Chronicle of the Albrecht Hasinger Lecture
Since 1994 the Albrecht-Hasinger-Lecture commemorates the achievements of Albrecht Hasinger in the German health care system, especially in rheumatology. Abrecht Hasinger was State Secretary for Health. He was one of the founding fathers of the DRFZ and the first president of the board of trustees from 1988 until 1993.
The future of HSCT for Multiple sclerosis and systemic sclerosis
Richard K. Burt pioneered the use of hematopoietic stem cells to treat autoimmune diseases, including Multiple Sclerosis, Crohn´s Disease or lupus. Today, Dr. Burt’s stem cell work has been recognized as one of the top 10 advances since the beginning of the 21st century. Immune ablation followed by autologous hematopoietic stem cell transplantation has emerged as promising treatment option for patients with severe forms of autoimmune diseases refractory to conventional therapies. As Chief of Immunotherapy and Autoimmune Diseases in the Department of Medicine, he is and was the leader of numerous randomized, controlled stem cell trials. Currently studies for Systemic Sclerosis and for Multiple Sclerosis are ongoing.
The biology of Interleukin-6 and its role in autoimmunity
Cytokines receptors exist in membrane bound and soluble form. The IL-6/soluble IL-6R complex stimulates target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. We have named this process ‘trans-signaling’. The soluble IL-6R is generated via ectodomain shedding by the membrane bound metalloprotease ADAM17 but also by other proteases. The soluble gp130 protein is the natural inhibitor of IL-6/soluble IL-6R complex responses [1, 2]. A dimerized recombinant soluble gp130Fc fusion protein is a molecular tool to discriminate between gp130 responses via membrane bound and soluble IL-6R responses.
Interestingly, depending on the animal model used, global blockade of IL-6 signaling by neutralizing monoclonal antibodies and selective blockade of IL-6 trans-signaling can lead to drastically different consequences. We used neutralizing monoclonal antibodies for global blockade of IL-6 signaling and the sgp130Fc protein for selective blockade of IL-6 trans-signaling in several animal models of human diseases. Defense against bacterial infections rely on the membrane bound IL-6R . Blocking IL-6 trans-signaling via sgp130Fc inhibited liver cancer formation.
The extent of inflammation is controlled by trans-signaling via the soluble IL-6R. Using the sgp130Fc protein or sgp130Fc transgenic mice we demonstrate in animal models of inflammatory bowel disease, peritonitis, rheumatoid arthritis, atherosclerosis, pancreatitis, lupus erythematodes, colon cancer, ovarian cancer, pancreatic cancer and lung cancer that IL-6 trans-signaling via the soluble IL-6R is the crucial step in the development and the progression of the disease [1-6]. Therefore, sgp130Fc is a novel therapeutic agent for the treatment of chronic inflammatory diseases and cancer and it underwent phase I clinical trials as an anti-inflammatory in 2013/2014. Phase II clinical trials started in late 2016.
The elusive search for a target in osteoarthritis therapy: Lessons from in vitro and in vivo models
Mary B. Goldring, PhD, is Senior Scientist and Co-Director of the Tissue Engineering, Regeneration and Repair Program in the Research Division of the Hospital for Special Surgery and Professor of Cell and Developmental Biology, Weill Cornell Medical College in New York City. Her research on cartilage biology focuses on the molecular regulation of extracellular matrix remodeling. Her major contributions include the identification of the molecular and cellular mechanisms involved in the pathogenesis of osteoarthritis and rheumatoid arthritis and the development of in vitro models for the study of human chondrocyte biology. Current work involves relating findings in mouse models of osteoarthritis to aspects of the human disease.
