Jonas Fuxe Group
Jonas Fuxe's profile page.
Mechanisms of Tissue Remodeling in Inflammation and Cancer
A fundamental principle of multi-cellular organisms is the ability of cells to interact and communicate. Tubular organs are lined by epithelial and endothelial cells that form selective barriers allowing the formation of different tissue compartments. This function is dependent on the ability of cells to polarize and establish specialized intercellular junctions that regulate flux of ions, solutes and cells across the barrier. The assembly and disassembly of these junctions is tightly regulated during development and in normal physiology, but is disturbed in pathological conditions of tissue remodeling, such as in chronic inflammation and cancer. We use a combination of in vitro studies and mouse models of chronic airway inflammation and cancer to study the role of specific growth factors and cytokines in mediating tissue remodeling and junction reorganization in endothelial and epithelial cell layers.
A major research theme in the lab is remodeling of blood and lymphatic vessels. While VEGF is a major angiogenic factor, less is known about the mechanisms that drive other types of vascular remodeling including phenotypic switches of endothelial cells leading to excessive infiltration of inflammatory cells. We are particularly interested in the role of angiopoietins and the Tie2 signaling pathway in modulating the inflammatory response by acting on blood and lymphatic vessels.
Another theme is the role of epithelial-mesenchymal transition (EMT) in tumor cell invasion and epithelial remodeling in chronic inflammation. EMT is characterized by loss of cell-cell adhesion and polarity accompanied by cytoskeletal rearrangements and increased cell motility. TGF-b is a major inducer of EMT but the molecular mechanisms involved are not clear. We are interested in transcriptional regulation of target genes downstream of the TGF-b/Smad signaling pathway.
Postdoc: Vacant position(s)
Mei-Fong Pang, PhD. PhD student in Fuxe group 2009-2012. Current position: postdoc at Princeton University, US.
Jill Johnson, PhD. Postdoc in Fuxe group 2008-2011. Current position: Research Fellow at the National Heart and Lung Institute, Imperial College London
Tove Berg, PhD. Postdoc in Fuxe group 2009-2012.
Vedrana Tabor, PhD. Postdoc in Fuxe group 2012-2014.
Sandra Travica, PhD. Postdoc in Fuxe group 2013-2014. Current position: Medical Scientific Advisor for Oncology Business at Pfizer Inc.
Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking aVb8-TGFb signaling in the brain.
Arnold DA, Niaudet C, Pang M-F, Siegenthaler J, Gaengel K, Jung B, Ferrero GM,
Mukouyama Y-S, Fuxe J, Akhurst R, Betsholtz C, Sheppard D, Reichardt LF.
Development. 2014 Dec 141;4489-4499.
C/EBPb expression is an independent predictor of overall survival in breast cancer patients by
MHCII/CD4-dependent mechanism of metastasis formation.
Kurzejamska E, Johansson J, Jirström K, Prakash V, Ananthaseshan S, Boon L, Fuxe J,
Oncogenesis. 2014 Nov 3;3:e125
Epithelial-mesenchymal transition: A link between cancer and inflammation.
Fuxe J and Karlsson MCI.
Book chapter in “CANCER AND INFLAMMATION MECHANISMS: Chemical, Biological, and Clinical Aspects”. 2014 p23-39 (Wiley).
MiR-155-mediated loss of C/EBPb shifts the TGF-b response from growth inhibition to
epithelial-mesenchymal transition, invasion and metastasis in breast cancer.
Johansson J, Berg T, Kurzejamska E, Pang MF, Tabor V, Jansson M, Roswall P, Pietras K,
Sund M, Religa P, Fuxe J.
Oncogene. 2013 Dec 12;32(50):5614-24
Human enteroviruses in ileocaekal Crohn’s disease.
Nyström N, Skoog O, Berg T, Hansson I, Frisk G, Gyllensten U, Finkel Y, Fuxe J#, Wanders A#.
Clin Transl Gastroenterol. 2013 Jun 27;4:e38.
Deficiency for endoglin in tumor vasculature weakens the endothelial barrier to metastatic
Anderberg C, Cunha SI, Zhai Z, Cortez E, Pardali E, Johnson JR, Franco M, Páez-Ribes M,
Cordiner R, Fuxe J, Johansson BR, Goumans MJ, Casanovas O, Ten Dijke P, Arthur HM, Pietras K.
J Exp Med. 2013 Feb 11.
TGF-b-induced epithelial-mesenchymal transition: A link between cancer and inflammation.
Fuxe J and Karlsson MCI.
Semin Cancer Biol. 2012. Oct;22(5-6):455-61.
The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2.
