Curriculum vitae and Bibliography. Univ.-Prof. Dr. med. Christian Weber

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1 Curriculum vitae - Prof. Dr. Christian Weber 1 Curriculum vitae and Bibliography Univ.-Prof. Dr. med. Christian Weber Page Biographical Data and Professional Development 2 Short-Listings, Honours, Memberships and Academic Duties 3 Reviewer, Consultant and Patents 4 Research Grants and External Funding 6 Clinical Training and Teaching Activities 8 Supervision of PhD students and postdoctoral fellows 9 Research Areas and Interests 10 Bibliography most important Original Articles and Bibliometric Data 13 Original Articles 14 Review Articles 29 Invited Lectures and Key Note Lectures (Selection) 35

2 Curriculum vitae - Prof. Dr. Christian Weber 2 Curriculum vitae Christian Weber, MD Univ.-Prof. Dr. med., Chair in Vascular Medicine Director, Institute for Cardiovascular Prevention (IPEK) Hospital of the University of Munich Ludwig-Maximilians-University Munich Pettenkoferstraße 9, München, Germany born October 15, 1967 in Munich, Germany 1986, June Graduation from Gymnasium, Munich (Abitur: 1.0, top 0.1%) Scholarship by the Bavarian State Secretary of Culture Studies in Medicine at Ludwig-Maximilians-University (LMU) Munich, University Hospital Galway, Ireland, Princess Alexandra Hospital, Australia Graduate student at the Institute for Prevention of Cardiovascular Disease, LMU Munich, Scholarship by the August-Lenz-Foundation 1993, June Clinical examination and Graduation from Medical School, ECFMG passed Intern and Resident in Internal Medicine, LMU Munich 1994, March M.D. from LMU Munich with merits ( summa cum laude ) Postdoctoral Research Fellow at Center for Blood Research (T. Springer) Harvard Medical School, funding: Deutsche Forschungsgemeinschaft (DFG) Resident and Assistant Professor (C1) in Cardiovascular Medicine at LMU Award and Head of DFG Junior Research Group in Biosciences Resident and Assistant Professor (C1) in Internal Medicine/Vascular Medicine 2000, January Facultas Docendi & Venia Legendi (Senior Lecturer in Experimental Medicine) 2001, June Appointment to Full Professor (C3) and Head of Molecular Cardiology at University Hospital of the RWTH Aachen University 2002, January Head of Cardiovascular Research and Board Member, Interdisciplinary Center for Clinical Research at the RWTH Aachen University Cardiology Fellowship, focus on coronary artery disease 2003, June Board Certification and Attending Fellow in Internal Medicine 2003, September Organizer 1 st Euregio-Symposium on Atherosclerosis Molecular Basis of an Inflammatory Disease under the auspices of European Society of Cardiology 2004, September Board Certification in Cardiology, Fellow of the European Society of Cardiology 2004, September Offer for Cardiovascular Division Chief, University of Virginia 2005, May Offer for Chair in Cardiology, St. Thomas Hospital, King s College, London 2005, November Appointment to Chair (W3) in Molecular Cardiology and Director of the Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen 2006, October - Joint appointment as Adjunct Professor at CARIM, University of Maastricht 2007, January Spokesman of the DFG program project grant FOR , August Offer for Chair in Molecular Cardiology, Heinrich-Heine-University, Düsseldorf 2008, September Organizer and President, Society of Microcirculation & Vascular Biology 2008, June - Spokesman of the EuCAR Graduate School GRK 1508 in cooperation with 2010, October the University of Maastricht (European Cardiovascular Research School) 2010, November Appointment to Chair (W3) in Preventitive Vascular Medicine and Director of the Institute for Cardiovascular Prevention, LMU Munich 2011, Januara

3 Curriculum vitae - Prof. Dr. Christian Weber 3 Short-listed: 2000 C3 Medical Molecular Biology, University of Erlangen (secundo loco) 2001 C3 Cardiovascular Molecular Biology, RWTH Aachen University (primo loco) 2004 Chair in Cardiology, University of Virginia (primo loco, offer) 2005 Recruitment Symposium W3 Vascular Development Max-Planck-Institut für Molekulare Biomedizin, Münster (shortlisted) 2005 Recruitment Symposium W3 Development & Remodelling of the Vascular System, Max-Planck-Institut für Herz- & Lungenforschung, Bad Nauheim 2005 Chair in Cardiology, King s College London (primo loco, offer) 2007 W3 Mol. Cardiology, Heinrich-Heine-University Düsseldorf (secundo loco, offer) 2009 Professor for Medicinal Chemistry, ETH Zürich (shortlisted) 2009 W3 Preventative Vascular Medicine, LMU München (primo loco, offer) 2010 W3 Mol. Arteriosclerosis Research, Director Leibniz-Institute (primo loco, offer) Honours: Member: - Young Master Award 2000, German Society of Internal Medicine - German Society of Microcirculation and Vascular Biology Award Basic Medical Research Award 2003, GlaxoSmithKline Foundation - Arthur-Weber-Award 2004, German Cardiac Society - Hans & Gertie Fischer Prize 2004, Rhine-Westfalia Society of Internal Medicine - Forßmann Prize 2005, Ruhr-University Bochum - Hermann-Rein-Award 2005, Society for Microcirculation and Vascular Biology - University Patent Award North-Rhine Westfalia H.W. Hauss-Award of the German Society for Atherosclerosis Research Paul-Martini-Award Outstanding Achievment Award 2008, European Society of Cardiology (ESC) - Prix Galien Germany ATVB Special Recognition Award 2009, American Heart Association - ERC Advanced Investigator Grant American Heart Association (AHA) - Centre for Advanced Studies, Ludwig-Maximilians-University Munich - German Cardiac Society (DGK) o Working group Vascular Biology o Vice Chair, Committee for Experimental Cardiology German Centre for Cardiovascular Research (GCCR), Munich Heart Alliance - German Society for Atherosclerose (DGAF) - German Society for Microcirculation and Vascular Biology o President and Strategic Advisor German Society for Immunology, Working Group Adhesion Molecules - German Society for Angiology - European Atherosclerosis Society (EAS) o Scientific Committee Member European Vascular Biology Organisation (EVBO Founding Member) - European Vascular Genomic Network (EVGN Associate Member) - European Society of Cardiology o Fellow and Chair, Working Group of Atherosclerosis and Vascular Biology - European Society for Microcirculation - International Society of Thrombosis and Haemostasis (Scientific Advisory Board) - International Vascular Biology Meeting IVBM 2010 (Scientific Advisory Board) - International Vascular Biology Meeting IVBM 2012 (Co-Organizer/President) - Abcam Meeting on Inflammation and Atherosclerosis 2012 (Organizer)