“Osteoarthritis (OA) is a whole joint disease, in which thinning and loss of cartilage is a critical determinant in OA progression. The disruption of cartilage homeostasis due to multiple potential causes, related to aging, genetic predisposition, trauma, or metabolic disorder, is associated with profound phenotypic modifications of chondrocytes. Early changes involve disruption of the pericellular matrix through signaling events mediated by chondrocyte receptors such as discoidin domain receptor-2 (DDR-2) and syndecan-4. My laboratory studies the mechanisms of gene regulation by which stress- and inflammation-induced signals induce expression of matrix metalloproteinase 13 (MMP-13), the pivotal collagen-degrading proteinase that marks osteoarthritis progression, as well as other catabolic and anabolic responses in cartilage and other joint tissues. Common mediators of these processes in human OA cartilage are also involved in mechano-transduction, including the protein kinases, IKKs and MAPKs. These pathways converge on transcriptional regulation of MMP13, IL1B, and other key genes by NF-kB, Elf3, C/EBPb, Runx2, and hypoxia-inducible factor (HIF) 2a. Alterations in the methylation status of specific CpG sites in the promoters of MMP13, IL1B, NOS2, and COL9A1 are also associated with aberrant gene expression in OA cartilage. Current work involves relating findings in mouse models of osteoarthritis to aspects of the human disease by examining knockout and transgenic mouse strains in the context of a post-traumatic OA mouse model due to surgical destabilization of the medial meniscus (DMM). Novel mouse strains have been generated in which the cytokine-inducible transcription factor Elf3 is either knocked out specifically in cartilage (Col2a1Cre;Elf3fl/fl) or overexpressed in cartilage and synovium (Comp-tTA;TRE-Elf3). Current efforts are profiling gene expression (RNAseq) and microRNAs over the course of disease initiation and progression in novel mouse strains with inducible, cartilage-specific deletion of the NF-kB signaling kinases, IKKa and IKKb, compared to the Runx2+/- mouse, which is protected from DMM-OA, and the Col11a1+/- (Cho/+; chondrodysplasia) mouse that develops accelerated OA with aging. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and participate in matrix destruction and abnormal repair in OA may lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair.” [Mary B. Goldring]
Mechanisms of information transfer at immunological synapses
The adaptive immune response depends on the cellular interaction of T cells with their specific antigen on antigen presenting cells. This interaction happens in the nanometer scale and is defined as the immunological synapse. If the signaling is appropriately regulated, the host is protected against a broad spectrum of pathogen and cultivates productive close interactions with many commensal microbes. Errors in these interactions or their interpretation can lead to pathogen escape at one extreme or autoimmunity and inflammatory diseases at the other extreme. Key therapeutics such as anti- CTLA-4 and anti-PD-1 are known to modulate immunological synapses for cancer therapy. Future studies will focus on a systematic screen for immunological synapse modulators with therapeutic applications.
This immunological synapse, the intercellular communication platform of the immune system, is a key to health and has been the focus of Professor Dustin´s work over the past 30 years.
The focus of my lab is the study of the immunological synapse. I have 30 years experience with membrane protein purification beginning with work on ICAM-1, CD58 and LFA-1 as a student with Timothy Springer. I have over 25 years of experience with supported planar bilayers as a platform for fluorescence microscopy of molecular interactions at membrane interfaces and immunological synapses. My lab has also analyzed the immunological synapse in vivo through two-photon laser scanning microscopy. I have 15 years experience in this area with papers published on imaging in lymph nodes, liver, kidney, brain, spinal cord, spleen, small intestines, bone marrow and solid tumors. I have collaborated extensively with Dr. Hioe, publishing several papers together on gp120 interactions with receptors on live T cells and analysis of T cell receptor enriched extracellular vesicles in the immunological synapse.
Reconstruction of the Joint: from Development to Engineering
When we seek to repair damaged joints, two major approaches are possible, i.e. enhancing endogenous repair mechanisms and/or extrinsic repair. Endogenous (intrinsic) repair may be targeted in different phases of tissue healing including the use of methods/surgical procedures or compounds affecting inflammation, debris removal and cell recruitment, followed by stimulation of cell proliferation, differentiation and tissue formation. When intrinsic repair is insufficient or inappropriate, in the latter case leading to scar tissue formation, extrinsic repair needs to be considered, i.e. tissue engineering approaches. These include growth factor formulations, smart biomaterials, cell populations and more powerfull combination products that drive tissue repair and support and guide locally the tissue regeneration processes. Much of the succes of these strategies is also dependent on the microenvironment, and thus on the understanding of the local cellular and molecular processes in the affected joint.
