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Frits Alan Thorsen

Frits Alan Thorsen

Position

Professor, Platform Leader Molecular Imaging Center

Affiliation

E-mail
frits.thorsen@uib.no
Phone number
+47 95749681
+47 55586272
Visitor address
Jonas Lies vei 91
5009 Bergen
Postal address
P.O. Box 7804
NO-5020 Bergen
Norway

Frits Alan Thorsen

Position

Professor, Platform Leader Molecular Imaging Center

Affiliation

Research groups

Research

Background

Brain metastasis is a complication occurring in one third of all cancer patients. Metastases to the brain occur 10 times more often than primary malignant brain tumors. The most common sources of metastatic brain lesions involve the lung (50-60%), breast (15-20%), skin (5-10%) and gastrointestinal tract (4-6%).

Patients with metastatic spread to the central nervous system (CNS) have a poor prognosis. Treatment strategies available today are ineffective, with low response rates, as current chemotherapeutic agents are ineffective. Clearly there is a need for suitable animal models in which spontaneous CNS metastases develop when cancer cells metastasize from the primary lesion in a manner that reflects the patient setting. 

Development of new metastatic animal models

We have recently developed novel model systems where tumor cells from human melanoma brain metastases are injected systemically in immunodeficient mice and metastasize to the mouse brain. This animal model recapitulates most steps of the metastatic cascade, and a better understanding of the molecular mechanisms behind tumor metastasis may thus be obtained.

Ongoing research activities

Our work focuses on 3 main avenues:

We have performed genetic studies on our model systems, and performed bioinformatics analysis to determine a brain metastasis-specific gene signature. This work has resulted in determination of several novel drugs originally used for other conditions than cancer, which shows inhibitory effects on brain metastases in vivo.  

We are also studying the blood-brain barrier (BBB), which prevents therapeutic drugs from entering the brain. We are currently collaborating with partners from Germany, UK, China and the US, to modulate the BBB for prevention and treatment of brain metastases.

Currently, we are studying the effect of exosomes on the tumor microenvironment, and have encouraging data showing that miRNAs delivered to the brain by exosomes are important in preparing the pre-metastatic niche. This is an ongoing collaboration with our partners at Shandong University, China, and University of Luxembourg.

Outreach

POPULAR SCIENCE ARTICLES 

1.   Mottok kinesiske forskningsmidler. Medical Faculty web site, University of Bergen, October 2, 2020 (In Norwegian). https://www.uib.no/med/139047/mottok-kinesiske-forskningsmidler

2.   Fikk kinesisk æresprofessorat. På Høyden, October 31, 2018 (In Norwegian). http://pahoyden.no/2018/10/fikk-kinesisk-aeresprofessorat

3.   Slik jobber 100 forskere i Bergen hver dag for å løse kreftgåten. Bergens Tidende, July 22, 2017 (In Norwegian). https://www.bt.no/btmagasinet/i/voqmV/Bruker-designermus-for-a-lose-kreftgaten?utm_campaign=Echobox&utm_medium=Social&utm_source=Facebook#link_time=1500704688

4.   30 millioner til kreftforskning. University of Bergen web site, Nov 1, 2016 (In Norwegian). http://www.uib.no/mofa/102056/30-millioner-til-kreftforskning

5.   207 millioner til kreftforskning. Kreftforeningen (blog), Oct 27, 2015 (In Norwegian). (http://www.kreftforeningens-blogg.no/2015/10/207-millioner-til-kreftforskning/ )

6.     Nøttestoff reduserte kreft i musehjerner. Forskning.no, July 25, 2015 (In Norwegian). https://forskning.no/2015/07/nottestoff-reduserte-kreft-i-musehjerner

7.   Forsker: Jeg trodde det var for godt til å være sant. Bergens Tidende, July 2, 2015 (In Norwegian). (http://www.bt.no/nyheter/lokalt/--Jeg-har-ikke-sett-lignende-i-mine-20-ar-som-forsker-3393563.html ).

