C.A. Spek PhD

foto

C.A. Spek PhD

Position
Research Associate
Main activities
Research
Specialisation
Protease activated receptor signaling in pathophysiology
Focus of research
  • Blood coagulation-driven Protease Activated Receptor signaling in pathophysiology.
  • Role of Protease Activated Receptors in pulmonary fibrosis.
  • Relationship between blood coagulation and pancreatic cancer.
  • C/EBPdelta: master regulator of pancreatic cancer progression.

 

Key publications
  • Duitman Janwillem, Schouten Marcel, Groot Angelique P., Daalhuisen Joost B., Florquin Sandrine, van der Poll Tom, Spek C. Arnold CCAAT/enhancer-binding protein delta facilitates bacterial dissemination during pneumococcal pneumonia in a platelet-activating factor receptor-dependent manner Proceedings of the National Academy of Sciences of the United States of America 2012;109 (23):9113-9118 [PubMed]
  • Klümpen Heinz-Josef, Queiroz Karla C. S., Spek C. Arnold, van Noesel Carel J. M., Brink Helmy C., de Leng Wendy W. J., de Wilde Roeland F., Mathus-Vliegen Elisabeth M. H., Offerhaus G. Johan A., Alleman Maarten A., Westermann Anneke M., Richel Dirk J. mTOR inhibitor treatment of pancreatic cancer in a patient With Peutz-Jeghers syndrome Journal of clinical oncology 2011;29 (6):e150-e153 [PubMed]
  • Lin Cong, von der Thüsen Jan, van der Poll Tom, Borensztajn Keren, Spek C. Arnold Increased Mortality during Bleomycin-induced Pulmonary Fibrosis due to Low Endogenous Activated Protein C Levels American journal of respiratory and critical care medicine 2015;192 (10):1257-1259 [PubMed]
  • Lin Cong, Duitman Janwillem, Daalhuisen Joost, ten Brink Marieke, von der Thüsen Jan, van der Poll Tom, Borensztajn Keren, Spek C. Arnold Targeting protease activated receptor-1 with P1pal-12 limits bleomycin-induced pulmonary fibrosis Thorax 2014;69 (2):152-160 [PubMed]
  • Shi Kun, Queiroz Karla C. S., Roelofs Joris J. T. H., van Noesel Carel J. M., Richel Dirk J., Spek C. Arnold Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model Journal of pathology 2014;234 (3):398-409 [PubMed]
All Publications
Curriculum Vitae

Education/training:

- Master’s Molecular Biology at Rijksuniversiteit Leiden, 1992

- Doctorate on Protein C gene transcription at Rijksuniversiteit Leiden, 1998

 

Positions and employment

- Associate Professor Molecular Medicine, Academic Medical Center, Amsterdam, Center for Experimental and Molecular Medicine (1 January 2007 - Permanent)

- Staff member Blood coagulation, Academic Medical Center, Amsterdam, Center for Experimental and Molecular Medicine (1 May 2002 – 31 December 2006)

- Post-Doc position: Blood coagulation factors and its relevance in inflammatory disease, Academic Medical Center, Amsterdam, Experimental Internal Medicine (1 May 2000 – 30 April 2002)

- Post-Doc position: “Tissue factor” induced, localized arterial thrombosis in transgenic mice (Project on a personal scholarship funded by the E. Dekker program of the Dutch Heart Foundation), Academic Medical Center, Amsterdam, Experimental Internal Medicine  (1 May 1997 – 30 April 2000)

- PHD studies: Characterization of the human protein C   gene promoter, Academic Hospital Leiden, Haemostasis en Thrombosis Research Centre, Leiden University (1 December 1992 - 1 February 1997)

 

Peer Review

- Manuscript reviewer for (among others) Blood, Thrombosis and Haemostasis, Clinical cancer research, Plos One, Critical Care medicine and Journal of Thrombosis and Haemostasis.

- Grant reviewer for (among others) the Netherlands Heart Society, the French National Research Agency, the Netherlands Organisation for Scientific Research (NWO), the Austrian Academy of sciences, the Dutch cancer Society (KWF) and the Dutch Thrombosis Foundation.