An overview will be presented of the existing and evolving strategies seeking to repair damaged joints. They include cell based treatments such as autologous chondrocyte implantation, and variations thereof, and the use of stem cell populations. Major challenges are encountered in case of deeper osteochondral defects and the reconstruction of full joints triggering novel avenues for tissue engineered solutions. We still face a lack of understanding the developmental, cell and molecular biology of the diarthrodal joint, preventing us to take a scientifically sound developmental engineering approach. New enabling technologies are required to translate this into robust manufacturing processes of these 3D products classified as Advanced Therapeutic Medicinal Products (ATMP). Some future trends will be discussed including ongoing efforts to make biological joints.
Frank P. Luyten, MD, PhD is board certified Rheumatologist, tenured full Professor and Head of the Division of Rheumatology at the University Hospitals Leuven; Director of the Skeletal Biology and Engineering Research Center and of Prometheus, the Tissue Engineering Division of Leuven Research and Development; co-Director and Clinical Director of the Stem Cell Institute at the KU Leuven, Belgium.
Career Track: He obtained his MD, PhD degree and Board Certification in Rheumatology at the University of Ghent, Belgium in 1986. He spent his postdoctoral training at the National Institute of Dental Research, National Institutes of Health in Bethesda, USA between 1986 and 1991. He became subsequently group leader of the Developmental Biology Unit at the Bone Research Branch of the NIDR, NIH, Bethesda, MD, USA till 1997. In the fall of 1997, he accepted the position of Head of the Division of Rheumatology at the University Hospitals Leuven and became Professor at the KU Leuven.
Research expertise: Discovery of novel molecular players in both BMP and Wnt signalling pathways and their role in skeletal and joint biology and human arthritic diseases. Expertise in Regenerative Medicine and Tissue Engineering supported by contributions in the field of cellular therapeutics and adult stem cells for the regeneration of skeletal tissues. Clinical expertise mostly in the field of osteoarthritis and osteoporosis.
Some Senior International Achievements/Activities:
European Research Council: Advanced Grant holder 2012-2017
Permanent Member of the Interdisciplinary Expertpanel, Research Foundation Flanders
Member of steering committee of REMEDIC and QUANTISSUE, European Science Foundation
Founder, scientific and medical advisor of TiGeniX (Haasrode, BE).
Member of the board of directors of Pharmacell (Maastricht, NL).
(Photograph F.P.Luyten: SA Karott’ NV, Brussels)
Immunological Features of the development of RA over time
The Netherlands Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disease affecting primarily the joints. With more sophisticated and effective therapies becoming available, early intervention is crucial for preventing irreversible joint damage. Antibodies to citrullinated antigens (ACPA) provide an effective tool to diagnose erosive arthritis in a very early stage of the disease.
All strategies in RA clearly show that a window of opportunity exists during which the disease contracts characteristics that make the disease process chronic.
Analyses of the immune response has learned that the immune response against citrullinated antigens with respect to antigen specificity, isotype usage and affinity maturation occurs. Using a new autoantibody system, autoantibodies against carbamylated antigens shows that development of the autoimmune response in RA is probably not antigen specific. The focus of the current research is glycosylation differences between all autoantibodies and the detection of specific changes in antibodies against citrullinated antigens.
Biography of Prof Dr Tom W. J. Huizinga, born in 1960 in Amsterdam.
Prof Huizinga currently is chairman of Rheumatology at LeidenUniversityMedicalCenter, the oldest University of the Netherlands.
He received his MD from the University of Amsterdam at 1986, after which he joined the Army as a Bloodtransfusion specialist from 1986-1987. After that he received in 1999 his PhD cum laude on the biochemical and functional characterization of Fc-gamma Receptors. In 1990 he worked as a postdoc in Dartmouth Medical School, New Hampshire, USA. In 1991 he was ratified as an immunologist and started his training in internal medicine. He finished his rheumatology training in 1997.
From the period of 1994-1999 he received a fellowship of the Royal Academy of Arts and Sciences to study: “Regulation of TNFa-production in rheumatoid arthritis”. From 1998 he was appointed associate professor in rheumatology and since 2000 he was appointed as full professor.
In 2006 he became chairman of Rheumatology in Leiden.
