Fibroblasts in the progression of gastrointestinal diseases

The current focus of our research team is on understanding how fibroblasts influence gastrointestinal disease progression (Inflammatory bowel diseases and gastrointestinal cancers) and to develop the best near-patient models to study this. My current group is composed of 6 PhD students, 2 post-doc researchers and 4 technicians. Because of the close interaction between clinicians and basic researchers, one of the strengths of my group is the combined analysis of clinical samples with in-depth mechanistic studies in vitro using 3D patient-derived multicellular models and advanced animal models.

Our work has been supported by grants from the Dutch Cancer society/ Alpe d’HuZes, Stichting Fonds Oncologie Holland (SFOH), Stichting Sacha Swarttouw-Hijmans, Tracon Pharmaceuticals, Agentschap voor innoveren en onderzoeken (VLAIO) and the European Crohn and Colitis organisation (ECCO). 

A summary for layman (samenvatting voor niet-wetenschappers) can be found here.

Biosketch:

After obtaining his Master’s degree in Biopharmaceutical Sciences (2003), a strongly research-focused education, Luuk performed a translational research project at the Gastroenterology department of the LUMC. He focused on the interplay between tumour cells and the tumour stroma, unravelling its role in CRC progression and metastasis. This was the start of his continued research interest in how fibroblasts interact with other cells in their environment and how they can influence tumour progression.

Following his PhD defense (2009), he joined the ten Dijke group (Molecular Cell Biology), where he gained extensive knowledge on the role of the TGF-β receptors endoglin and ALK1. This position resulted in 3 key first author publications on the identification of MMP14 as the endoglin shedding protease (Cancer Res 2010), the intriguing interplay between epithelial tumour cells and CAFs in CRC progression (Oncogene 2014) and targeting of ALK1 in tumour angiogenesis (Clin Cancer Res 2016).

In the course of this post-doc project he started extending my own independent research line, for which he was awarded the Alpe d’HuZes Bas Mulder Award in 2011. This project focused on how the endoglin-dependent interaction between cancer cells and CAFs influences metastatic spread of tumours and resulted in 2 important publications in Oncogene (2016) and Clinical Cancer Research (2018).

In 2015 his group moved to the Gastroenterology and hepatology department, who have appointed him as assistant professor in 2016. This position enabled me to expand my research on fibroblasts into inflammatory bowel diseases. In January 2018 I was appointed as head of the research laboratory gastroenterology-hepatology and in June 2019 as associate professor. 

Post doctoral researchers: 

Marieke Barnhoorn

Marten Hornsveld

PhD students ongoing:

Sarah Ouahoud

Mark Schoonderwoerd 

Sarah Hakuno

Tom Harrijvan

Richard Dang

Zhou Zhou  

PhD students completed and former lab members:

Dr. Marieke Barnhoorn (2020)

https://scholarlypublications.universiteitleiden.nl/handle/1887/136912

Dr. Ramona Bruckner (2019-2020)

https://www.ecco-ibd.eu/publications/ecco-news/item/ecco-fellowship-study-synopsis-bruckner.html

Dr. Madelon Paauwe (2017) 
https://openaccess.leidenuniv.nl/bitstream/handle/1887/45876/front.pdf?sequence=3  

Internships:

We always have research projects available for bachelor and master students with (bio-)medical and biopharmaceutical background. Please contact us via: L.J.A.C.Hawinkels@LUMC.nl or +31 71 526 6736      

More information:

LinkedIn

ORCID

Researchgate


Selected publications: 

Schoonderwoerd MJ, Koops MF, Angela RA, Koolmoes B, Toitou M, Paauwe M, Barnhoorn MC, Liu Y, Sier CF, Hardwick JC, Nixon AB, Theuer CP, Fransen MF, Hawinkels LJ. “Targeting Endoglin-Expressing Regulatory T Cells in the Tumor Microenvironment Enhances the Effect of PD1 Checkpoint Inhibitor Immunotherapy” Clin Cancer Res. 2020 Jul 15;26(14):3831-3842. Link

Ouahoud S, Hardwick JCH, Hawinkels LJ. "Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment” Int J Mol Sci. 2020 May 29;21(11):3888. Link

Barnhoorn MC, Hakuno SK, Bruckner RS, Rogler G, Hawinkels LJ, Scharl M. “Stromal Cells in the pathogenesis of Inflammatory Bowel Disease” J Crohns Colitis. 2020 Mar 11:jjaa009. Link

Schoonderwoerd MJ, Goumans MJ, Hawinkels LJ. "Endoglin: Beyond the Endothelium” Biomolecules. 2020 Feb 12;10(2):289. Link

Paauwe M, Heijkants RC, Oudt CH, van Pelt GW, Cui C,  Theuer CP, Hardwick JC, Sier CF,  Hawinkels LJ Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer Oncogene 2016 Aug 4;35(31):4069-79. Link

Hawinkels L*, Garcia de Vinuesa A*, Paauwe M, Kruithof-de Julio M, Soullié T, Wiercinska E, Pardali E, Mezzanotte L, Keereweer S, Braumuller T, Heijkants R, Jonkers J, Löwik C,  Goumans MJ1, ten Hagen T and ten Dijke P Activin Receptor-like Kinase 1 Ligand Trap Reduces Microvascular Density and Improves Chemotherapy efficiency to Various Solid Tumors. Clin Cancer Res. 2016 Jan 1;22(1):96-106.Sep 15. pii: clincanres.0743.2015. [Epub ahead of print]. Link

Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE, IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015 Jun 18;522(7556):345-8. Link

Hawinkels LJ, Paauwe M, Verspaget HW, Wiercinska E, van der Zon JM, van der Ploeg K, Koelink PJ, Lindeman JH, Mesker W, ten Dijke P, Sier CF. Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts. Oncogene. 2014 Jan 2;33(1):97-107. Link


Hawinkels LJ, Garcia de Vinuesa A, Ten Dijke P. Activin receptor-like kinase 1 as a target for anti-angiogenesis therapy. Expert Opin Investig Drugs. 2013 Nov;22(11):1371-83.Epub 2013 Sep 21. Review. Link 

Paauwe M, ten Dijke P, Hawinkels LJ Endoglin for tumor imaging and targeted cancer therapy. Expert Opin Ther Targets. 2013 Apr;17(4):421-35. Epub 2013 Jan 17. Review. Link

Hawinkels LJ, Ten Dijke P. Exploring anti-TGF-β therapies in cancer and fibrosis. Growth Factors. 2011 Aug;29(4):140-52. Epub 2011 Jun 30. Review. Link

Hawinkels LJ, Kuiper P, Wiercinska E, Verspaget HW, Liu Z, Pardali E, Sier CF, ten Dijke P Matrix metalloproteinase-14 (MT1-MMP)-mediated endoglin shedding inhibits tumor angiogenesis. Cancer Res. 2010 May 15;70(10):4141-50. Epub 2010 Apr 27. Link

Hawinkels LJ, Zuidwijk K, Verspaget HW, de Jonge-Muller ES, van Duijn W, Ferreira V, Fontijn RD, David G, Hommes DW, Lamers CB, Sier CF  VEGF release by MMP-9 mediated heparan sulphate cleavage induces colorectal cancer angiogenesis. Eur J Cancer. 2008 Sep;44(13):1904-13.Epub 2008 Aug 6. Link