Gaengel K, Niaudet C, Hagikura K, Siemsen BL, Muhl L, Hofmann JJ, Ebarasi L, Nyström S,
Rymo S, Chen LL, Pang MF, Jin Y, Raschperger E, Roswall P, Schulte D, Benedito R,
Larsson J, Hellström M, Fuxe J, Uhlén P, Adams R, Jakobsson L, Majumdar A, Vestweber
D, Uv A, Betsholtz C.
Dev Cell. 2012 Sep 11;23(3):587-99.
Repeated cisplatin treatment can lead to a multiresistant tumor cell population with stem cell
features and sensitivity to 3-bromopyruvate.
Wintzell M, Löfstedt L, Johansson J, Pedersen AB, Fuxe J, Shoshan M.
Cancer Biol Ther.
2012 Sep 6;13(14).
Essential role of the Coxsackie - and Adenovirus Receptor (CAR) in development of the
lymphatic system in mice.
Mirza M#, Pang M-F#, Zaini MA, Haiko P, Tammela T, Alitalo K, Philipson L, Fuxe J, and
PLoS One. 2012;7(5):e37523.
EMT research – not an empty promise.
International Innovation, NordicFocus, September 2012;27-33
Pericyte requirement for anti-leak action of angiopoietin-1 and vascular remodeling in
Fuxe J#, Tabruyn SP#, Colton K, Zaid H, Lashnits E, Morisada T, Le T, O'Brien S, Epstein
DM, Koh GY and McDonald DM.
Am J Pathol. 2011 June;178(6):2897-909.
Chronic respiratory aeroallergen exposure in mice induces epithelial-mesenchymal transition
in the large airways.
Johnson JR, Roos A, Berg T, Nord M and Fuxe J.
PLoS One. 2011 Jan 20;6(1):e16175.
Blogg for Mustaschkampen (Cancerfonden) Bloggomaten Kontanten/Facebook
Fuxe J. 2011.
“Den dagen var jag riktigt nöjd”.
Article in Cancerfonden. 2011.
Transcriptional crosstalk between TGF-b and stem cell pathways in tumor cell invasion: Role
of EMT promoting Smad complexes
Fuxe J, Vincent T, Herreros AGdH.
Cell Cycle, 2010 Jun 12;9(12).
Angiopoietin-2 driven vascular remodeling in airway inflammation.
Tabruyn SP, Colton K, Morisada T, Fuxe J, Wiegand SJ, Thurston G, Coyle AJ, Connor J,
and McDonald DM.
Am J Pathol. 2010 Dec;177(6):3233-43.
Angiopoietin/Tie2 signaling transforms capillaries into venules primed for leukocyte
trafficking in airway inflammation.
Fuxe J, Lashnits E, O'Brien S, Baluk P, Tabruyn SP, Kuhnert F, Kuo C, Thurston G and
Am J Pathol. 2010 Apr;176(4):2009-18.
“Coming to America: Doing a postdoc in the U.S”.
Science Careers 2010
Estrogen receptor-beta expression in human laryngeal carcinoma: Correlation with the
expression of epithelial-mesenchymal specific biomarkers.
Goulioumis AK, Fuxe J, Varakis J, Repanti M, Goumas P and Papadaki H.
Oncol Rep. 2009 Nov;22(5):1063-8.
A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition.
Nat. Cell Biol. 2009 Aug;11(8):943-50
Ny upptäckt kan leda till terapi mot metastaser.
Vincent T and Fuxe J.
Onkologi i Sverige. 2009 6:20-24
Svenskar har hittat protein som sprider cancer.
Barncancerfonden in 2009.
“Unga forskare vill förbättra behandlingen”,
Barn och Cancer, 2008.
Functionally specialized junctions between endothelial cells of lymphatic vessels.
J. Exp. Med. 2007 Oct;204(10):2349-62
Induction of neutrophil gelatinase-associated lipocalin in vascular injury via activation of
Bu DX, Hemdahl AL, Gabrielsen A, Fuxe J, Zhu C, Eriksson P, Yan ZQ.
Am J Pathol. 2006 Dec;169(6):2245-53.
The coxsackie- and adenovirus receptor (CAR) is an in vivo marker for epithelial tight junctions, with a potential role in regulating permeability and tissue homeostasis.
Exp. Cell Res. 2006 May;312(9):1566-80
CLMP, a novel member of the CTX family and a new component of epithelial tight junctions.
J. Biol. Chem. 2004 Jan;279(1):796-804
Immortalization of bovine capillary endothelial cells by hTERT alone involves inactivation of endogenous p16INK4A/pRb.
FASEB J. 2003 Apr;17(6):764-6
Expression of the coxsackie and adenovirus receptor in human astrocytic tumors and xenografts.
Int. J. Cancer 2003 Mar;103(6):723-9