4 Curriculum vitae - Prof. Dr. Christian Weber 4 Editor-in-Chief Thrombosis and Haemostasis (2010- ) Senior Associate Arteriosclerosis, Thrombosis and Vascular Biology (07/2012- ) Editor Editorial - Basic Research in Cardiology Boards: - Cardiovascular Research - Circulation Research (Superior Editorial Consultant, Guest Editor) - Drug Discovery Today (Section Editor) - EMBO Molecular Medicine - European Heart Journal - Molecular Medicine Reports Reviewer: - American Journal of Physiology - Annals of Internal Medicine - Atherosclerosis - Blood - Cardiovascular Research - Circulation - Diabetes, Obesity & Metabolism - EMBO Journal - FASEB Journal - FEBS Letters - Immunity - Journal of Biological Chemistry - Journal of Cell Biology - Journal of Clinical Investigation - Journal of Experimental Medicine - Journal of Immunology - Journal of Molecular and Cellular Cardiology - Journal of Cellular and Molecular Medicine - Journal of Molecular Medicine - Journal of Pathology - Journal of the American College of Cardiology - Journal of Thrombosis & Haemostasis - Lancet - Nature - Nature Medicine - Proceeding of the National Acadamy of Sciencs of the USA - Science - Science Signaling - Stroke - Trends in Immunology - - Deutsche Forschungsgemeinschaft u.a. SFB 293, 451, 553, 688, 731, 753, 788, 834 GRK 865, 880, Schweizerischer Nationalfonds - MPG Minerva Foundation - - Science Foundation Ireland - Israel Science Foundation - The Wellcome Trust - British Heart Foundation Consultant: - ProtAffin AG - Carolus Therapeutics Inc. (Chair Scientific Advisory Board)

5 Curriculum vitae - Prof. Dr. Christian Weber 5 Patents: - DE (RANTES antagonists for the treatment of restenosis) - US 60/371,734 (JAM-1 small molecule antagonists and antibodies) - DE (customized parallel wall flow chamber) - DE/US UD40009/SAM (peptide antagonist CKEY2) - WO 2007/ A1 (peptide antagonist CKEY2) - US 60/995,185 & 60/923,077 (Methods for regulating CXCR6) - US 65/701,601 (MIF receptor antagonists) - WO 2009/ A1 (GAG-antagonising MCP-1 mutants) - WO 2009/ (mir-126 and tissue repair) - EP (CCL17 inhibitors in T helper cell-driven disease) - EP (Inhibitors of CD40-TRAF6 interaction) Founder: Academic Administration: Carolus Therapeutics Inc. (co-owner) - Member Research Committee of the Medical Faculty - Spokesman PhD-Committee - Member and Spokesman of multiple Recruitment Committees - Co-cordinator of the Munich Heart Alliance (MHA) at the German Centre for Cardiovascular Research (GCCR)

6 Curriculum vitae - Prof. Dr. Christian Weber 6 Research Grants and External Funding Deutsche Forschungsgemeinschaft Research scholarship WE 1913/1-1 Integrin activation by chemokines approx Junior Research Group in Biomedical Research WE 1913/2-1 Integrins and chemokine receptors: regulatory mechanisms and pathophysiological role approx Extension WE 1913/2-2 Integrin and chemokine signalling in inflammatory leukocyte recruitment approx GRK 438 (graduate college grant) A1 Endothelial chemokine receptors and apoptosis approx Single group grant WE 1913/2-3 Integrin ligands and chemokine function in atherogenic leukocyte recruitment approx Single group grant WE 1913/5-1+2 Functional role and mechanisms of platelet chemokines in atherosclerosis and restenosis approx Single group grant BE 1977/2-1 MIF-mediated inflammatory processes in atherogenesis (cooperation with Dr. Bernhagen) approx Single group grant WE 1913/7-1+2 SDF-1α and vascular progenitor cells approx SFB542 (program project grant) C12 YB-1 and functional RANTES expression approx Single Group grant WE 1913/9-1+2 JAM-A in inflammation and atherosclerosis approx FACS Sorter (HBFG) 148/711-1 approx photon-microscopy (HBFG) 222/778-1 approx Program grant FOR809 (Spokesman: C. Weber) TP1 Chemokines and Adhesion Molecules in Cardio- TP2 vascular Pathogenesis: Role of MIF (TP1) TP3 platelet chemokines (TP2), dendritic cells (TP3), TP4 progenitors (TP4) and junctional molecules (TP6) TP6 approx Single Group grant WE 1913/13-1 ADAM shedding in inflammation & atherosclerosis approx SFB542 MIF receptor complexes (with Dr. Bernhagen) A7 approx Shedding by ADAMs (with Dr. Ludwig) A12 approx YB-1 and RANTES expression (with Dr. Mertens) C12 approx SFB TRR57 MIF & CXCR2 in liver fibrosis (with Dr. Wasmuth) PO7 approx GRK 1508 Euregio Cardiovascular Research School approx GRK 1035 Biointerface (with Drs. Zernecke/Klee) approx

7 Curriculum vitae - Prof. Dr. Christian Weber 7 Excellence initiative (DFG 3. funding line) Growth Area Molecular Science and Engineering (MSE6) approx Project House Cell Adhesion at Vascular Interfaces (MT07) approx Program Grant FOR809 (Sprecher: C. Weber) TP1 Chemokines and Adhesion Molecules in Cardio- TP2 vascular Pathogenesis: Role of MIF (TP1) TP3 platelet chemokines (TP2), dendritic cells (TP3), TP4 progenitors (TP4), junctional molecules (TP6), TP6 molecular imaging (TP12), WE 1913/ TP12 approx Centre Grant SFB914 Differential recruitment of monocyte subsets B08 approx (with PD Dr. Söhnlein) Centre Grant SFB1054 Differential recruitment of monocyte subsets B04 approx FACS-sorter system (lead applicant) INST408/97-1 approx photon-microscope (lead applicant) INST408/98-1 approx LMUexcellent for STED microscopy approx Bundesministerium für Bildung und Forschung (BMBF) Munich Heart Alliance (Ko-Koordinator) im DZHK 7.2 Mio. (C. Weber) approx IntenC Research Grant TUR 10/I13: Lipotoxic Stress approx (with Dr. E. Erbay) META JTC 2011: mir-a (with Prof. Schober) approx. 1.0 Mio Metabolic Syndrome and Atherosclerosis: Role of micrornas (C. Weber) approx Industry funding and Foundations approx International ERC Advanced Investigator Grant Atheroprotect 2.5 Mio NWO VICI Grant ( ) 1.5 Mio Leducq Transatlantic Network of Excellence (coordinator) 5.0 Mio. (C. Weber) approx Total third party funding ( ) > 27.0 Mio. DFG funding > 14.0 Mio.

