Prof. E. Lutgens PhD

All Publications

CURRICULUM VITAE
Date prepared: 220212

PART I: GENERAL INFORMATION
A: Personalia
Name: Esther Lutgens
Place of Birth: Heerlen, The Netherlands
Date of Birth: 4th of November, 1975
Sex: Female
Nationality: Dutch

 

Phone: +31-(0)20-5666762
Email: E.lutgens@amc.uva.nl

Education
1988-1994 Gymnasium, Katholiek Gymnasium Rolduc, Kerkrade, The Netherlands.
1994-2001 Medicine; University of Maastricht, the Netherlands
1996-2001 PhD Pathology; Dept. of Pathology, faculty of Medicine, Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, The Netherlands.
2003-2007 Specialty training Pathology, Prof. M. Daemen, University Hospital Maastricht, The Netherlands.

Additional Pre-doctoral training
1998 Research at Biogen Inc., Cambridge, MA, USA (3 months).
1998 Research in the Howard Hughes Institute of Immunobiology, (dr. RA. Flavell), Yale Medical School, New Haven, CT, USA (3 months).
1999 Research in the Center for Transgene Technology and Gene Therapy, KU Leuven, Belgium, lab of Prof. dr. P. Carmeliet and Prof. dr. D. Collen (5 months).

Post-doctoral Training
2001-2006 Post-doctoral research fellow, the dept. of Pathology, University of Maastricht.
2002 Post-doctoral research fellow, dept vascular medicine, Prof. P. Libby, Harvard Medical School, Boston, MA, USA.
2002-2003 Angiogenesis Research Centre, Prof. M. Simons and dept of microbiology/immunology, Prof. R. Noelle, Dartmouth Medical School, Hanover, NH, USA.

Academic Appointments
2006- 2008 Assistant Professor, dept of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands.
2008-2011 Associate Professor, dept of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands.
2009-2011 Part-time appointment as W2 Professor, IMCAR, RWTH Aachen, Germany.
2011-now Full Professor, dept of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, the Netherlands.
2011-now Visiting W2 Professor, IPEK, LMU, Munich, Germany.
Oct2011-now Associate Professor, dept of Medical Biochemistry, Academic Medical Center, University of Amsterdam, the Netherlands.

B. Major Committee Assignments
International
- Grant reviewer: FWO (Fund for Scientific Research, Flanders, Belgium)
- Grant reviewer: Expert Review KU Leuven
- Grant reviewer: SNF (Swiss National Science Foundation)
- Grant reviewer: FNR Luxemburg
- External review committee, Cardiovascular Medicine, Karolinska Institute, Sweden (2011)

National
- Grant reviewer project grants Netherlands Heart Foundation (NHS)
- Grant reviewer Dr. E. Dekker program (NHS)
- Grant reviewer Innovation Fellowship applications (VENI and VIDI grants), The Netherlands Foundation of Health Research and Development (ZonMW).
- Grant reviewer Programma Translationeel Onderzoek, ZonMW.
- PhD thesis evaluation committee:
o Eugene Tkachenko, Maastricht University, 2005
o Lenneke Prinzen, Maastricht University, 2009
o Valerie Croons, University of Antwerp, 2009
o Melissa Swinnen, Maastricht University, 2010
o Liselotte Kornman, Maastricht University, 2010
o Isabelle Daissermont, Maastricht University, 2011
o Julian Borisshof, Maastricht University, 2011
o J. Sipkens, Free University, Amsterdam, 2011
o D. Johansson, Karolinska Institute, Stockholm, Sweden, 2012

C. Professional Societies
- Professional member of the American Heart Foundation (AHA).
- Council member of the ‘Arteriosclerosis Thrombosis and Vascular Biology’ council (AHA).
- Member of the ‘North America Vascular Biology Organization’ (NAVBO).
- Member of the Dutch Atherosclerosis Society (DAS).
- Member of the ‘European Vascular Genomics Network’ (EVGN) (FP6).
- Member of the ‘European Vascular Biology Organization’ (EVBO).

D. Editorial Boards
- Ad hoc reviewer for: Circulation, Circulation Research, Arteriosclerosis Thrombosis and Vascular Biology, Stroke, Atherosclerosis, Journal of Immunology, Journal of Pathology, American Journal of Pathology, Thrombosis and Haemostasis, Diabetologica, Cardiovascular Research, Vascular Pharmacology Journal.
- Editorial Board member for Arteriosclerosis Thrombosis and Vascular Biology (2009-now).
- Guest editor Thrombosis and Haemostasis (2011-now)
- Editor theme issue Thrombosis and Haemostasis (nov 2011); immunology of cardiovascular disease.
- Editorial Board member for ‘Journal of Molecular Medicine’ (2011-now).
- Editorial Board member for ‘PLOS one’ (2011-now).