8.   Nøtter kan redusere kreft med spredning til hjernen. Kreftforeningen.no, July 1, 2015 (In Norwegian). (https://kreftforeningen.no/forskning/forskningsprosjekter-vi-stotter/notter-kan-redusere-kreft-med-spredning-til-hjernen/?utm_source=apsis-anp-3&utm_medium=email&utm_content=unspecified&utm_campaign=01.%20juli ).

9.   Nøtter kan redusere kreft med spredning til hjernen. University of Bergen web site, July 1, 2015 (In Norwegian). (http://www.uib.no/aktuelt/89958/n%C3%B8tter-kan-redusere-kreft-med-spredning-til-hjernen ).

10.   Frits Thorsen in Bergens Tidende: Exciting findings in preventing metastatic spreading. http://www.uib.no/en/rg/mic/90150/frits-thorsen-bergens-tidende-exciting-findings-preventing-metastatic-spreading   

Teaching

1989-2002 Teacher in Radiation Physics, Haukeland University Hospital, Bergen, Norway.

1991-1994 Teacher, Faculty of Health and Social Sciences, Bergen Univ. College, Norway.

1993-2006 Clinical Consultant, Elekta Instrument AB, Stockholm, Sweden

2004-2023 Histology and Anatomy Teacher, Dept. of Biomedicine, UiB.

2008-2022 Invited Lecturer at 18 International Cancer Conferences.

 

Publications
Academic article
Masters thesis
Editorial
Article in business/trade/industry journal
Academic literature review
Poster
Doctoral dissertation
Academic lecture
Lecture
Medical Student Research Thesis
Abstract

See a complete overview of publications in Cristin.