8 Curriculum vitae - Prof. Dr. Christian Weber 8 Clinical Training and Experience (since 1993) - Board Certified Physician and Cardiologist, especially Coronary Artery Disease and Prevention - Long-standing experience in diagnostic catheterization including valves, right heart and bypasse - Substantial experience in coronary intervetion, percutaneous angioplasty and stent placement - Substantial experience in outpatient angiology, hypertension/nephrology and metabolism - Substantial experience in transthoracic & transesophageal echocardiography, duplex- and Doppler-ultrasound of the cranial, renal and peripheral arteries, and segment oscillography - Consultant in a cardiovascular prevention ambulance Teaching Activities (since 2001) Graduate and undergraduate seminars and lectures at LMU Munich and RWTH Aachen: - Biochemical basis and pathophysiology of atherosclerosis - Pathobiochemistry of cellular signal transduction - Experimental methods of cardiovascular research - Epidemiology and clinical prevention of cardiovascular disease - Graduate course: Vascular biology in Medicine - Practical course in Internal Medicine - Molecular mechanisms of inflammatory disease - Lecture round in Molecular Medicine - Lecture round in Internal Medicine and Pathophysiology - Lecture round in Molecular Pathology (for scientists) - Molecular mechanisms of atherogenesis and restenosis - Immunology and signal transduction in inflammatory disease - Molecular imaging and stem cell biology in cardiovascular medicine - Lectures and Master Classes in Vascular Biology and Medicine - Introduction to independent scientific work and thesis - Participation in the cardiovascular system block of the model curriculum - Participation in the qualification profile human genetics and cell biology - Participation in the Methods seminar and Molecular Medicine in the PhD program - Participation in Molecular Imaging module in Biomedical Engineering The full scope of teaching should follow the premise and pursuit of striving for scientific and professional excellence and comply with the conscienceness of humanitarian and human obligation. A teaching contract between the student and the lecturer should define and fulfill the expectations and requirements in individualized form and should form the basis for effective teaching. Systemrelated teaching contents can be structured in lectures, intensified in small group seminars and illustrated and exemplified in computer-based model and case studies. The introduction to scientific and evidence-based gold standards and their application does not only serve an encyclopaedic education, but beyond should promote the personal development along the ideals of the universitas.

9 Curriculum vitae - Prof. Dr. Christian Weber 9 Supervision of PhD students, postdoctoral and junior research fellows PhD students: - Dr. rer. hum. biol. Wolfgang Erl ( summa cum laude, 1996, LMU München) - Dr. rer. nat. Georg Ostermann ( summa cum laude, 2002, LMU München) - Dr. rer. nat. Line Fraemohs ( summa cum laude, 2007, RWTH Aachen) - Dr. rer. medic. Elisa Liehn, M.Sc. ( summa cum laude, 2008, RWTH Aachen) - Dr. rer. nat. Regina Krohn ( summa cum laude, 2008, RWTH Aachen) - Dr. rer. nat. Svenja Meiler ( summa cum laude, 2010, RWTH Aachen) - Dr. rer. nat. Yvonne Döring ( summa cum laude, 2011, RWTH Aachen) - Dr. rer. nat. Alisina Sarabi ( magna cum laude, 2010, RWTH Aachen) - Dr. rer. nat. Maik Drechsler ( magna cum laude, 2011, RWTH Aachen) - Dr. rer. nat. Sakine Simsekyilmaz ( magna cum laude, 2012, RWTH Aachen) - Dr. rer. nat. Sarawuth Wantha ( magna cum laude, 2013, RWTH Aachen) - Elena Vasina, PhD (2013, Maastricht University) o Dipl.-Biol. Martin Schmitt o Dipl.-Biol. Patricia Tilstam MD students: - Dr. med. Celina Wardemann ( magna cum laude, 1998, LMU München) - Dr. med. Philipp von Hundelshausen ( summa cum laude, 2003, LMU München) - Dr. med. Tobias Weber ( summa cum laude, 2004, LMU München) - Dr. med. Alma Zernecke ( summa cum laude, 2004, LMU München) - Dr. med. Britta Butzbach ( magna cum laude, 2006, RWTH Aachen) - Dr. med. Ute Zeiffer ( summa cum laude, 2008 RWTH Aachen) - Dr. med. Dipl.-Chem. Thomas Baltus ( summa cum laude, 2008 RWTH Aachen) - Dr. med. Yassin Djalali-Talab ( summa cum laude, 2009, RWTH Aachen) - Dr. med. Denis Gümbel ( summa cum laude, 2010, RWTH Aachen) - Dr. med. Sebastian Mause ( summa cum laude, 2011, RWTH Aachen) o cand.med. Veit Eckart Post-docs/junior scientists: - Dr. med. Chimge Günther - Dr. med. Thomas Abahji - Dr. med. Felix Vogt - Dr. med. Christian Fach - Dr. med. Alexander Schuh - Dr. med. Stefanie Keymel - Dr. med. Mihail Hristov - Dr. med. Andreas Götzenich - Dr. rer. nat. Kiril Bidzhekov - Dr. rer. nat. Otilia Postea - Dr. rer. nat. Sandra Cauwenberghs - Dr. med. Oliver Söhnlein, PhD - Dr. med. Xuefang Ren - Dr. med. Zuzanna Rowinska - Dr. rer. nat. Heidi Noels - Dr. rer. nat. Xavier Blanchet - Dr. rer. nat. Marcella Langer Habilitations: - PD Dr. med. Andreas Schober - PD Dr. med. Alma Zernecke - PD Dr. ing. Rory Koenen - PD Dr. med. Oliver Söhnlein, PhD - PD Dr. med. Mihail Hristov - PD Dr. med. Elisa Liehn