E. Awards and Honours
1999 Young Investigator Award, 6th Joint Meeting of the Belgian and Dutch Working Groups on Invasive Cardiology, Maastricht, the Netherlands.
1999 Dr. E. Dekker student-grant, the Netherlands Heart Foundation. Research in the Center for Transgene Technology and Gene Therapy, KU Leuven, Prof. dr. P. Carmeliet and Prof. dr. D. Collen, KU Leuven, Belgium.
1999 Young Investigator Award International Society for Heart Research, XXth European Section Meeting, Maastricht, the Netherlands.
1999 Prize for Best Hot Topic Presentation, 4th annual meeting of the European Council for Blood Pressure and Cardiovascular Research (ECCR), Noordwijkerhout, the Netherlands.
2000 New Investigator Travel Award, First Conference on Arteriosclerosis, Thrombosis and Vascular Biology. Denver, Co, USA.
2000 EVBA Fellowship, XIth international Vascular Biology Meeting, Geneva, Switzerland.
2000 Vasculaire Biology prijs 1999/2000, Parke Davis, Amsterdam, the Netherlands.
2000 Dr. E. Dekker post-doctoral fellowship, Dutch Heart Foundation.
2002 TALENT-stipendium Netherlands Research organization (NWO).
2002 Fellowship Dutch Atherosclerosis Society (DAS).
2002 Finalist Irvine Page young Investigator award. Third conference on Arteriosclerosis, Thrombosis and Vascular Biology, Salt Lake City, Ut, USA.
2003 VENI laureate, Netherlands Foundation for Health Research and development (ZonMW), Innovational Research Incentives Scheme.
2003 Winner of the Second James T. Willerson Vulnerable Plaque Young investigator award for basic research, Chicago, IL, USA.
2003 Winner of the SNS-bank thesis prize, Maastricht, the Netherlands.
2003 American Heart Association Council on Arteriosclerosis, Thrombosis and Vascular Biology’s Merit Award for Young Investigators, Scientific Sessions of the American Heart Association, Orlando, Fl, USA.
2007 VIDI laureate, Netherlands Foundation for Health Research and development (ZonMW), Innovational Research Incentives Scheme.
2007 ASPASIA laureate, Netherlands Foundation for Health Research and development (ZonMW), Innovational Research Incentives Scheme.
2008 Sofja Kovalevskaja laureate, Humboldt Stiftung, Germany.
2009 Established Investigator, Dr. E. Dekker program, Dutch Heart Foundation.
2011 Jubileumprijs Landelijk Netwerk Vrouwelijke Hoogleraren (LnvH), 6 Okt, Utrecht.

F. Additional Training, Linguistic Skills
- Licensed under Dutch Law for Health Care and Experimental Usage of Laboratory Animals (University of Maastricht, the Netherlands).
- Licensed under US Law for Health Care and Experimental Usage of Laboratory Animals (Harvard Medical School, Boston, MA, USA).
- Site-specific Certified Radiation worker (Harvard Medical School, Boston, MA, USA).
- BIG registration 2001, licensed MD.

Full oral and written command of Dutch, English and German.

G. Research Interests as an Independent Investigator
Inhibition of CD154/CD40 interactions turned out to be one of the most potent plaque stabilizing strategies known. However, CD154, as it is part of the family of co-stimulatory molecules, plays a central role in modulating and regulating immune responses, both in lymphoid organs and in (diseased) tissues. Therefore, long-term inhibition of CD154, which is required for a chronic disease like atherosclerosis, would unbalance the patient’s immune system and cause severe side effects.
As a post-doc, my research interests focused on the mechanisms of the effects of modulation of co-stimulatory molecules on atherosclerotic plaque stability. First, we used genomics approaches to identify the molecules that were regulated by CD154. I identified and validated several candidates in atherosclerotic Apoe-/- mice of which TGFβ (Arterioscl. Thromb Vasc Biol 2001), Cathepsin K (Circulation 2006), small inducible cytokines (Circulation 2005), α1β1 (Arterioscl. Thromb Vasc Biol 2001) and hedgehog (J Pathol 2007) all affected atherosclerotic plaque stability. When I started my own independent research group, my research focused on the receptor for CD154, CD40, and I showed that also deficiency of CD40 in Apoe-/- mice was also able to reduce the amount of atherosclerosis, and to induce a stable atherosclerotic plaque phenotype (J Exp Med 2010). Then my group aimed to identify the CD40 and CD154 expressing cell types that were responsible for the induction of the stable plaque phenotype in CD154-/-Apoe-/- and CD40-/-Apoe-/- mice. We found to our great surprise that deficiency of the entire hematopoietic component of CD154 did not affect atherosclerosis (Atherosclerosis 2005). However, injection of activated platelets that were deficient in CD154 prevented the strong progression of atherosclerosis that was observed after injection of CD154+/+ platelets by inhibiting leukocyte recruitment, apoptosis, and the occurrence of intraplaque hemorrhages (Lievens et al, submitted), indicating an important role for platelet CD154 in atherosclerosis.
For CD40, we found deficiency of hematopoietic CD40 mimicked the phenotype we observed in our CD40-/-Apoe-/- mice, suggesting that atherosclerotic plaque stability is induced by CD40 deficiency in one or more of the hematopoietic cell subsets (J Exp Med 2010).
More recently, we therefore focused on the CD40-signal transduction pathways in leukocytes that are responsible for atherosclerosis progression and atherosclerotic plaque stability. CD40 has no intrinsic signaling and signaling is dependent on binding of adaptor molecules, the TNF-receptor associated factors (TRAFs) that elicit downstream signal transduction pathways. Transgenic mouse models were developed in which CD40-/- mice received a CD40 transgene with mutations in the respective TRAF-binding sites. Apoe-/- mice deficient in the CD40-TRAF2/3/5 binding site developed normal levels of atherosclerosis, while mice deficient in CD40-TRAF6 signaling hardly developed any atherosclerotic plaques. These mice also had a decreased number of circulating Ly6Chigh monocytes, which had a hampered capacity to enter the arterial wall. However the effects of deficiency of CD40-TRAF6 signaling on the systemic immune system were limited, making inhibition of CD40-TRAF6 interactions and attractive therapeutic target (J Exp Med 2010).
In sum, my entire research of the past 9 years focused on the investigation of the mechanism how modulation of CD154-CD40 interactions can affect the pathogenesis of atherosclerosis. By using different approaches, my group (consisting of 9 people since 2009) has extensively shown the effects of molecules influenced by the CD154-CD40 system, but also the effects of CD154 and CD40 themselves, their cell-type specific actions, and the signaling pathways they use to affect atherosclerosis, but also the systemic immune system. I’m now at the verge at integrating the knowledge obtained from the CD154-CD40 system to other co-stimulatory pathways, and studying their interactions in atherosclerosis. Moreover, my group is now developing small compounds directed against the CD40 binding pocket of TRAF6, to find a therapeutic target that specifically inhibits CD40-TRAF6 interactions, while leaving all the other CD40-TRAF signaling pathways intact. In this way, we will be able to specifically inhibit atherosclerosis without inducing immune-suppression.