Professor Huizinga received a number of prizes for his work among the “Boerhaave prize for outstanding contributions to Immunology” and the “Howard and Martha Holley Award: ACR-Southeast Regional Meeting “Cytokine polymorphisms in disease”.
He has served on a number of committee’s among which both the planning committee of the Annual Meeting Planning Committee of the American College of Rheumatology (2000-2003) and the planning committee of the Annual Meeting Planning Committee of the Eular (2004-2007).
He serves on the board of the Dutch Society of Rheumatology as well as on a number of editorial boards such as Genes and Immunity, International Journal of Advances in Rheumatology, Joint Bone Spine Revue du Rheumatism International Edition, Annals of Rheumatic Diseases, Plos Medicine and Current Rheumatology Reviews.
He has (co)authored over 500 peer-reviewed articles, his H-factor is 66 and has written over 10 book chapters.
Lupus Pathogenesis: B vs. DC and Other NET Results
“I will discuss the differential roles of B cells and myeloid cells in promoting T cell activation and disease in lupus. B cells have long been known to play a critical role in lupus, in large part by promoting activation of autoreactive T cells and possibly via pathogenic autoantibodies. Two questions have remained about B cells in lupus: 1) how are they activated in the first place; and (2) are they the primary antigen-presenting cells for autoreactive T cells, or do they merely amplify T cells that obligatorily have to be activated by DCs first? The answers to these questions have profound impacts on our concepts of how tolerance is actually broken in lupus and most likely other autoimmune diseases. I will present our data addressing both of these issues. This also raises the question of what non-redundant roles do DCs—and other myeloid cells—play in promoting or regulating lupus. We have been using genetic approaches to investigate the contributions of DCs, and several key molecules that DCs express, in the activation of T cells and in promoting target organ disease in lupus. Most recently we have used a genetic approach to investigate the role of neutrophil extracellular trap (NET) formation. I will present recent data from these studies.”
Development of New Therapeutics for Rheumatic Diseases
After receiving his medical degree from the New York University School of Medicine and completing residency training at the StrongMemorialHospital in Rochester, New York, Lipsky became a Clinical Associate at the National Institute of Allergy and Infectious Diseases, NIH in 1971. For the next four years, Lipsky received clinical training in rheumatology, allergy and infectious diseases and carried out research on the role of antigen presenting cells in initiating and regulating immune responses. In1975, Lipsky moved to the University of Texas Southwestern Medical Center at Dallas, initially as an Instructor in Internal Medicine and progressing to the rank of Professor of Internal Medicine and Microbiology in 1983. Later appointments at SouthwesternMedicalCenter included Director of the HaroldCSimmonsArthritisResearchCenter, Co-Director of the Immunology Graduate Program, and Director of the Rheumatic Disease Division of the Department of Internal Medicine. Lipsky was named the Harold C Simmons Professor in Arthritis Research in 1995. From 1999-2004, he served as the Director of the Intramural Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases and also as the founder and the Chief of the Autoimmunity Branch in NIAMS.
Delivering the Albrecht-Hasinger-Lecture 2011 at the German Rheumatism Research Center Berlin Dr. Peter E. Lipsky will talk about „Development of New Therapeutics for Rheumatic Diseases“:
“Despite recent advances in the treatment of rheumatic diseases, current therapy remains imperfect. Biologic agents are not available to all because of cost, and in those receiving these products, remissions are uncommon, adverse events are too frequent and loss of efficacy because of immunogenicity is a progressive problem. Deductive science aimed at identifying new targets of therapy has produced new candidate treatments that are in development. Another source of new therapies is the large numbers of herbal products that have been used for years in traditional medicine. One of these is an extract of the deciduous vine Tripterygium wilfordii Hook F(TwHF, thundergod vine, Lei gong teng), which has been used in traditional Chinese medicine for more than 500 years. Although clinical experience suggests efficacy in a number of inflammatory conditions, the mechanism of action of this material as well as its impact on specific diseases have not been well documented. A research program was, therefore, undertaken to: 1. Identify the mechanism of action of extracts of TwHF; 2. Determine the active components; 3. Standardize growth and extraction procedures; and 4. Confirm efficacy in rheumatoid arthritis by controlled clinical trials. Through a series of in vitro and in vivo experiments, the mechanism of action of extracts of TwHF was demonstrated to involve the inhibition of transcription of a number of pro-inflammatory genes by interference with the activity of the transcription factors AP-1, NFAT and NF-KB. Although the extract contained more than 300 components, its activity could be ascribed to a small group of diterpenoid triepoxides, of which triptolide and tripdiolide were the major contributors. Standardization of the extraction procedure using sequential ethanol and ethyl acetate as well as controlled cultivation of single cultivar plants yielded a highly reproducible extract. Finally, to document efficacy in rheumatoid arthritis, controlled trials comparing the extract to placebo as well as an active comparator demonstrated significant clinical benefit and protection against radiographic progression. Benefit paralleled a significant decline in IL-6 levels. The efficacy of extracts of TwHF suggests that this material might be a useful therapy for rheumatoid arthritis and other rheumatic diseases and definitive trials are planned to test this possibility.“
Ma J et al. Pytochemistry 2007; 68:1172-1178.