Publication list 2013-2023

* = shared last authorship

  1. Rigg E, Wang J, Xue Z, Lunavat T, Liu G, Hoang T, Parajuli H, Han M, Bjerkvig R, Nazarov P, Nicot N, Kreis S, Margue CW, Nomigni MT, Utikal J, Miletic H, Sundstrøm T, Li X, Thorsen F. Inhibition of extracellular vesicle derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes. J Extracell Ves 2023, Oct; 12(10):e12363. doi: 10.1002/jev2.12363.
  2. Spitzer D, Guérit S, Khel M, Pütz T, Zinke J, Jia X, Sommer K, Filipski K, Thorsen F, Freiman T, Harter P, Reiss Y, Liebner S, Di Tacchio M, Devraj K. A flow cytometry based protocol for syngenic isolation of neurovascular unit cells from mouse and human tissues. Nat Protoc 2023 May, 18(5):1510-1542. doi:10.1038/s41596-023-00805-y.
  3. Taule EM, Schipmann-Miletic S, Thorsen F, Johannessen TA, Miletic H, Storstein A, Oltedal L, Sundstrøm T. Hjernemetastasar – diagnostikk og behandling. Tidsskr Nor Laegeforen 2022, Oct 10;142(14). doi: 10.4045/tidsskr.21.0809. Review, in Norwegian.
  4. Reigstad A, Herdlevær CF, Rigg E, Hoang T, Bjørnstad OV, Aasen SN, Preiss J, Haan C, Sundstrøm T, Thorsen F. CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells. PLoS One 2022 Sep 9, 17(9):e0273711. doi: 10.1371/journal.pone.0273711. [IF 3.24]
  5. Sibson NR, Thorsen F, Sarmiente Soto M. The role of the immune response in brain metastasis. Front Oncol 10 May 2022. doi: 10.3389/fonc.2022.922700. Editorial.
  6. Aasen SN, Espedal H, Keunen O, Adamsen TCH, Bjerkvig R*, Thorsen F*. Current landscape and future perspectives in preclinical MR and PET imaging of brain metastasis. Neuro-Oncol Adv, 3(1):1-14, 2021. https://doi.org/10.1093/noajnl/vdab151. Review.
  7. Mannsåker TA, Hoang T, Aasen SN, Bjørnstad OV, Parajuli H, Sundstrøm T, Thorsen F. Cabozantinib is effective in melanoma brain metastasis cell lines and affects key signaling pathways. Int J Mol Sci 2021 Nov 14, 22(22):12296. https://doi.org/10.3390/ijms222212296. [IF 5.923].
  8. Zhang Y, Kong Y, Ma Y, Ni S, Wikerholmen T, Xi K, Zhao F, Zhao Z, Wang J, Huang B, Chen A, Yao Z, Han M, Feng Z, Hu Y, Thorsen F*, Wang J*, Li X*. Loss of COPZ1 induces NCOA4 mediated autophagy and ferroptosis in glioblastoma cell lines. Oncogene 2021 Jan 8, 40(8):1425-1439. doi: 10.1038/s41388-020-01622-3.
  9. Zhang Y, Fu X, Jia J, Wikerholmen T, Xi K, Kong Y, Wang J, Chen H, Ma Y, Li Z, Wang C, Qi Q, Thorsen F, Wang J, Cui J, Li X, Ni S. Glioblastoma therapy using codelivery of cisplatin and gluthathione peroxidase targeting siRNA from iron oxide particles. ACS Appl Mater Interfaces 2020 Sep 4. 
  10. Ji J, Ding K, Luo T, Zhang X, Chen A, Zhang D, Li G, Thorsen F, Huang B, Li X, Wang J. TRIM22 activates NF-κB signaling in glioblastoma by accelerating the degradation of IκBα. Cell Death & Diff 2020 Aug 19, 18:6938-15. 
  11. Kong Y, Feng Z, Zhang Y, Liu X, Yuan M, Zhao Z, Huang B, Chen A, Zhang D, Thorsen F, Wang J, Yang N, Li X. Identification of immune-related genes contributing to the development of glioblastoma using weighted gene co-expression network analysis. Front Immunol 2020 July 16, 11:1281. 
  12. Valiente M, Van Swearingen AED, Anders C, Bairoch A, Boire A, Bos P, Cittelly D, Erez N, Ferraro G, Fukumura D, Gril BM, Herlyn M, Holmen SL, Jain RK, Joyce JA, Lorger M, Massagué J, Neman J, Sibson N, Steeg P, Thorsen F, Young L, Vareslija D, Vultur A, Weis-García F, Winkler F. Brain Metastasis Cell Lines Panel: a public resource of organotropic cell lines. Cancer Res 2020 July 8. 
  13. Feng Z, Zhou W, Wang J, Qi Q, Han M, Kong Y, Zhang Y, Chen A, Huang B, Chen A, Zhang D, Li W, Zhang Q, Bjerkvig R, Wang J*, Thorsen F*, Li X*. Reduced expression of proteolipid 2 increases ER-stress-induced apoptosis and autophagy in glioblastoma. J Cell Mol Med 2020 Mar 17, 24(5):2847-2856.