10 Curriculum vitae - Prof. Dr. Christian Weber 10 Research areas and interests Chemokines in atherosclerosis, vascular inflammation and remodelling An impressive body of work has established the paradigm of atherosclerosis as an inflammatory process promoting lesion development and progression. Early atheroma formation is characterized by leukocyte recruitment and expression of inflammatory mediators which is confounded in the context of hyperlipidemia. Evidence for an involvement of both innate and adaptive immunity in lesion formation has emerged, supporting a causal relation between the balance of pro- and anti-inflammatory cytokines and atherogenesis. The function of chemokines in distinct steps and during recruitment of different mononuclear cell subsets to vascular lesions has been studied in genetically deficient mice, and displays a high degree of specialization and cooperation. The contribution of platelet chemokines deposited on endothelium to monocyte arrest, differences in the presentation and involvement of chemokines between native and neointimal lesion formation, and related functions of macrophage migration inhibitory factor, a cytokine with striking structural homology to chemokines are of note. New roles of chemokines in the recruitment of vascular progenitors and monocyte subsets, and in the control of neutrophil homeostasis during primary atherosclerosis, neointimal hyperplasia and in the recovery of endothelial denudation underscore their relevance for atherosclerotic vascular disease. The functional diversity of chemokines and mononuclear cell subsets in vascular inflammation may allow a selective therapeutic targeting of different atherosclerotic conditions. Our current efforts focus on several specific areas extending these leads. Platelets, chemokines and chemokine receptors in atherosclerosis The mechanisms underlying the intricate functional interplay of platelets and chemokines as culprits in the pathogenesis of vascular disease will be investigated. In particular, specialization of platelet chemokines for monocyte arrest on activated or atherosclerotic endothelium and for endothelial migration and angiogenesis will be explored in correlation to their immobilization to proteoglycans, oligomerization and cleavage by proteases. The cellular and molecular mechanisms of chemokine deposition by platelets (e.g. signaling and microparticles) will be further defined. Heterophilic interactions of PF4 and its non-allelic variant with RANTES and their functional consequences will be characterized in detail using surface plasmon resonance with synthetic and recombinant proteins, in vitro recruitment and migration assays, and using transgenic mice generated for knocking these chemokines or mutant variants out or in. Moreover, we will use NMR circular dichroism spectroscopy or isothermal fluorescence titration for analyzing peptides designed to disrupt such chemokine heteromers and to allow studies confirming their relevance using models of atherosclerosis in vivo. To further investigate the impact of different chemokines and their receptors on the formation of atherosclerotic and neointimal plaques, lesional cell and cytokine content and the recruitment of vascular cells (e.g. macrophages, smooth muscle cell progenitors, T and dendritic cells), mice deficient in CCL17, CCR1, 2, 5, 7, CXCR2 or 4 (cell-specific or conditional) will be subject to vascular injury, intravital perfusion or 2-photon microscopy or bone marrow transplantation (Reviews: Weber et al., ATVB 2004; Weber, Circ. Res. 2005; von Hundelshausen & Weber, Circ. Res.; Funding: DFG FOR809/TP2-4). Macrophage migration inhibitory factor in atherosclerosis and inflammation The cytokine macrophage migration inhibitory factor (MIF) plays a critical role in inflammatory diseases and atherogenesis. However, its molecular mode of action is only incompletely understood. For instance, a specific and typical receptor has not yet been identified, and the signaling pathways beyond its intracellular interaction with JAB-1, e.g. ERK/MAP kinase activation, and its functions in vascular cell recruitment remain to be elucidated. In cooperation with Dr. Bernhagen, we identified the chemokine receptors CXCR2 and CXCR4 as functional high-affinity receptors for MIF. MIF triggers G_i- and integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin activation and calcium influx through CXCR2 or CXCR4. MIF competes with cognate ligands for CXCR4 and CXCR2 binding, and directly binds to CXCR2. CXCR2 and the MIF-binding surface protein CD74 (invariant chain) forms a receptor complex, and monocyte arrest elicited by MIF in inflamed or atherosclerotic arteries involved both CXCR2 and CD74. In vivo, MIF deficiency impaired monocyte adhesion to the arterial wall in atherosclerosis-prone mice, and MIF-induced leukocyte recruitment required Cxcr2. Blockade of MIF but not canonical ligands of CXCR2 or 4 in mice with advanced atherosclerosis led to plaque regression and reduced monocyte and T-cell content in plaques. Blocking MIF also conferred a more stable phenotype to neointimal plaques. By activating both CXCR2 and CXCR4, MIF displays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis. Targeting MIF in individuals with manifest atherosclerosis can be used to treat this condition. We will address the exact composition and function of the MIF receptor complex, which may be composed of CXCR2/CXCR4 heterodimers with CD74 but also CD44-linked src kinase, and the structure-function relationship of MIF, which contains an pseudo-elr-motif reminiscent of CXCR2 ligands (References: e.g. Schober et al., Circulation 2004; Bernhagen et al. & Weber, Nat. Med. 2007; Zernecke, Weber et al. & Bernhagen & Weber, PNAS 2008; Funding: DFG FOR809/TP1).