 

PART II: RESEARCH AND TEACHING

A. Funding Information
1. Active Funding
2011-2016 AMC fellowship (PI)
€ 700.000
2011-2015 CARIM PhD grant:
€ 200.000
2007-2012 ZonMW VIDI 016.086.326 (PI).
Revival of CD40(L) as a therapy for atherosclerosis: exploration of downstream pathways as novel therapeutic options.
€ 600.000
2007-2012 ZonMW Aspasia program (PI).
€ 100.000
2008-2013 Sofja Kovalevskaja stipend, Humboldt Stiftung, Germany (PI).
Cell-type specific CD40-signaling in atherosclerosis.
€ 1.650.000
2009-2014 Established Investigator, Dr. E. Dekker Program, Dutch Heart Foundation (PI).
Modulation plaque stabilization through co-stimulation: focus on the immunological synapse.
€ 500.000
2010-2013 Forschergruppe DFG809, teilprojekt 11 (PI).
Function of Co-stimulation in Atherosclerosis.
€ 350.000
2012-2017 PI on CVON-grant (WP 2), GENIUS, Dutch Heart Foundation.
€ 300.000 (€ 5.000.000 consortium grant).

2. Past Funding
2000-2003 Post-doctoral fellowship NWO 902-26-244 (PI).
Macrophage transdifferentiation in atherosclerosis. Focus on the CD40-CD40L system.
€ 200.000
2000-2009 Post-doctoral fellowship Dutch Heart Foundation (2000T041) (PI).
Macrophage and smooth muscle cell differentiation in atherosclerosis. Role of the CD40-CD40L system.
€ 500.000
2001-2002 TALENT-stipend Netherlands Research organization (NWO).
Unraveling of the mechanisms of plaque stabilization using a genomics and proteomics approach
$30.000
2002-2003 Fellowship Dutch Atherosclerosis Society (DAS).
Mechanisms of CD40L inhibition induced plaque stabilization.
€ 3.000
2002-2007 Program Grant Dutch Heart Foundation (NHS 2002B33) (Co-PI).
Functional genomics and imaging to identify new regulators of plaque stabilization
€ 500.000
2003-2006 VENI grant NWO (Netherlands Research Organization, ZonMW) 016.045.085 (PI).
Downstream of the CD40-CD40L dyad in atherosclerosis: the answer for a plaque associated stabilizing therapy?
€ 200.000
2003-2007 Dutch Heart Foundation (NHS) Grant 2003B226 (PI) ‘Downstream of the CD40-CD40L dyad in atherosclerosis: the answer for induction of plaque specific stability?’
€ 227.000.

B. Report of Teaching

General
2000-present Theoretical and practical training of technicians, undergraduate students, PhD-students and post-docs.

PhD- courses
- Lecturer CARIM PhD meeting 2008: How to succeed in research…
- Lecturer CARIM PhD course on physiology 2008/2009: molecular mechanisms of atherosclerosis.
- Lecturer EVGN (European Vascular Genomics Network) summerschool 2007, Sygehur, Sweden: Inflammation in the plaque.
- Organizer and lecturer first EVGN mouse atherosclerosis workshop, 2008, Maastricht, the Netherlands
- Lecturer EuCar program (2008-2012).
- Organizer and lecturer CARIM PhD course on atherosclerosis (2011)

FHML
1998-2002 Practical education in course 4.5 (cur ’88), Medicine, Faculty of Medicine, Maastricht University.
2003/2004 "Tutor" in course 1.3, Medicine, Faculty of Medicine, Maastricht University.
2005/2006 Practical education in course 1.4, Medicine, Faculty of Medicine, Maastricht University.
2006 Lecture: Pathologie van Atherosclerose, course 2.1, Medicine, Faculty of Medicine, Maastricht University.
2006 Lecture: CD40-signaling in Atherosclerosis, CARIM CBM Master’s.
2006 Lecture: Molecular Mechanisms of Plaque Instability, course 3.2, Molecular Life Sciences, TuL.
2007 “Tutor” in course 2.4, Medicine, Faculty of Medicine, Maastricht University.
2007 “Tutor” in course 1.1, Medicine, FHML, Maastricht University.
2007 Lecture: CD40-signaling in atherosclerosis, course 3.2, Molecular Life Sciences, TuL.
2008 “Tutor” in course 2.4, Medicine, Faculty of Medicine, Maastricht University.

2008 Lecture: CD40-signaling in atherosclerosis, course 3.2, Molecular Life Sciences, TuL.
2009 “Tutor” in course 1.4, Medicine, Faculty of Medicine, Maastricht University.
2009 “Tutor” in course 2.4, Medicine, Faculty
2010 “Tutor” in course 1.3, Medicine, Faculty of Medicine, Maastricht University.

2008-2011 Coordinator CBM master program, block 1.2.
2010 Maastricht Medical student conference (MMSRC), scientific advisory board and jury.
2010-2011 CARIM coordinator honours program, FHML.
2012-now Development honours program Medicine, master phase (section scientific development), AMC (UvA)

 

C. Thesis (Co-)Promotorship and Supervision
1. M. Smook
PhD thesis (29/6/2007):
Adaptive immunity in atherosclerosis: an in vivo evaluation.
Co-promotor: Dr. E. Lutgens
Dr. P. Heeringa
Promotor: Prof Dr. M. Daemen
Prof. Dr. J. Cohen-Tervaert

2. D. Lievens
PhD thesis (28/1/2010)
Cell-type specific CD40-CD40L interactions in atherosclerosis.
Promotor: Prof. Dr. M. Daemen; Prof. Dr. E. Biessen
Co-promotor: Dr. E. Lutgens