  14. Zhang X, Ding K, Ji J, Parajuli H, Aasen SN, Espedal H, Huang B, Chen A, Wang J*, Li X*, Thorsen F*. Trifluoperazine prolongs the survival of experimental brain metastases by STAT3-dependent lysosome membrane permeabilization. Am J Cancer Res 2020 Feb 1, 10(2):545-563. 
  15. Han M, Wang S, Fritah S, Zhou W, Yang N, Huang B, Chen A, Li G, Miletic H, Thorsen F, Bjerkvig R, Li X, Wang J. Interfering with long non-coding RNA MIR22HG processing inhibits glioma progression through suppression of Wnt/b-catenin signalling. Brain 2020 Feb 1, 143(2):512-530.  
  16. Ji J, Ding K, LuoT, Xu R, Zhang X, Huang B, Chen A, Zhang D, Miletic H, Bjerkvig R*, Thorsen F*, Wang J*, Li X*. PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1. Oncogene 2020 Jan 11, 39(5):1125-1139. 
  17. Han M, Wang S, Zhao W, Kong Y, Huang B, Chen A, Saed HS, Li G, Miletic H, Thorsen F, Bjerkvig R, Li X, Wang J. Therapeutic implications of altered cholesterol homeostasis mediated by loss of CYP46A1 in human glioblastoma. EMBO Mol Med, 2020 Jan 9;12(1):e10924. 
  18. Bernatz S, Ilina E, Devraj K, Harter PN, Mueller K, Kleber S, Braun Y, Penski C, Renner C, Halder R, Jennewein L, Solbach C, Thorsen F, Pestalozzi BC, Mischo A, Mittelbronn M. Impact of docetaxel on blood-brain barrier function and formation of breast cancer brain metastases. J Exp & Clin Cancer Res 2019 Oct 29;38(1):434. 
  19. Ji J, Xu R, Ding K, Bao G, Zhang X, Huang B, Wang X, Martinez A, Wang X, Li G, Miletic H, Thorsen F, Bjerkvig R, Xiang L, Han B, Chen A, Li X, Wang J. Long noncoding RNA SChLAP1 forms a growth promoting complex with HNRNPL in human glioblastoma through stabilization and activation of NF-kB signalling. Clin Cancer Res 2019 Sep. 6.
  20. Aasen SN, Espedal H, Holte CF, Keunen O, Karlsen TV, Tenstad O, Maherally Z, Miletic H, Hoang T, Eikeland AV, Baghirov H, Olberg DE, Pilkington GJ, Sarkar G, Jenkins R, Sundstrøm T, Bjerkvig R, Thorsen F. Improved drug delivery to experimental melanoma brain metastasis by peptide-mediated permeabilization of the blood-brain barrier. Mol Cancer Ther 2019 Aug 29. 
  21. Aasen SN, Parajuli H, Roy K, Hoang T, Stokke K, Wang J, Feng Z, Bjerkvig R, Thorsen F. Effective treatment of metastatic melanoma by combining MAPK and PI3K signaling pathway inhibitors. Int J Mol Sci 20(17):4235, Aug 29, 2019. 
  22. Sundstrøm T, Prestegarden L, Azuaje F, Røsland GV, Varughese JK, Aasen SN, Bernatz S, Braun Y, Harter PN, Skaftnesmo KO, Inghem ES, Mahakian LM, Tam S, Tepper CG, Petersen K, Ferrara KW, Tronstad KJ, Lund-Johansen M, Bjerkvig R*, Thorsen F*. Inhibition of mitochondrial respiration prevents BRAF-mutant melanoma brain metastasis. Acta Neuropathol Comm 7:55, Apr 10, 2019. doi: 10.1186/s40478-019-0712-8.
  23. Bjerkvig R, Thorsen F. Glioblastoma: a prognostic value of AMT-PET? Neuro-Oncol 21(2):146-147, Feb 14, 2019. 
  24. Wang J, Qi Q, Zhou W, Feng Z, Huang B, Chen A, Zhang D, Li W, Zhang Q, Bjerkvig R, Prestegarden L, Thorsen F, Li X, Wang J. Inhibition of glioma growth by flavokawain B is mediated through endoplasmatic reticulum stress induced autophagy. Autophagy 2018 Jul 19.
  25. Zeiner PS, Zinke J, Kowalewski DJ, Bernatz S, Tichy J, Ronellenfitsch MW, Thorsen F, Berger A, Forster MT, Muller A, Steinbach JP, Beschorner R, Wischhusen J, Kvasnicka HM, Plate KH, Stefanovic S, Weide B, Mittelbronn M, Harter PN. CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival. Acta Neuropathol Comm 6:18, 2018. 
  26. Baghirov H, Snipstad S, Sulheim E, Berg S, Hansen R, Thorsen F, Mørch Y, de Lange Davies C, Åslund ÅKO. Ultrasound-mediated delivery and distribution of polymeric nanoparticles in the normal brain parenchyma of a metastatic brain tumour model. PLoS ONE, 13(1):e0191102, 2018. 