11 Curriculum vitae - Prof. Dr. Christian Weber 11 Mechanisms of vascular progenitor recruitment and homeostasis: role of CXCL12/CXCR4 Adult bone-marrow derived stem cells display a remarkable capacity for differentiation into various cell types and may thereby support tissue regeneration. Vascular progenitor cells giving rise to both endothelial or smooth muscle cells (SMCs) are not only critical in vasculogenesis but also involved in vascular disease/remodeling, playing pathogenic or protective roles in atherosclerosis, restenosis and transplant vasculopathy. The chemokine stromal cell-derived factor-1α/cxcl12 mediates the mobilization and engraftment of hematopoietic stem cells and is important in tissue repair and vessel formation. Less is known about molecular mechanisms of vascular progenitor cell recruitment and the role of chemokines therein. After arterial injury, an inhibition of plaque area and SMC content in atherosclerosis-prone mice repopulated with LacZ+ or CXCR4-/- bone marrow or lentiviral transfer of an antagonist revealed a crucial involvement of local CXCL12 and its receptor CXCR4 in neointimal hyperplasia and recruitment of bone marrow-derived SMC progenitors (SPCs). CXCL12 expression in medial SMCs is preceded by apoptosis and inhibited by blocking caspase-dependent apoptosis. CXCL12 presented on matrix-adherent platelets triggers CXCR4- and Pselectin-dependent arrest of progenitor cells at the site of injury, preferentially mobilizes and recruits c-kit-/pdgfr-β+/lineage-/sca-1+ SPCs to the neointima. Thus, the CXCL12/CXCR4 axis is pivotal for vascular remodelling, epitomizing its importance for tissue repair and identifying a target to prevent neointima formation. In contrast, the recruitment of bone marrow-derived endothelial progenitor cells (EPCs) from the circulation involved the chemokines CXCL1 and CXCL7, and their receptor CXCR2 on a CD14+ KDR+ EPC subset to accelerate endothelial recovery and limit neointima formation. Using a CXCR4 antagonist, lentiviral transfer of CXCR4 degrakine or CXCR4-/- bone marrow chimeras in an Apoe- /- background revealed that the CXCL12/CXCR4 axis protects against primary atherosclerosis by controling neutrophil homeostasis, unveiling a general importance of neutrophils in atherogenesis. We will assess the relevance of these mechanisms, e.g. apoptosis-related CXCL12 induction, the nature of EPC and SPC subsets and their recruitment, at distinct stages of atheroprogression and instability by vascular cell typespecific and inducible deletion of CXCR4. These data will provide valuable clues to a selective control of progenitor cell trafficking and homeostasis in vascular remodeling (References: Zernecke et al., Circ. Res. 2005; Hristov et al., Circ. Res. 2007; Zernecke et al., Circ. Res. 2008; Funding: DFG FOR809/TP4/ZP). Function of junctional adhesion molecule-a (JAM-A) in inflammation and atherogenesis JAM-A is a member of the immunoglobulin superfamily and expressed at the apical region of the tight juntions of epi- and endothelial cells, where it engages in homophilic interactions via its N-terminal domain with JAM-A present on neighbouring cells. Via its cytoplasmatic PDZ domains, JAM-A is anchored to the actin cytoskeleton. Thus, JAM-A regulates endothelial cell permeability although it is redistributed towards the cell surface upon inflammatory stimuli. We have identified heterophilic interactions of JAM-A (via its membraneproximal domain) with the leukocyte αlβ2 integrin (LFA-1) and its role in the adhesion and transendothelial migration of lymphocytes. In addition, homophilic JAM-A binding appears to be involved in cell interactions on endothelium. We study the exact localisation of relevant structural regions and binding epitopes for the heterophilic interaction between LFA-1 and JAM-A, as well as the kinetics for this interaction. This is accomplished by using purified (domain-deleted) JAM-A/immunoglobulin fusion proteins and isolated I-domain of L locked in the open, high-affinity conformation in solid phase binding or surface plasmon resonance experiments. An involvement of metal-ion-binding acidic amino acids and N-linked glycosylation sites is explored by site-directed mutagenesis. The discplacement of homophilic JAM-A interactions by heterophilic interactions with the active I-domain as defined by atomic force microscopy implies a molecular zipper mechanisms during transendothelial diapedesis. The dynamic regulation of heterophilic JAM-A/LFA-1 interactions during transendothelial migration is investigated using fluorescently labeled JAM-A or LFA-1 proteins, or mutants lacking their cytoplasmatic domains in confocal and wide field fluorescent microscopy. Lateral interactions of LFA-1 and JAM-A in cis will be examined using fluorescent resonance energy transfer (FRET) and coimmunoprecipitation experiments. Primary atherosclerosis will be investigated in JAM-A-/-Apoe-/- double-knockout mice, endothelial-specific JAM-A-/- deletion and JAM-A-/- bone marrow chimeras. The function of JAM-A in monocyte recruitment to early lesions or denuded vessels is studied in ex vivo/in vivo perfusion models using 2-photon microscopy. This will deepen our knowledge about the structural determinants and functional role of JAM-A interactions (References: e.g. Ostermann et al. & Weber, Nat. Immunol. 2002; Weber et al., Nat. Rev. Immunol. 2007; Funding: DFG FOR809/TP6). Endothelial progenitor cells and statins in cardiovascular risk and myocardial regeneration Bone marrow contains a subtype of progenitor cells, which display the capacity to migrate to the peripheral circulation and to differentiate into mature endothelial cells and have thus been termed endothelial progenitor cells (EPCs). In general, EPCs are characterized by the expression of CD133, CD34, and VEGF receptor-2 (KDR, Flk-1), and acquire expression of CD31 or VE-cadherin during differentiation. While EPCs may be useful to support vasculogenesis and angiogenesis to improve ischemic conditions, as suggested by initial clinical trials, their value for risk prediction in atherosclerotic vascular disease is explored. In a program grant, we will investigate the complexity of multiple aspects in the application of EPCs for analysis, prognosis and potential therapies of cardiovascular disease. We have found that reduced numbers of

12 Curriculum vitae - Prof. Dr. Christian Weber 12 circulating EPCs in patients with coronary artery disease was associated with long-term statin treatment. In prospective trials, we will evaluate the potential of EPC versus SPC levels to predict restenosis after coronary stent placement, transplant arteriopathy or outcome after myocardial infarction. In mice with tie-2- GFP+, CCR2-/- or CXCR4-/-bone marrow or after injection of sorted sca-1+lin-flk+ EPCs, we will assess the functions of endogenous EPCs in tissue regeneration after myocardial infarction. We will further develop novel proendothelial peptide coatings (e.g. polyethelynglycol with cyclic RGD or KC mimetics) of shapememory polymer stents to accelerate reendothelialization by EPC recruitment and to limit in-stent restenosis in miniaturized formats for implantation in murine aortas or carotid arteries, allowing first studies in transgenic mice. On the other hand, we will explore the benefit of statins in improving survival and protecting against myocardial dysfunction in murine models of infarction or sepsis (Reviews: Hristov & Weber, J. Cell. Mol. Med. 2004;8:498; Merx & Weber, Circulation 2007;116:782; Funding: IZKF VVB113). Structure-function-analysis of the chemokine-interactome in atherosclerosis This highly interdisciplinary and multinational project is focused on the role of chemokine heteromers in the inflammatory pathogenesis of atherosclerosis. Chemokines, which can also be stored or deposited by platelets, are instrumental in orchestrating inflammatory cell recruitment to the arterial wall, yet to date there is no specific anti-atherogenic therapeutic option without side-effects on the immune system. We have recently introduced the new paradigm that chemokine heteromerization provides the combinatorial diversity to allow for functional plasticity and regulatory fine-tuning, coining this interactome. More recently, we could also demonstrate the in vivo relevance of chemokine heteromerization for the first time. Our hypothesis aims to exploit this functional chemokine interactome not only as a new biological principle but also as an anti-inflammatory approach to selectively target atherosclerosis. How can this be accomplished? First we will structurally characterize recombinant chemokine heteromers and their mode of interaction of using NMR, fluorescence or CD spectroscopy and combine this with molecular dynamics simulation to obtain structural models as shown with the highest free energy for the prototype CCL5-CXCL4 interaction. Its high affinity of 50 nm is due to negatively charged CXCL4 N-terminus wrapping around its counterpart to extend to the positive central β-sheets of CCL5. Using such models, we design and synthesize obligate heteromers using linkers and tboc coupling chemistry for various chemokine pairs. We will reconstitute mice deficient in these proteins with obligate heteromers to monitor their effects on atherosclerosis and half-life in vivo. We will also generate mice with novel genetic deletions or knock-in of chemokine mutants with defective interactions. Conversely, we will design and synthesize stabilized cyclic β-hairpin peptides to specifically disrupt heteromer formation such as MKEY. These can be employed to reveal an in vivo relevance of such interactions by therapeutically limiting atherosclerosis or for imaging atherosclerotic plaques when fluorescently labeled. From our initial studies, we have no evidence for immune-related side-effects. Finally, we will use antibodies specifically directed against or disrupting heteromers, which will also be evaluated as biomarkers in patients. This is translated into drug development of biological therapeutics, and diagnostic markers and theragnostic applications for clinical use. (Carolus Inc, Koenen et al., Nat. Med. 2009). It will be a future goal to consequently explore and pursue these areas of interest into further (sub-) molecular depth for detailed appreciation of their functional interactions, by implementing more refined biophysical and structural biology methods, namely NMR and IFT, as outlined above, molecular dynamics simulation and crystallography, but also through establishing and employing complex mouse models carrying transgenes under cell-specific and conditional control, to improve visualization e.g. by 2-photon microscopy in vivo, or to modulate and operate genetic and cellular programs / functions, probing their pathophysiological relevance. Role of micrornas in atherosclerosis and metabolic syndrome Vascular disease, such as atherosclerosis, is highly prevalent in metabolic syndrome MetS. This is due to the enhanced adipocyte and vascular inflammation that occurs in MetS. Understanding the complex etiology of vascular disease in MetS will allow the design of effective therapies to prevent and treat this debilitating disease. Recently, micrornas (mirs) have been shown to be altered in atherosclerosis. For example, we found using a mirnomics approach that several micrornas (mir-126, mir-146, mir-155) are enhanced in atherosclerosis plaques, while others are down-regulated (mir-181a). Additionally, we have found that a subset of mirs are packaged in secreted microvesicles (MVs) and have evidence that this packaging may be altered in disease states. A single nucleotide polymorphism (SNP) in mir-146a was associated with CAD in a large patient population. MicroRNAs are attractive targets for therapeutic modulation. However, the functional role of individual mirs in the development of atherosclerotic lesions is largely unknown. We will exploit our mirnomics data to test the functional role of four mirs (mir-126, mir-146, mir-155, and mir-181a) in the pathogenesis of atherosclerosis in the context of MetS. This includes analysis of pro- and anti-atherogenic effects of mirs on the inflammatory response in macrophages. The contribution of mirs to endothelial dysfunction, which is important in early atherosclerosis, in response to atherogenic stimuli will be evaluated. Moreover, the role and molecular mechanism of dysfunctional mir packaging into endothelial MVs in MetS-associated atherosclerosis and its regulation under conditions of disturbed flow and at predilection sites will be studied. The identification of mirs involved in accelerated atherosclerosis promises to define a new class of targets in the treatment and prevention of this detrimental sequela of the MetS.