3. D. Engel
PhD thesis to be delivered March 2012
Promotor: Prof. Dr. E. Lutgens

4. T. Seijkens (MD-PhD program):
PhD thesis to be delivered March 2013
Promotor: Prof. Dr. E. Lutgens
Co-promotor: Dr. M. Tjwa

5. Maryam Sanati (EuCar PhD)
PhD thesis to be delivered February 2012
Promotor: Prof. Dr. E. Lutgens

6. Karin Wildhagen
PhD thesis to be delivered September 2014
Promotor: Prof. Dr. H. ten Cate; Prof. Dr. E. Lutgens
Co-promotor : Dr. G. Nicholaes

7. Wouter Derks
PhD thesis to be delivered January 2015
Promotor: Prof. Dr. S. Heymans, Prof. Dr. E. Lutgens
Co-promotor : Dr. M. van Bilzen

8. Holger Winkels
PhD thesis to be delivered January 2015
Promotor: Prof. Dr. E. Lutgens
Co-promotor : Dr. N. Gerdes

9. Bart Legein
PhD thesis to be delivered September 2015
Promotor: Prof. E. Lutgens, Prof. E. Biessen
Co-promotor : Dr. L. Temmerman

D. Invited lectures

2000
- CD40-CD40L interactions: a key mediator of plaque stability? Pfizer, course for cardiologists, Utrecht, the Netherlands.

2001
- CD40L and TGFβ: balance between fibrosis and inflammation. Pfizer, course for cardiologists, Utrecht, the Netherlands.
- CD40-CD40L, plaque stability and beyond. Pfizer, course for internal medicine, Utrecht, the Netherlands.

2002
- Inhibition of CD40L induces atherosclerotic plaque stability. 4th Houthem symposium Houthem st Gerlach, the Netherlands.
- Inflammation in atherosclerosis, dept of Vascular Medicine, Brigham and Women’s hospital, Harvard Medical School, Boston, MA, USA. Moderator: Prof. P. Libby.

2003
- Determinants of plaque stability: The balance between fibrosis and inflammation. 4th Annual conference on Arteriosclerosis, Thrombosis and Vascular Biology, Washington.

2004
- Molecular mechanisms of plaque stability. 6th Vascular Biology symposium Houthem st Gerlach, Houthem, the Netherlands.
- Determinants of plaque stability: CD40L and beyond. 2nd joint meeting of the Dutch and German molecular cardiology working groups, Vaals, the Netherlands.

2005
- The pathogenesis of plaque rupture. EU-India Thematic Workshop on Genomics and Biotechnology for Health, New Dehli, India.
- CD40-signalling in atherosclerosis. Dept. of Medicine, University College London, London, UK. Moderator: Dr. R. Khurana.
- Atherosclerosis: an inflammatory disease. Dutch Medicine Days 2005, Lunteren, the Netherlands
- Atherosclerosis and CD40L: what lies beneath. 5e Wetenschapsdag Nederlandse Hartstichting, Amsterdam, the Netherlands.

2006
- Immunologic pathways in atherosclerosis: CD40(L) and beyond. International Vascular Biology meeting, IVBM, Noordwijkerhout, the Netherlands.
- Atherosclerotic plaque rupture: immunologic and proteolytic pathways. European Young Physiologist Symposium (EYPS), Munich, Germany.
- Mediators of atherosclerotic plaque stabilisation: immunologic and proteolytic pathways. 4th joint German-Dutch Cardiology Meeting, Utrecht, the Netherlands.
- Mediators of atherosclerotic plaque rupture: immunologic and proteolytic pathways. Amsterdam Medical Center (AMC), University of Amsterdam, the Netherlands. Moderator: Prof. C. de Vries.

2007
- Inhibition of CD40: a potential therapy in atherosclerosis?, Immunology Lecture series, Academic Medical Center Amsterdam, the Netherlands.
- CD40-CD40L signaling in atherosclerosis, KNAW symposium, Amsterdam, the Netherlands.
- Anti-inflammatory strategies in atherosclerosis, keynote lecture, EMVBM (European Medicine and Vascular Biology Meeting), Bristol, UK.
- Inflammation in the plaque, European Vascular Genomics Network (EVGN) Summerschool, Smygehur, Sweden.
- Molecular mechanisms of plaque rupture, Lecture series, Baylor College of Medicine, Houston, Tx, USA. Moderator: Prof X. Wehrens.
- Gefascineerd door moleculen, Dies natalis 2007, Universiteit Maastricht, the Netherlands.

2008
- CD40-CD40L interactions: which TRAFs are crucial? Annual meeting of the German Society for microcirculation and vascular biology (GfMVB), Aachen, Germany.
- CD40-signaling and plaque rupture, European Society of Clinical Investigation (ESCI), Geneva, Switzerland.
- How to succeed in research, CARIM PhD weekend, Kerkrade, the Netherlands.
- Molecular mechanisms of plaque rupture. Vascular Biology Seminar, University of Washington, Seattle, WA, USA. Moderator: Prof. M. Rosenfeld.

2009
- CD40-TRAF6 interactions are crucial in atherosclerosis. Vascular Biology Seminar, Goethe University, Frankfurt, Germany. Moderator: Dr. M. Tjwa.
- Inducing plaque stability by taming the CD40-CD40L system. Seminar dept. of immunology, Dutch Cancer Institute, Amsterdam, the Netherlands. Moderator: Prof. J. Borst.
- Stabilizing the atherosclerotic plaque: taming the CD40-CD40L system. Seminar Institute for Cardiovascular Research (IMCAR), RWTH Aachen, Germany.
Moderator: Prof. C. Weber.
- Genomics of Atherosclerosis: Target validation in mouse models. NAVBO Cardiovascular Genetics and Genomics Meeting, Hyannis, Cape Cod, MA, USA.
- Inducing atherosclerotic plaque stability: taming the CD40- CD40L system. Cardiovascular Grand Rounds, CARIM, Maastricht, the Netherlands. Moderator: Dr. A. Moens.
- Stabilizing the atherosclerotic plaque: taming the CD40-CD40L system. PhD-student club, INSERM 626, Marseille, France. Moderator: Prof. MC Alessi.