Schmidt BM et al. Nat Chem Biol 2007; 3:360-366.
Tao XL et al. Arthritis Rheum 2008; 58:1774-1783.
Goldbach-Mansky R et al. Ann Int Med 2009; 151:2290240.
Rheumatoid arthritis: from pathogenesis towards prevention of immune-mediated inflammatory disease
Professor Paul-Peter Tak is Professor of Medicine and Director of the Division of Clinical Immunology and Rheumatology at the Academic Medical Center (AMC)/University of Amsterdam in Amsterdam, the Netherlands, since 1999. He received his medical degree at the Free University (VU) Amsterdam and was trained as an internist and rheumatologist at Leiden University Medical Centre, where he also received his PhD degree. For seven years, he worked at UCSD (La Jolla, CA) – first as a visiting scientist, later as Clinical Associate Professor. From 2004 to 2008 he also served as Medical Director of the Dubai Bone and Joint Centre (Dubai, UAE). He founded in 2005 Arthrogen B.V., a company developing gene therapy, and has served as Chief Scientific Officer since then.
The recipient of numerous grants and honours, including a variety of fellowships and visiting professorships, Professor Tak is also a member of the EULAR (European League against Rheumatism) Scientific Committee and of the Annual Meeting Planning Committee of the ACR (AmericanCollege of Rheumatology). His extensive bibliography includes a list of more than 300 peer-reviewed clinical and basic research papers, as well as books on various aspects of immunology and rheumatology.
Professor Tak’s major research interests include signal transduction pathways, the pathogenesis of synovial inflammation in rheumatoid and psoriatic arthritis and the development and evaluation of immunotherapies and gene therapy for these conditions.
Delivering the Albrecht Hasinger Lecture 2010, Paul-Peter Tak will talk about “Rheumatoid arthritis: from pathogenesis towards prevention of immune-mediated inflammatory disease”:
“The etiology of rheumatoid arthritis (RA), a prototype immune-mediated inflammatory disorder, is poorly understood. Microarray analysis as well as immunohistologic examination of the inflamed synovial tissue of RA patients has provided evidence for a heterogeneous pathogenesis. It appears that different pathways may ultimately lead via a common final pathway to the clinical signs and symptoms associated with the syndrome called RA. Of interest, targeted therapies with a different mechanism of action may result in clinical improvement, in part due to a shared indirect effect on synovial macrophages.
The presence of anti-citrullinated protein antibodies (ACPAs) defines a distinct subgroup of RA patients, in which the interaction between the genetic background and environmental factors like smoking contributes to the risk of developing RA. Of note, rheumatoid factor and/or ACPA may be found in healthy individuals, years before the development of clinically manifest RA. The role of B cells in the pathogenesis of this RA subset is supported by the presence of B cells and plasma cells in the synovium and in particular by the beneficial effect of anti-CD20 antibody (rituximab therapy) treatment in autoantibody positive RA. The decrease in B lineage cells in the synovium between week 4 and 16 after initiation of rituximab treatment is related to the decrease in ACPA serum levels as well as clinical improvement after more prolonged follow up.