13 Curriculum vitae - Prof. Dr. Christian Weber 13 Bibliography 10 most important original articles 1. von Hundelshausen P, Weber KSC, Huo YQ, Proudfoot A, Nelson PJ, Ley K, Weber C (2001) Deposition of RANTES by platelets triggers monocyte recruitment on inflamed and atherosclerotic endothelium. Circulation 103: Ostermann G, Weber KSC, Zernecke A, Schröder A, Weber C (2002) JAM-1 is a ligand for the 2 integrin LFA-1 involved in transendothelial migration of leukocytes. Nature Immunol. 3: Huo YQ, Schober A, Forlow SB, Smith D, Hyman M, Jung S, Littman DR, Weber C, Ley K (2003) Circulating activated platelets exacerbate atherosclerosis in apolipoprotein E deficient mice. Nature Med. 9: Zernecke A, Schober A, von Hundelshausen P, Liehn EA, Möpps B, Mericskay M, Gierschik P, Biessen EA, Weber C (2005) SDF-1 /CXCR4 is instrumental for neointimal hyperplasia and recruitment of smooth muscle cell progenitors. Circ. Res. 96: Bernhagen J, Krohn R, Lue H, Gregory JL, Zernecke A, Koenen RR, Dewor M, Georgiev I, Schober A, Leng L, Kooistra T, Fingerle-Rowson G, Ghezzi P, Kleemann R, McColl SR, Bucala R, Hickey MJ, Weber C (2007) MIF is a non-cognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment. Nature Med. 13: (comment in Nature Rev. Drug Dis. 6:435) 6. Zernecke A, Bot I, Djalali Talab Y, Shagdarsuren E, Meiler S, Liehn EA, Schober A, Soehnlein O, Sperandio M, Tacke F, Biessen EA, Weber C (2008) Protective role of Cxcr4/Cxcl12 unveils the importance of neutrophils in atherosclerosis. Circ. Res. 102: Choi EY, Chavakis E, Czabanka M, Langer H, Fraemohs L, Economopoulou M, Orlandi A, Kundu R, Zheng Y, Ballantyne C, Constant S, Aird W, Papayannopoulou T, Gahmberg C, Udey M, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T (2008) Del-1 is a endogenous inhibitor of leukocyte-endothelial adhesion preventing inflammatory cell recruitment. Science 322: Koenen RR, von Hundelshausen P, Nesmelova IV, Zernecke A, Liehn EA, Sarabi A, Kramp BK, Piccinini A, Kowalska A, Kungl AJ, Hackeng TM, Mayo KH, Weber C (2009) Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice. Nature Med. 15: Zernecke A, Bidzhekov K, Noels H, Shagdarsuren E, Gan L, Denecke B, Hristov M, Köppel T, Nazari Jahantigh M, Lutgens E, Wang S, Olson E, Schober A, Weber C (2009) Delivery of microrna-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci. Signal. 2:ra Weber C, Meiler S, Döring Y, Koch M, Drechsler M, Megens R, Rowinska Z, Bidzhekov K, Fecher C, Ribechini E, van Zandvoort M, Binder C, Jelinek Y, Hristov M, Boon L, Jung S, Korn T, Lutz M, Förster I, Zenke M, Hieronymus T, Junt T, Zernecke A (2011) CCL17-expressing dendritic cells drive atherosclerosis by restraining regulatory T-cell homeostasis in mice. J. Clin. Invest. 121: Bibliometric data and criteria (Scopus January 28, 2014) Cumulative Impact factor (Original and review articles): Cumulative Impact factor (Original articles including #245): Cumulative Impact factor (100 Original articles as first or last author): Cumulative Impact factor (Review articles including #135): Average Impact factor per Original article: 8.0 Average Impact factor per Original article (First or Last author): 8.7 Total citations Average citations per published article 52 citations citations citations citations citations citations h-index (Hirsch, Proc. Natl. Acad. Sci. 2005;102:16569; Nature 2007;448:737) 71 m-index = h-index per years of scientific activity 3.1 h-index (First or Last author) 59 h-index (Harzing publish or perish) 80