2010:
- Targeting cardiovascular disease: manipulating the immune system. Dies natalis, University of Maastricht, Maastricht the Netherlands.
- CD40-TRAF signalling in atherosclerosis, Microvascular Biology Meeting (MIVAB), Biezenmortel, the Netherlands.
- Targeting cardiovascular disease: manipulating the immune system. VU Amsterdam, dept. of Cell Biology, Immunology and Histology, Amsterdam, the Netherlands. Moderator: Prof. A. Horrevoets.
- Molecular Mechanisms of Atherosclerosis: the immune system. Promise Graduate School, Giessen, Germany. Moderator: Prof. K. Preissner.
- Cell type specific CD40(L) signalling. Sofja Kovalevskaja Preistraeger treffen, Cologne, Germany. Moderator: Prof. H. Schwartz.

2011:
- Co-stimulatory molecules in atherosclerosis. Abcam conference: the Leukocyte in Cardiovascular disease, Geneva, Switzerland, Jan 27/28. Organizers: B. Imhof, F. Mach.
- Co-stimulation in cardiovascular disease. U-CARE meeting, UMCU, Utrecht, The Netherlands, Feb 3. Moderator: G. Pasterkamp.
- CD40L-CD40 in atherosclerosis. Gordon Research conference: Mechanisms of atherosclerosis, Providence, RI, USA, June 17-25.
- CD40L-CD40 in atherosclerosis. European Molecular and Vascular Biology Meeting (EmvBM), Krakow, Poland, September 20-24.
- Co-stimulation in vascular disease. Cardiovascular Research and Clinical Implications meeting, Swiss Society of Cardiology, Muntelier, Switzerland, October 6 and 7.
- Atherosclerose en het immuunsysteem. Jubileumdag Landelijk Netwerk Vrouwelijke Hoogleraren, Utrecht, October 6.
- Co-stimulatory molecules in vascular Biology. Friday Seminar, dept of Cardiovascular Medicine, Yale School of Medicine, November 11. Moderator: Prof. M. Simons

E. Meeting Organization
2008-2010 Co-organizer ‘Research Techniques in Immunology’ Lecture series, University of Maastricht, the Netherlands.
2008 Organizer of the 1st EVGN Mouse Atherosclerosis Workshop, April 24-25, Maastricht, the Netherlands.
2011 CARIM PhD course mouse
2012 Session organizer German/Dutch molecular Cardiology Meeting.