  27. Zhang X, Xu R, Zhang C, Xu Y, Han M, Huang B, Chen A, Qiu C, Thorsen F, Prestegarden L, Bjerkvig R, Wang J, Li XG. Trifluoperazine, a novel autophagy inhibitor, increases radiosensitivity in glioblastoma by impairing homologous recombination. J Exp Clin Cancer Res 36(1):118, 2017. doi:10.1186/s13046-017-0588-z. 
  28. Talasila KM, Røsland G, Hagland H, Eskilsson E, Tran GT, Fritah S, Azuaje F, Atai N, Harter P, Mittelbronn M, Anderson M, van Noorden R, Niclou SP, Thorsen F, Tronstad KJ, Tzoulis C, Bjerkvig R, Miletic H. The angiogenic switch leads to a metabolic switch in human glioblastoma. Neuro-Oncol Sep 19(3):383-393, 2017. 
  29. Ilhan-Mutlu A, Osswald M, Liao Y, Gömmel M, Reck M, Miles D, Mariani P, Gianni L, Lutiger B, Nendel V, Srock S, Perez-Moreno P, Thorsen F, von Baumgarten L, Preusser M, Wick W, Winkler F. Bevacizumab prevents brain metastases formation in lung adenocarcinoma. Mol Cancer Ther Jan 25, 15(4):702-710, 2016. 
  30. Aasen SN, Pospisilova A, Eichler T, Panek J, Hruby M, Stepanek P, Spriet E, Jirak D, Skaftnesmo KO, Thorsen F. A novel nanoprobe for visualisation of melanoma metastatic cells by fluorescence and MRI. Int J Mol Sci 16:21658-21680, 2015.
  31. Sundstrøm T, Espedal H, Harter P, Fasmer KE, Skaftnesmo KO, Horn S, Hodneland E, Mittelbronn M, Weide B, Beschorner R, Bendner B, Rygh CB, Lund-Johansen M, Bjerkvig R, Thorsen F. Melanoma brain metastasis is independent on LDHA expression. Neuro-Oncol 17:1374-1385, 2015. 
  32. Keunen O, Taxt T, Tonn JC, Grüner R, Lund-Johansen M, Pavlin T, Bjerkvig R, Niclou S, Thorsen F. Multimodal imaging of gliomas in the context of cellular and molecular therapies. Adv Drug Deliv Rev 76:98-115, 2014. 
  33. Rygh, CB, Wang J, Thuen M, Gras-Navarro A, Huuse EM, Thorsen F, Poli A, Zimmer J, Haraldseth O, Lie SA, Enger PØ, Chekenya M. Dynamic contrast enhanced MRI detects early response to adoptive NK cellular immunotherapy targeting the NG2 proteoglycan in a rat model of glioblastoma. PLoS ONE 2014 9(9):e108414.
  34. Daphu I, Horn S, Stieber D, Varughese J, Skaftnesmo KO, Bjerkvig R, Thorsen F. In vitro treatment of melanoma brain metastasis by simultaneously targeting the MAPK and PI3K signaling pathways. Int J Mol Sci 15:8773-8794, 2014.
  35. Qin SP, Fite BZ, Gagnon KG, Seo JW, Curry F, Thorsen F, Ferrara KW. A physiological perspective on the use of imaging to assess the in vivo delivery of therapeutics. Ann Biomed Eng 42(2):280-298, 2014.
  36. Thorsen F, Fite B, Mahakian L, Seo JW, Qin SP, Harrison V, Johnson S, Ingham E, Meade T, Caskey C, Sundstrøm T, Meade T, Harter PN, Skaftnesmo KO, Ferrara KW. Multimodal imaging enables early detection and characterization of changes in tumor permeability of brain metastases. J Control Rel 172:812-822, 2013. 
  37. Poli A, Wang J, Domingues O, Planagumá J, Yan T, Rygh CB, Skaftnesmo KO, Thorsen F, McCormack E, Hentges F, Pedersen PH, Zimmer J, Enger PO, Chekenya M. Targeting glioblastoma with NK-cells and mAb against NG2/CSPG4 prolongs animal survival. Oncotarget 4(9):1527-1546, 2013. 
  38. Lillefosse HH, Tastesen HS, Du ZY, Ditlev DB, Thorsen F, Madsen L, Kristiansen K, Liaset B. Hydrolyzed casein reduces diet-induced obesity in male C57BL/6J mice. J Nutr 143(9):1367-1375, 2013.
  39. Sundstrøm T,  Daphu I, Wendelbo I, Hodneland E, Lundervoll A, Immervoll H, Skaftnesmo KO, Babic M, Jendelova P, Sykova E, Lund-Johansen M, Bjerkvig R, Thorsen F. Quantitative tracking of nanoparticle labeled melanoma cells improves the predictive power of an experimental brain metastasis model. Cancer Res 73(8):2445-2456, 2013. 
  40. Daphu I, Sundstrøm T, Huszthy PC, Niclou SP, Sakariassen P, Immervoll H, Miletic H, Bjerkvig R, Thorsen F. In vivo animal models for studying brain metastasis: value and limitations. Clin Exp Metastasis 30:695-710, 2013.
Kompetanse