14 Curriculum vitae - Prof. Dr. Christian Weber 14 Original articles Cum. Impact Weber C, Aepfelbacher M, Lux I, Zimmer B, Weber PC (1991) Docosahexaenoic acid inhibits PAF and LTD4 stimulated [Ca 2+ ] i -increaseh in differentiated monocytic U937 cells. Biochim. Biophys. Acta. 1133: (Impact 4.134) 2. Ziegler-Heitbrock HWL, Käfferlein E, Haas JG, Meyer N, Ströbel M, Weber C, Flieger D (1992) Gangliosides suppress tumor necrosis factor production in human monocytes. J. Immunol. 148: (Impact 5.520) 3. Weber C, Aepfelbacher M, Haag H, Ziegler-Heitbrock HWL, Weber PC (1993) Tumor necrosis factor induces enhanced responses to platelet activating factor and differentiation in human monocytic Mono Mac 6 cells. Eur. J. Immunol. 23: (Impact 4.970) 4. Weber C, Kruse HJ, Sellmayer A, Erl W, Weber PC (1993) Platelet activating factor enhances receptoroperated Ca 2+ -influx and subsequent prostacyclin-synthesis in human endothelial cells. Biochem. Biophys. Res. Commun. 195: (Impact 2.406) 5. Ziegler-Heitbrock HWL, Sternsdorf, Liese J, Belohradsky B, Weber C, Wedel A, Schreck R, Baeuerle P, Ströbel M (1993) Pyrrolidine-dithiocarbamate inhibits NF- B mobilization and TNF production in human monocytes. J. Immunol. 151: (Impact 5.520, 266 citations) 6. Sellmayer A, Goeßl C, Obermeier H, Volk R, Reeder E, Weber C, Weber PC (1994) Differential expression of eicosanoid synthesis in monocytic cells treated with retinoic acid and 1,25-dihydroxy-vitamin D 3. Prostaglandins. 47: (Impact 2.732) 7. Ziegler-Heitbrock HWL, Schraut W, Wendelgaß P, Ströbel M, Sternsdorf T, Weber C, Aepfelbacher M, Haas JG (1994) Distinct patterns of differentiation induced in the monocytic cell line Mono Mac 6. J. Leukoc. Biol. 55: (Impact 4.568) 8. Weber C, Erl W, Pietsch A, Ströbel M, Ziegler-Heitbrock HWL, Weber PC (1994) Antioxidants inhibit monocyte adhesion by suppressing nuclear factor- B mobilization and induction of vascular cell adhesion molecule 1 in endothelial cells stimulated to generate radicals. Arterioscler. Thromb. Vasc. Biol. 14: (Impact 6.338, 292 citations) 9. Haag H, Grünberg B, Weber C, Vauti F, Aepfelbacher M, Siess W (1994) Lovastatin inhibits receptor-stimulated Ca 2+ -influx of retinoic acid differentiated U937 and HL-60 cells. Cell. Signal. 7: (Impact 4.304) 1995 Cum. Impact Weber C, Erl W, Weber PC (1995) Enhancement of monocyte adhesion to endothelial cells by modified low density lipoprotein is mediated via activation of CD11b. Biochem. Biophys. Res. Commun. 206: (Impact 2.406) 11. Weber C, Calzada-Wack JC, Goretzki M, Pietsch A, Johnson JP, Ziegler-Heitbrock HWL (1995) Retinoic acid inhibits basal and interferon- induced expression of intercellular adhesion molecule 1 in monocytic cells. J. Leukoc. Biol. 57: (Impact 4.568) 12. Erl W, Weber C, Wardemann C, Weber PC (1995) Adhesion properties of Mono Mac 6, a monocytic cell line with characteristics of mature human monocytes. Atherosclerosis 113: (Impact 3.706) 13. Weber C, Erl W, Pietsch A, Weber PC (1995) Aspirin inhibits NF- B mobilization and monocyte adhesion in stimulated human endothelial cells. Circulation. 91: (Impact , 201 citations) 14. Weber C, Erl W, Pietsch A, Danesch U, Weber PC (1995) Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule 1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-. Arterioscler. Thromb. Vasc. Biol. 15: (Impact 6.338, 129 citations) 15. Weber C, Negrescu E, Erl W, Pietsch A, Frankenberger M, Ziegler-Heitbrock HWL, Siess W, Weber PC (1995) Inhibitors of protein tyrosine kinase suppress TNF-stimulated induction of endothelial cell adhesion molecules. J. Immunol. 155: (Impact 5.520) 16. Pietsch A, Weber C, Goretzki M, Weber PC, Lorenz RL (1995) N-3 but not n-6 fatty acids reduce the expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells. Cell Biochem. Funct. 13: (Impact 1.854) 17. Weber C, Erl W, Weber PC (1995) Lovastatin induces differentiation of Mono Mac 6 cells. Cell Biochem. Funct. 13: (Impact 1.854)

15 Curriculum vitae - Prof. Dr. Christian Weber Cum. Impact Weber C, Erl W, Weber K, Weber PC (1996) Increased adhesiveness of isolated monocytes to en-dothelium is prevented by vitamin C intake in smokers. Circulation 93: (Impact , 134 citations) 19. Weber C, Alon R, Moser B, Springer TA (1996) Sequential regulation of 4 1 and 5 1 integrin avidity by CC chemokines in monocytes: Implications for transendothelial chemotaxis. J. Cell Biol. 134: (Impact , 180 citations) 20. Weber C, Kitayama J, Springer TA (1996) Differential regulation of 1 and 2 integrin avidity by chemoattractants in eosinophils. Proc. Natl. Acad. Sci. USA. 93: (Impact 9.737, 167 citations) 1997 Cum. Impact Sellmayer A, Obermeier H, Weber C (1997) Intrinsic cyclooxygenase activity is not required for monocytic differentiation of U937 cells. Cell Signal. 9: (Impact 4.304) 22. Erl W, Weber C, Wardemann C, Weber PC (1997) -Tocopheryl succinate inhibits monocytic cell adhesion to endothelial cells by suppressing NF- B mobilization and adhesion molecule expression. Am. J. Physiol. 273: H634-H640. (Impact 3.711) 23. Weber C, Lu CF, Casasnovas JM, Springer TA (1997) Role of L 2 integrin avidity in transendothelial chemotaxis of mononuclear cells. J. Immunol. 159: (Impact 5.520) 24. Kupatt C, Weber C, Wolf DA, Becker BF, Smith TW, Kelly RA (1997) Nitric oxide attenuates reoxygenationinduced ICAM-1 expression in coronary microvascular endothelium: role of NF- B. J. Mol. Cell. Cardiol. 29: (Impact 5.148) 25. Weber C, Springer TA (1997) Neutrophil accumulation on activated, surface-adherent platelets in flow is mediated by interaction of Mac-1 with fibrinogen bound to IIb 3 and stimulated by platelet activating factor. J. Clin. Invest. 100: (Impact , 198 citations) 26. Weber C, Erl W, Weber KSC, Weber PC (1997) HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of monocytes to endothelium and reduce increased adhesiveness of monocytes isolated from hypercholesterolemic patients. J. Am. Coll. Cardiol. 30: (comment in J. Am. Coll. Cardiol. 30:1218). (Impact , 289 citations) 27. Kupatt C, Habazettl H, Zahler S, Weber C, Becker BF, Messmer K, Gerlach E (1997) ACE inhibition prevents leukocyte-dependent reperfusion injury by reducing coronary leukocyte adhesion. Cardiovasc. Res. 36: (Impact 5.940) 1998 Cum. Impact Piali L, Weber C, La Rosa G, Mackay CR, Springer TA, Clark-Lewis I, Moser B (1998) The chemokine receptor CXCR3 mediates rapid and shear-resistant adhesion-induction of effector T lymphocytes by the chemokines IP10 and Mig. Eur. J. Immunol. 28: (Impact 4.970, 164 citations) 29. Erl W, Weber PC, Weber C (1998) Monocytic cell adhesion to endothelial cells stimulated by oxidized low density lipoprotein is mediated by distinct endothelial ligands. Atherosclerosis. 136: (Impact 3.706) 30. Weber KSC, Klickstein L, Weber PC, Weber C (1998) Chemokine-induced monocyte transmigration requires cdc42-mediated cytoskeletal changes. Eur. J. Immunol. 28: (Impact 4.970) 31. Weber C, Springer TA (1998) Interaction of VLA-4 with VCAM-1 supports transendothelial che-motaxis of monocytes by facilitating lateral migration. J. Immunol. 161: (Impact 5.520) 1999 Cum. Impact Neuzil J, Sorensen I, Weber T, Weber C, Brunk U (1999) Tocopheryl succinate-induced apoptosis of Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation. FEBS Lett. 445: (Impact 3.582) 33. Weber KSC, von Hundelshausen P, Weber PC, Clark-Lewis I, Weber C (1999) Differential chemokine immobilization and hierarchical involvement of their receptors in monocyte arrest and transmigration on inflammatory endothelium. Eur. J. Immunol. 29: (Impact 4.970, 148 citations)