PART III: Bibliography
H-Factor: 25, total number of citations: 2942.
1. Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell. 1999;98:147-157 (ipf 31.3).
2. Lutgens E, Daemen M, Kockx M, Doevendans P, Hofker M, Havekes L, Wellens H, de Muinck ED. Atherosclerosis in APOE*3-Leiden transgenic mice: from proliferative to atheromatous stage. Circulation. 1999;99:276-283 (ipf 14.6).
3. Lutgens E, Daemen MJ, de Muinck ED, Debets J, Leenders P, Smits JF. Chronic myocardial infarction in the mouse: cardiac structural and functional changes. Cardiovasc Res. 1999;41:586-593 (ipf 5.9).
4. Lutgens E, de Muinck ED, Kitslaar PJ, Tordoir JH, Wellens HJ, Daemen MJ. Biphasic pattern of cell turnover characterizes the progression from fatty streaks to ruptured human atherosclerotic plaques. Cardiovasc Res. 1999;41:473-479 (ipf 5.9).
5. Lutgens E, Gorelik L, Daemen MJ, de Muinck ED, Grewal IS, Koteliansky VE, Flavell RA. Requirement for CD154 in the progression of atherosclerosis. Nat Med. 1999;5:1313-1316 (ipf 27.6).
6. Kliffen M, Lutgens E, Daemen MJ, de Muinck ED, Mooy CM, de Jong PT. The APO(*)E3-Leiden mouse as an animal model for basal laminar deposit. Br J Ophthalmol. 2000;84:1415-1419 (ipf 2.9).
7. Lutgens E, Cleutjens KB, Heeneman S, Koteliansky VE, Burkly LC, Daemen MJ. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype. Proc Natl Acad Sci U S A. 2000;97:7464-7469 (ipf 9.4).
8. Blankesteijn WM, Creemers E, Lutgens E, Cleutjens JP, Daemen MJ, Smits JF. Dynamics of cardiac wound healing following myocardial infarction: observations in genetically altered mice. Acta Physiol Scand. 2001;173:75-82.
9. Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen MJ. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2001;21:1998-2003 (ipf 6.9).
10. Lutgens E, Daemen MJ. Transforming growth factor-beta: a local or systemic mediator of plaque stability? Circ Res. 2001;89:853-855 (ipf 10.0).
11. Lutgens E, de Muinck ED, Heeneman S, Daemen MJ. Compensatory enlargement and stenosis develop in apoE(-/-) and apoE*3-Leiden transgenic mice. Arterioscler Thromb Vasc Biol. 2001;21:1359-1365 (ipf 6.9).
12. Lutgens E, Daemen MJ. CD40-CD40L interactions in atherosclerosis. Trends Cardiovasc Med. 2002;12:27-32 (ipf 4.1).
13. Lutgens E, Gijbels M, Smook M, Heeringa P, Gotwals P, Koteliansky VE, Daemen MJ. Transforming growth factor-beta mediates balance between inflammation and fibrosis during plaque progression. Arterioscler Thromb Vasc Biol. 2002;22:975-982 (ipf 6.9).
14. Rouwet EV, Tintu AN, Schellings MW, van Bilsen M, Lutgens E, Hofstra L, Slaaf DW, Ramsay G, Le Noble FA. Hypoxia induces aortic hypertrophic growth, left ventricular dysfunction, and sympathetic hyperinnervation of peripheral arteries in the chick embryo. Circulation. 2002;105:2791-2796 (ipf 14.6).
15. Heeneman S, Cleutjens JP, Faber BC, Creemers EE, van Suylen RJ, Lutgens E, Cleutjens KB, Daemen MJ. The dynamic extracellular matrix: intervention strategies during heart failure and atherosclerosis. J Pathol. 2003;200:516-525 (ipf 5.6).
16. Lutgens E, van Suylen RJ, Faber BC, Gijbels MJ, Eurlings PM, Bijnens AP, Cleutjens KB, Heeneman S, Daemen MJ. Atherosclerotic plaque rupture: local or systemic process? Arterioscler Thromb Vasc Biol. 2003;23:2123-2130 (ipf 6.9).
17. Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J. The atherogenic effect of excess methionine intake. Proc Natl Acad Sci U S A. 2003;100:15089-15094 (ipf 9.4).
18. Curfs DM, Lutgens E, Gijbels MJ, Kockx MM, Daemen MJ, van Schooten FJ. Chronic exposure to the carcinogenic compound benzo[a]pyrene induces larger and phenotypically different atherosclerotic plaques in ApoE-knockout mice. Am J Pathol. 2004;164:101-108 (ipf 5.7).
19. Luttun A, Lutgens E, Manderveld A, Maris K, Collen D, Carmeliet P, Moons L. Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth. Circulation. 2004;109:1408-1414 (ipf 14.6).
20. Tkachenko E, Lutgens E, Stan RV, Simons M. Fibroblast growth factor 2 endocytosis in endothelial cells proceed via syndecan-4-dependent activation of Rac1 and a Cdc42-dependent macropinocytic pathway. J Cell Sci. 2004;117:3189-3199 (ipf 6.2).
21. Curfs DM, Knaapen AM, Pachen DM, Gijbels MJ, Lutgens E, Smook ML, Kockx MM, Daemen MJ, van Schooten FJ. Polycyclic aromatic hydrocarbons induce an inflammatory atherosclerotic plaque phenotype irrespective of their DNA binding properties. FASEB J. 2005;19:1290-1292 (ipf 7.0).
22. Leiner T, Gerretsen S, Botnar R, Lutgens E, Cappendijk V, Kooi E, van Engelshoven J. Magnetic resonance imaging of atherosclerosis. Eur Radiol. 2005;15:1087-1099 (ipf 2.3).
23. Lutgens E, Faber B, Schapira K, Evelo CT, van Haaften R, Heeneman S, Cleutjens KB, Bijnens AP, Beckers L, Porter JG, Mackay CR, Rennert P, Bailly V, Jarpe M, Dolinski B, Koteliansky V, de Fougerolles T, Daemen MJ. Gene profiling in atherosclerosis reveals a key role for small inducible cytokines: validation using a novel monocyte chemoattractant protein monoclonal antibody. Circulation. 2005;111:3443-3452 (ipf 14.6).
24. Schapira K, Lutgens E, de Fougerolles A, Sprague A, Roemen A, Gardner H, Koteliansky V, Daemen M, Heeneman S. Genetic deletion or antibody blockade of alpha1beta1 integrin induces a stable plaque phenotype in ApoE-/- mice. Arterioscler Thromb Vasc Biol. 2005;25:1917-1924 (ipf 6.9).
25. Smook ML, Heeringa P, Damoiseaux JG, Daemen MJ, de Winther MP, Gijbels MJ, Beckers L, Lutgens E, Tervaert JW. Leukocyte CD40L deficiency affects the CD25(+) CD4 T cell population but does not affect atherosclerosis. Atherosclerosis. 2005;183:275-282 (ipf 4.6).
26. Bijnens AP, Lutgens E, Ayoubi T, Kuiper J, Horrevoets AJ, Daemen MJ. Genome-wide expression studies of atherosclerosis: critical issues in methodology, analysis, interpretation of transcriptomics data. Arterioscler Thromb Vasc Biol. 2006;26:1226-1235 (ipf 6.9).
27. Lobbes MB, Lutgens E, Heeneman S, Cleutjens KB, Kooi ME, van Engelshoven JM, Daemen MJ, Nelemans PJ. Is there more than C-reactive protein and fibrinogen? The prognostic value of soluble CD40 ligand, interleukin-6 and oxidized low-density lipoprotein with respect to coronary and cerebral vascular disease. Atherosclerosis. 2006;187:18-25 (ipf 4.6).
28. Lutgens E, Lutgens SP, Faber BC, Heeneman S, Gijbels MM, de Winther MP, Frederik P, van der Made I, Daugherty A, Sijbers AM, Fisher A, Long CJ, Saftig P, Black D, Daemen MJ, Cleutjens KB. Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation. 2006;113:98-107 (ipf 14.6).
29. Lutgens SP, Kisters N, Lutgens E, van Haaften RI, Evelo CT, de Winther MP, Saftig P, Daemen MJ, Heeneman S, Cleutjens KB. Gene profiling of cathepsin K deficiency in atherogenesis: profibrotic but lipogenic. J Pathol. 2006;210:334-343 (ipf 5.6).
30. Mulder WJ, Douma K, Koning GA, van Zandvoort MA, Lutgens E, Daemen MJ, Nicolay K, Strijkers GJ. Liposome-enhanced MRI of neointimal lesions in the ApoE-KO mouse. Magn Reson Med. 2006;55:1170-1174 (ipf 3.4).
31. Beckers L, Heeneman S, Wang L, Burkly LC, Rousch MM, Davidson NO, Gijbels MJ, de Winther MP, Daemen MJ, Lutgens E. Disruption of hedgehog signalling in ApoE - /- mice reduces plasma lipid levels, but increases atherosclerosis due to enhanced lipid uptake by macrophages. J Pathol. 2007;212:420-428 (ipf 5.6).
32. Lutgens E, Lievens D, Beckers L, Donners M, Daemen M. CD40 and its ligand in atherosclerosis. Trends Cardiovasc Med. 2007;17:118-123 (ipf 4.2).
