
Anna Fager, MD, Associated PhD student

We have openings for MSc thesis projects.

Selected recent publications

  1. UMIErrorCorrect and UMIAnalyzer: Software for Consensus Read Generation, Error Correction, and Visualization Using Unique Molecular Identifiers.
    Österlund T, Filges S, Johansson G, Ståhlberg A. Clin Chem. 2022 Nov 3;68(11):1425-1435.
     

  2. FUS-DDIT3 Fusion Oncoprotein Expression Affects JAK-STAT Signaling in Myxoid Liposarcoma.
    Dolatabadi S, Jonasson E, Andersson L, Luna Santa Maria M, Österlund T, Åman P, Ståhlberg A. Frontiers in Oncology, 2022, 12:816894.
     

  3. FET fusion oncoproteins with BRD4 and SWI/SNF chromatin remodeling complex subtypes.
    Lindén M, VannasC, ÖsterlundT, AnderssonL, OsmanA, EscobarM, FagmanH, StåhlbergA, Åman P. Molecular Oncology, 2022, doi: 10.1002/1878-0261.13195

     
  4. Monitoring circulating tumor-DNA during surgical treatment in patients with gastrointestinal stromal tumors.  
    JohanssonG, BerndsenM, LindskogS, ÖsterlundT, FagmanH, MuthA, StåhlbergA. Molecular Cancer Therapeutics, 2021, 20:2568-76.         

     
  5. Digital quantification of chemical oligonucleotide synthesis errors.  
    Filges S, Mouhanna P, Ståhlberg A. Clinical Chemistry, 2021, 67:1384-94

     
  6. The PEMDAC phase 2 study pembrolizumab and entinostat in patients with metastatic uveal melanoma.
    Ny L, Jespersen H, Karlsson J, Alsén S, Filges S, All-Eriksson, Andersson B, Carneiro A, Helgadottir H, Levin M, Ljuslinder I, Olofsson Bagge R, Sah V, Stierner U, Ståhlberg A, Ullenhag G, Nilsson LM, Nilsson JA. Nature Communications, 2021, 12:5155.
     
  7. Ultrasensitive DNA immune repertoire sequencing using unique molecular identifiers.
    JohanssonG, Kaltak M, RîmniceanuC, SinghAK, LyckeJ, MalmeströmC, HühnM, VaaralaO, CardellS, Ståhlberg A. Clinical Chemistry, 2020, 66:1228-37.

     
  8. Total mRNA quantification in single cells: sarcoma cell heterogeneity.
    Jonasson E, Andersson L, Dolatabadi S, Ghannoum S, Åman P, Ståhlberg A. Cells, 2020, 9:759.

     
  9. Patient-derived scaffolds uncover breast cancer promoting properties of the microenvironment.
    Landberg G, Fitzpatrick P, Isakson P, Jonasson E, Karlsson J, Larsson E, Svanström A, Rafnsdottir S, Persson E, Gustafsson A, Andersson D, Rosendahl J, Petronis S, Ranji P, Gregersson P, Magnusson Y, Håkansson J, Ståhlberg A.
    Biomaterials, 2020, 235:119705.
     
  10. Circulating cell-free tumor DNA analysis in pediatric cancers.
    Andersson D, Fagman H, Dalin MG, Ståhlberg A. Moleular Aspects of Medicine, 2020, 72:100819.

More group Anders Ståhlberg publications on PubMed

 

Anders Ståhlberg
Photo: Emelie Asplund

Contact information

Anders Ståhlberg

E-mail: Anders Ståhlberg

Visiting address:
Sahlgrenska Center
for Cancer Research,
Medicinaregatan 1F
413 90 Gothenburg
 

Navigate to video: Blood-based diagnostics of sarcomas
Video (5:54)
Blood-based diagnostics of sarcomas

Research presentation

Summary of ongoing research about blood-based biomarkers in patients diagnosed with sarcomas.

Navigate to video: FET oncogene sarcoma biology and drug development
Video (5:44)
FET oncogene sarcoma biology and drug development

Research presentation

Summary of ongoing research about novel interventions for patients diagnosed with FET sarcomas.

In collaboration with Professor Pierre Åman.

Translational Genomics Platform

Photo: Johan Wingborg

Ultrasensitive Nucleic Acids Analysis

This platform is a research initiative to bring innovations within nucleic acid analysis into healthcare. Ultrasensitive sequencing techniques can accurately detect individual disease-associated molecules in liquid biopsies sampled from different body fluids. In cancer, analysis of tumor-derived molecules in blood provides detailed diagnostic and prognostic information. This precision medicine approach opens up the possibility for early diagnostics, monitoring of treatment efficacy and detection of relapses.

The Translational Genomics Platform is a partner in several ongoing national and international studies, especially at Sahlgrenska University Hospital, exploring the clinical utility of ultrasensitive nucleic acid analysis.

Our specific aims include:

  • To develop ultrasensitive molecular techniques that enable the analysis of individual nucleic acid molecules with nucleotide resolution and their modifications.
  • To demonstrate the clinical utility of analyzing circulating tumor-derived nucleic acids in liquid biopsies.
  • To develop and validate liquid biopsy workflows, from sampling to data analysis.
  • To facilitate and support clinical studies at all stages using liquid biopsy analysis.

Current technologies lack sensitivity to reliably detect rare variant alleles or are limited to interrogate few pre-defined variants. To overcome these challenges we developed “Simple, multiplexed, PCR-based barcoding of DNA for sensitive allele variant detection using sequencing” (SiMSen-Seq).

This technique has a straightforward workflow that allows flexible targeting of multiple sequences and may be applied on minute quantities of DNA (< 5 ng DNA). SiMSen-Seq enables the detection and quantification of individual DNA molecules with single nucleotide resolution, covering several kilobases of DNA. It can be applied to essential all clinical sample types, including body fluids such as blood, urine, saliva, cerebrospinal fluid and pleural fluid. Data analysis is standardized and can be performed with freely available open source softwares.

The Translational Genomics Platform uses SiMSen-Seq and related technologies to meet the clinical need to diagnose and monitor patients with high sensitivity and specificity. Detection of extremely rare variant alleles within a complex mixture of DNA molecules is also becoming increasingly relevant in many other areas, such as prenatal testing, forensics, immunology, pathogen detection, neurological and metabolic diseases. These applications are developed in collaborations with experts in respective fields.