16 Curriculum vitae - Prof. Dr. Christian Weber Draude G, von Hundelshausen P, Frankenberger M, Ziegler-Heitbrock HWL, Weber C (1999) Distinct scavenger receptor expression and function in the CD14 + CD16 + human blood monocyte subsets. Am. J. Physiol. 276:H1144-H1149. (Impact 3.711) 35. Erl W, Hansson GK, de Martin R, Draude G, Weber KSC, Weber C (1999) Nuclear factor- B regulates apoptosis and inhibitor of apoptosis protein-1 expression in vascular smooth muscle cells. Circ. Res. 84: (Impact , 126 citations) 36. Weber KSC, Klickstein LB, Weber C (1999) Specific activation of the 2 integrins Mac-1 and LFA-1 by chemokines in mononuclear cells mediated by distinct activation pathways via the subunit cytoplasmic domains. Mol. Biol. Cell. 10: (Impact 4.604) 37. Weber KSC, Draude G, Erl W, de Martin R, Weber C (1999) Monocyte arrest and transmigration on inflamed endothelium in shear flow is inhibited by adenoviral gene transfer of I B-. Blood 93: (Impact 9.060) 38. Weber C, Draude G, Weber KSC, Wübert J, Lorenz R, Weber PC (1999) Downregulation by tumor necrosis factor- of monocyte CCR2 expression and MCP-1-induced transendothelial chemotaxis is antagonized by oxidized LDL: a potential mechanism of monocyte retention in atherosclerotic lesions. Atherosclerosis 145: (Impact 3.706) 39. Gröne HJ, Weber C, Weber KS, Gröne EF, Rabelink J, Klier C, Wells TN, Proudfoot A, Schlöndorff D, Nelson PJ (1999) MetRANTES reduces vascular and tubular damage during acute vascular rejection: blocking monocyte arrest and recruitment. FASEB J. 13: (Impact 5.704, 185 citations) 40. Weber KSC, Nelson PJ, Gröne HJ, Weber C (1999) Expression of CCR2 by endothelial cells: implications for MCP-1-mediated wound injury repair and in vivo inflammatory activation of endothelium. Arterioscler. Thromb. Vasc. Biol. 19: (Impact 6.338, 162 citations) 2000 Cum. Impact Weber C, Belge KU, von Hundelshausen P, Draude G, Steppich B, Mack M, Frankenberger M, Weber KSC, Ziegler-Heitbrock HWL (2000) Differential chemokine receptor expression and function in human monocyte subpopulations. J. Leukoc. Biol. 67: (Impact 4.568, 170 citations) 42. Erl W, Weber C, Hansson GK (2000) Susceptibility to apoptosis induced by pyrrolidine dithiocarbamate is dependent on cell type, density and copper/zinc ions. Am. J. Physiol. Cell Physiol. 278:C (Impact 3.711) 2001 Cum. Impact Neuzil J, Weber T, Gellert N, Weber C (2001) Selective cancer cell killing by -tocopheryl succinate. Brit. J. Cancer 84: (Impact 5.082, 125 citations) 44. Neuzil J, Weber T, Schröder A, Lu M, Olejnicka B, Ostermann G, Gellert N, Mayne GC, Negre-Salvayre A, Sticha M, Coffey RJ, Weber C (2001) Induction of cancer cell apoptosis by -tocopheryl succinate: molecular pathways and structural requirements. FASEB J. 15: (Impact 5.704, 172 citations) 45. Weber C, Weber KSC, Klier C, Gu H, Horuk R, Wank R, Nelson PJ (2001) Specialized roles of the chemokine receptors CCR1 and CCR5 in recruitment of monocytes and Th1-like/CD45RO + T cells. Blood 97: (comment in Blood 97:833). (Impact 9.060, 135 citations) 46. Horuk R, Clayberger C, Krensky AM, Wang Z, Gröne HJ, Weber C, et al. (2001) A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J. Biol. Chem. 276: (Impact 4.651) 47. von Hundelshausen P, Weber KSC, Huo YQ, Proudfoot A, Nelson PJ, Ley K, Weber C (2001) Deposition of RANTES by platelets triggers monocyte recruitment on inflamed and atherosclerotic endothelium. Circulation 103: (comment in Circulation 103:1718). (Impact , 280 citations) 48. Neuzil J, Schröder A, von Hundelshausen P, Zernecke A, Weber T, Gellert N, Weber C (2001) Inhibition of endothelial inflammatory responses by subapoptotic caspase activation and p65 cleavage. Biochemistry 40: (Impact 3.377) 49. Zernecke A, Weber KSC, Erwig LP, Kluth DC, Schröppel B, Rees A, Weber C (2001) Combinatorial model of chemokine involvement in glomerular monocyte recruitment: role of CXCR2 in infiltration during nephrotoxic nephritis. J. Immunol. 166: (Impact 5.520)

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