33. Donners MM, Beckers L, Lievens D, Munnix I, Heemskerk J, Janssen BJ, Wijnands E, Cleutjens J, Zernecke A, Weber C, Ahonen CL, Benbow U, Newby AC, Noelle RJ, Daemen MJ, Lutgens E. The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling. Blood. 2008;111:4596-4604 (ipf 10.4).
34. Heeneman S, Lutgens E, Schapira KB, Daemen MJ, Biessen EA. Control of atherosclerotic plaque vulnerability: insights from transgenic mice. Front Biosci. 2008;13:6289-6313 (ipf 3.3).
35. Leroyer AS, Rautou PE, Silvestre JS, Castier Y, Leseche G, Devue C, Duriez M, Brandes RP, Lutgens E, Tedgui A, Boulanger CM. CD40 ligand+ microparticles from human atherosclerotic plaques stimulate endothelial proliferation and angiogenesis a potential mechanism for intraplaque neovascularization. J Am Coll Cardiol. 2008;52:1302-1311 (ipf 11.4).
36. Lutgens E, Tjwa M, Garcia de Frutos P, Wijnands E, Beckers L, Dahlback B, Daemen MJ, Carmeliet P, Moons L. Genetic loss of Gas6 induces plaque stability in experimental atherosclerosis. J Pathol. 2008;216:55-63 (ipf 5.6).
37. Smook ML, van Leeuwen M, Heeringa P, Damoiseaux JG, Theunissen R, Daemen MJ, Lutgens E, Cohen Tervaert JW. Anti-oxLDL antibody isotype levels, as potential markers for progressive atherosclerosis in APOE and APOECD40L mice. Clin Exp Immunol. 2008;154:264-269 (ipf 2.9).
38. Tjwa M, Bellido-Martin L, Lin Y, Lutgens E, Plaisance S, Bono F, Delesque-Touchard N, Herve C, Moura R, Billiau AD, Aparicio C, Levi M, Daemen M, Dewerchin M, Lupu F, Arnout J, Herbert JM, Waer M, Garcia de Frutos P, Dahlback B, Carmeliet P, Hoylaerts MF, Moons L. Gas6 promotes inflammation by enhancing interactions between endothelial cells, platelets, and leukocytes. Blood. 2008;111:4096-4105 (ipf 10.4).
39. Engel D, Seijkens T, Poggi M, Sanati M, Thevissen L, Beckers L, Wijnands E, Lievens D, Lutgens E. The immunobiology of CD154-CD40-TRAF interactions in atherosclerosis. Semin Immunol. 2009;21:308-312 (ipf 9.1).
40. Kuijpers MJ, Gilio K, Reitsma S, Nergiz-Unal R, Prinzen L, Heeneman S, Lutgens E, van Zandvoort MA, Nieswandt B, Egbrink MG, Heemskerk JW. Complementary roles of platelets and coagulation in thrombus formation on plaques acutely ruptured by targeted ultrasound treatment: a novel intravital model. J Thromb Haemost. 2009;7:152-161 (ipf 6.3).
41. Lievens D, Eijgelaar WJ, Biessen EA, Daemen MJ, Lutgens E. The multi-functionality of CD40L and its receptor CD40 in atherosclerosis. Thromb Haemost. 2009;102:206-214 (ipf 3.8).
42. Tjwa M, Moons L, Lutgens E. Pleiotropic role of growth arrest-specific gene 6 in atherosclerosis. Curr Opin Lipidol. 2009;20:386-392 (ipf 6.6).
43. Xanthoulea S, Thelen M, Pottgens C, Gijbels MJ, Lutgens E, de Winther MP. Absence of p55 TNF receptor reduces atherosclerosis, but has no major effect on angiotensin II induced aneurysms in LDL receptor deficient mice. PLoS One. 2009;4:e6113.
44. Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Koppel T, Jahantigh MN, Lutgens E, Wang S, Olson EN, Schober A, Weber C. Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal. 2009;2:ra81.
45. Zouggari Y, Ait-Oufella H, Waeckel L, Vilar J, Loinard C, Cochain C, Recalde A, Duriez M, Levy BI, Lutgens E, Mallat Z, Silvestre JS. Regulatory T cells modulate postischemic neovascularization. Circulation. 2009;120:1415-1425 (ipf 14.6).
46. Bai L, Beckers L, Wijnands E, Lutgens SP, Herias MV, Saftig P, Daemen MJ, Cleutjens K, Lutgens E, Biessen EA, Heeneman S. Cathepsin K gene disruption does not affect murine aneurysm formation. Atherosclerosis 2010;209:96-103 (ipf 4.6).
47. Hristov M, Gumbel D, Lutgens E, Zernecke A, Weber C. Soluble CD40 ligand impairs the function of peripheral blood angiogenic outgrowth cells and increases neointimal formation after arterial injury. Circulation 2010;121:315-324 (ipf 14.6).
48. Loges S, Schmidt T, Tjwa M, van Geyte K, Lievens D, Lutgens E, Vanhoutte D, Borgel D, Plaisance S, Hoylaerts M, Luttun A, Dewerchin M, Jonckx B, Carmeliet P. Malignant cells fuel tumor growth by educating infiltrating leukocytes to produce the mitogen Gas6. Blood 2010;115:2264-2273 (ipf 10.4).
49. Lutgens E, Lievens D, Beckers L, Wijnands E, Soehnlein O, Zernecke A, Seijkens T, Engel D, Cleutjens J, Keller AM, Naik SH, Boon L, Oufella HA, Mallat Z, Ahonen CL, Noelle RJ, de Winther MP, Daemen MJ, Biessen EA, Weber C. Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile. J Exp Med 2010;207:391-404 (ipf 15.5).
50. Lutgens E, Poggi M, Weber C. CD40L-CD40 fuel ignites obesity. Thromb Haemost 2010;103:694-695 (ipf 3.8).
51. Goossens P, Gijbels MJJ, Zernecke A, Eijgelaar W, Vergouwe MN, van der Made I, Vanderlocht J, Beckers L, Buurman WA, Daemen MJAP, Kalinke U, Weber C, Lutgens E, de Winther MPJ. Myeloid type I interferon signaling promotes atherosclerosis by stimulating macrophage recruitment to lesions. Cell Metabol 2010, 104: 142-153 (ipf 16.1).
52. Seijkens T, Engel D, Tjwa M, Lutgens E. The role of CD154 in haematopoietic development. Thromb Haemost 2010; 104: 693-701.
53. Lievens D, Zernecke A, Seijkens T, Soehnlein O, Beckers L, Munnix IC, Wijnands E, Goossens P, van Kruchten R, Thevissen L, Boon L, Flavell RA, Noelle RJ, GerdesN, Biessen EA, Daemen MJ, Heemskerk JW, Weber C, Lutgens E. Platelet CD40L mediated thrombotic and inflammatory processes in atherosclerosis. Blood 2010; 116:4317-27.
54. Meuwese MC, Broekhuizen LN, Kuikhoven M, Heeneman S, Lutgens E, Gijbels MJ, Nieuwdorp M, Peutz CJ, Stroes ES, Vink H, van den Berg BM. Endothelial surface layer degradation by chronic hyaluronidase infusion induces proteinuria in apolipoprotein E-deficient mice.PLoS One; 2010:e14262.
55. Lobbes MB, Kooi ME, Lutgens E, Ruiters AW, Lima Passos V, Braat SH, Rousch M, Ten Cate H, van Engelshoven JM, Daemen MJ, Heeneman S. Leukocyte counts, myeloperoxidase, and pregnancy-associated plasma protein a as biomarkers for cardiovascular disease: towards a multi-biomarker approach. Int J Vasc Med 2010;2010:726207.
56. Engel D, Beckers L, Wijnands E, Seijkens T, Lievens D, Drechsler M, Gerdes N, Soehnlein O, Daemen MJ, Stan RV, Biessen EA, Lutgens E. Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response. FASEB J 2011;25: 3838-3848.
57. Poggi M, Engel D, Christ A, Beckers L, Wijnands E, Boon L, Driessen A, Cleutjens J, Weber C, Gerdes N, Lutgens E. CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice. Arterioscl Thromb Vasc Biol 2011;31:2251-60.
58. Lutgens E, Binder CJ. Immunology of atherosclerosis. Thromb Haemost 2011 106: 755-756.
59. Daissormont IT, Christ A, Temmerman L, Sampedro Millares S, Seijkens T, Manca M, Rousch M, Poggi M, Boon L, van der Loos C, Daemen M, Lutgens E, Halvorsen B, Aukrust P, Janssen E, Biessen EA. Plasmacytoid dendritic cells protect against atherosclerosis by tuning T-cell proliferation and activity. Circ Res 2011. 109: 1387-95.
60. Wildhagen KC, Lutgens E, Loubele ST, Ten Cate H, Nicolaes GA. The structure-function relationship of activated protein C. Lessons from natural and engineered mutations. Thromb Haemost 2011 106:1034-45.
61. Lutgens E, Leiner T, Weber C. RANK(L)-ing biomarkers as surrogates for coronary calcium score. Thromb Haemost 2012, in press.
62. Papageorgiou A, Swinnen M, Vanhoutte D, Vandendriessche T, Chuah M, Lindner D, Verhesen W, de Vries B, D'Hooge J, Lutgens E, Westermann D, Carmeliet P, Heymans S. Thrombospondin-2 prevents cardiac injiry and dysfunction in viral myocarditit through the activation of regulatory T-cells. Cardiovasc Res 2012, in press