Forskningsveiledning:

2016-2021 Hovedveileder for 3 Post Docs.

2014-2021 Hovedveileder for 9 studenter i Forskerlinjeprogrammet, UiB.

2005-2021 Veileder for 13 PhD studenter (7 som hovedveileder).

1996-2021 Veileder for 16 Master studenter (hovedveileder).

Arbeidserfaring:

1989-1995 Haukeland Sykehus. Medisinsk Fysiker, Overingeniør.

1991-1994 Timelærer i Apparatlære, Radiografhøgskolen i Bergen.

1993-2006 Elekta Instrument AB. Medisinsk konsulent.

1995- 1998 Universitetet i Bergen. Stipendiat.

1998-2004 Haukeland Universitetssykehus. Medisinsk Fysiker, Sjefingeniør.    

2000-2002 Institutt for Anatomi og Cellebiologi. Forsker (Post. doc.).                    

2004-2008 UNIFOB AS. Vitenskapelig Prosjektleder. 

2008-2010 Institutt for Biomedisin, UiB. Førsteamanuensis.

2010-2023 Institutt for Biomedisin, UiB. Professor.

2019-2021 Shandong University, Jinan, Kina. Professor.                             

Utdannelse:

1989 Cand Mag i fysikk, matematikk og data, Universitetet i Trondheim.

1989 Cand Scient i biofysikk, Universitetet i Trondheim.

1998 Dr Scient, Institutt for Anatomi og Cellebiologi, Universitetet i Bergen.

Kurs:

1990 Bedriftspedagogisk senter. Presentasjonsteknikk og kommunikasjon.  

1994 Elektrisitetstilsynet. Godkjenning for å reparere elektromedisinsk utstyr.

1998 Hewlett Packard, Oslo. Sluttbrukerkurs i Unix operativsystem.

1998 Universitetet i Bergen. Påbyggingsseminarer i forsøksdyrlære.

1999 Haukeland Sykehus. Prosjektledelse.

2000 Advanced Visualization System. Introduksjon i AVS programmering.

2004 Hyperion Ltd (Ressurssenteret,Bergen). How to negotiate, manage, administer and finish an EU Contract.

2006 Psykologisk Fakultet, UiB. Basismodul i universitetespedagogikk.

2007 Psykologisk Fakultet, UiB. Forskningsveiledning.

2007-09 UNIFOB AS, Bergen. Utviklingsprogram for Forskningsledere.

2018 UiB PhD-veileder kurs bestått 31.07.2018.

2018  Begynnerkurs i Kinesisk-Mandarin (Mandarin nivå A1, del 1 og 2).