 

Memberships and commitees

- Member of the committee of approval of the thesis of Dr Melissa Uil (University of Amsterdam, 2020), Dr Meng Li (Erasmus University Rotterdam, 2020), Dr Butul Unlu (Leiden University, 2019), Dr Ishaku Adamu (Erasmus University Rotterdam, 2018), Dr Christiaan Tieken (Leiden University, 2017), Dr Juan Li (Erasmus University Rotterdam, 2017), Dr Lionel Lattenist (University of Amsterdam, 2016), Dr Kan Chen (Erasmus University Rotterdam, 2016), Dr Yascha van den Berg (Leiden University, 2013), Dr Monireh Dashti (Erasmus University Rotterdam, 2012), Dr G Stokman (University of Amsterdam, 2008) and Dr Martins Cavagis (Groningen University, 2006).

- Member of the International Society of Thrombosis and Haemostasis, the European Association for the study of Diabetes and the American Thoracic Society.

- Editorial Board member of the Journal of Clinical and Translational Research (2015-present)

- Member of the International Scientific Advisory Board of the ISTH Congress 2009 and 2013.

- Editorial Board member of ‘Thrombosis’ (2009-present).

- Member of the 2008 Advisory board of the Journal of Thrombosis and Haemostasis.

- Member of the 'Thrombosis and Haemostasis' committee of the Dutch Heart Foundation (2008-2014).

 

Other academic activities

- ​​​​​​​PhD (co)supervisor of Dr Maaike Waasdorp (thesis defense 2019), Dr Kun Shi (thesis defense 2015), Dr Cong Lin (thesis defense 2015), Dr JanWillem Duitman (thesis defense 2014), Dr Geerte van Sluis (thesis defense 2010), Dr keren Borensztajn (thesis defense 2009), Dr Karla de Souza Queiriz (thesis defense 2008), Dr Tatjana Niers (thesis defense 2008), Dr Martijn de Kruif (thesis defense 2008), Dr Maarten Bijlsma (thesis defense 2008), Dr Lois Bruggemann (thesis defense 2008), Dr Sjoukje Slofstra (thesis defense 2007) and Dr Saskia Schoenmakers (thesis defense 2004).

- Educational experience: Development and supervising of a DNA course for medical students and lecturer for (medical) students.

- Establishing a highly productive cooperation with MRC Holland in order to develop a quantitative mRNA assay specific for inflammatory and apoptotic mediators (MLPA).

 

Media attention

- Researcher of the week of the Dutch Cancer Society (https://www.kwf.nl/onderzoek/dit-onderzoek-maken-we-mogelijk/onderzoeker-van-de-week-arnold-spek.

- Vlog for volunteers of the Mont Ventoux challenge 2019 ('you climb the mountain to support research on targeted therapy for pancreatic cancer').

 

Patent applications

- Inventor on Patent 100-088-78: A pharmaceutical composition suitable for the treatment of cancer and method of preparing said pharmaceutical composition.

- Inventor on Patent EP2539448A4: Protein C Zymogen and Methods of Use Thereof to Prevent Cancer Metastases.

 

 

 

Research programmes

C.A. Spek PhD (Protease activated receptor signaling in pathophysiology.)

My research focusses on the biology underlying the dismal prognosis of pancreatic cancer and idiopathic pulmonary fibrosis. Both disorders are characterized by excessive proliferation, immune cell infiltration and extracellular matrix production. We aim to understand the cross-talk between the different cellular components in driving disease progression in order to identify alternative targets to combat disease progression. In KWF funded projects, we specifically study the role of the coagulation – protease activated receptor axis in tumor growth and drug resistance whereas a NWO funded project focusses on this specific axis in idiopathic pulmonary fibrosis. Finally, we recently started to explore the feasibility and efficacy of protease-mediated drug release as potential novel targeted therapy in pancreatic cancer. In this KWF funded project, we address the hypothesis that protease-mediated drug release allows efficient drug delivery to pancreatic tumors thereby specifically killing cancer cells with reduced cytotoxicity towards non-cancerous tissue.

Postdocs
J.W. Duitman PhD

Others
H.L. Aberson BEng
M. El Mandili

Current research funding
  • AMC
  • KWF Kankerbestrijding
  • ZonMw (Vrijgesteld)