Submitted publications
1. Beckers L, Lievens D, Wijnands E, Benbow U, Flavell R, Daugherty A, Newby A, Daemen M, Lutgens E. CD40L deficiency protects against aneurysm formation: a novel prevention strategy?
2. Lievens D, Habets K, Robertson A, Beckers L, Laouar Y, Wijnands E, Rudling M, Flavell R, Daemen M, Kuijper J, Biessen E, Lutgens E. Deficiency of TGFβ signaling in CD11c+ cells accelerates atherosclerosis by inducing inflammatory T-cell influx.

Bookchapters
1. Lutgens E, Leiner T, Daemen M. Molecular basics of vulnerable plaques.In: The vulnerable plaque, J. Schaar et al, 2007.
2. Bai L, Lutgens E, Heeneman S. Cathepsins in Atherosclerosis. In: Molecular and Cellular Mechanisms Underlying Atherosclerosis, George S and Johnson J, 2010.
3. Gerdes N, Lutgens E. Co-stimulation in atherosclerosis, Weber and Sohnlein, 2012.

 

Prof. PhD E. Lutgens (Immune checkpoint regulators in cardiovascular disease)

Postdocs
PhD D. Atzler
PhD E. Kluza
PhD A.G. Shami
PhD C.M. van Tiel

PhD Students
MSc T.J. Beldman
C. Bürger

Others
MSc L. Beckers
S.M. den Toom

• L.A. Bosmans
• M.F. Jansen
• H.H. Poelman
• K. Poels
• M.E. Reiche
• M.M.T. van Leent
• B.W. van Os
• W.G. Vos
• L. Willemsen

• AMC
• AMC (Vrijgesteld)
• Europese Unie
• NWO
• Nederlandse Hartstichting