Systematic analysis of the synovium in different stages of RA has shown that so-called early RA represents chronic synovial inflammation. Subclinical inflammation of the synovium does not coincide with the appearance of serum rheumatoid factor or ACPA antibodies during the pre-RA stage. Thus, systemic autoimmunity precedes the development of synovitis, suggesting that a ‘second hit’ is involved. Data will be presented that support the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.”
The Immune System in Rheumatoid Arthritis – In Need for Rejuvenation
Weyand has just joined the faculty of Stanford University as a professor of medicine. She received her training in medicine and immunology in Germany and completed a fellowship in rheumatology at Stanford University. She was the Barbara Woodward Lips Professor of Medicine and Immunology at the Mayo Medical and Graduate School in Rochester and in 2004 became the David Lowance Professor of Medicine and the Director of the Lowance Center for Human Immunology and Rheumatology at Emory University School of Medicine.
Weyand has received numerous awards and honors including the Henry Christian Award for Excellence in Research (1991), the Henry Kunkel Young Investigator Award (1992), the Carol Nachmann Award for Rheumatology (1995), the Mayo Foundation Outstanding Investigator Award (1999), the Emory University Outstanding Research Citation Award (2006), and the Paul Klemperer Award (2006). She has been elected a member of the American Society of Clinical Investigation and the American Association of Physicians.
Professor Weyand’s principal area of research investigates mechanisms of disease in patients with chronic inflammatory syndromes, with a specific focus on rheumatoid arthritis and inflammatory blood vessel disease. Her primary objective has been to define molecular mechanisms of immune-mediated tissue damage, with the ultimate goal to reduce the burden of autoimmune disease and to develop diagnostic and therapeutic tools to improve immune function in patients and in healthy individuals.
Delivering the Albrecht Hasinger Lecture 2009, Cornelia Weyand will talk about “The Immune System in Rheumatoid Arthritis – In Need for Rejuvenation”:
“Rheumatoid arthritis (RA) is a prototypic autoimmune syndrome in which chronic joint inflammation causes pain, deformity and disability. Besides the joint destruction, RA is complicated by accelerated cardiovascular disease; significantly shortening life expectancy. RA patients have increased risk to develop lymphoma and are susceptible to infection, disease complications resistant to current anti-inflammatory therapy. The traditional dogma proposes that innate and adaptive immunity is hyperactive, promoting autoantibodies and formation of complex lymphoid structures in the inflamed joint. Persistence of arthritogenic antigen is assumed to sustain chronicity. Cytokines have been identified as critical amplifiers of inflammation and as valid targets for anti-inflammatory therapy.
Recent evidence suggests that beside antigen-induced T cell activation other pathways are critically involved in promoting tissue-destructive immunity. Specifically, by determining the survival and longevity of T cells, mechanisms of maintaining DNA integrity and repairing broken DNA strands have emerged as key regulators of the immune system. T cells with shortened and uncapped telomeres and fragmented DNA occupy the immune system in RA, suggesting mechanistic similarities between this autoimmune syndrome and the progeroid syndromes.
T cells are long-lived cells and the carrier of immune memory believed to mediate chronic inflammation. Unlike most other somatic cells, T cells can upregulate telomerase and elongate their telomeres to prolong survival. In RA telomeres are age-inappropriately eroded by 1500 kb. Telomeric loss affects not only memory T cells, but also unprimed naïve T cells and, as we have recently shown, CD34 bone marrow hematopoietic precursor cells. The underlying mechanism involves a defect in upregulating the telomere-elongating enzyme telomerase. Knock-down of telomerase activity in healthy T cells renders them susceptible to apoptosis. Repair of telomerase activity in RA T cells protects them from apoptotic death implicating this enzyme in cell fate decisions. Insufficiency to maintain intactness and stability of DNA is not limited to the telomeric ends of chromosomes but equally involves non-telomeric DNA strands. RA T cells are loaded with damaged DNA, mostly double strand breaks. Unless tackled by vigorous repair activity double stand breaks are lethal. Molecular analysis of the DNA repair machinery demonstrate that RA T cells are deficient for the DNA repair enzyme ataxia-telangiectasia-mutated (ATM) and essentially mimic abnormalities in patients with the inherited syndrome ataxia telangiectasia. Forced overexpresion of ATM in RA T cells restores DNA repair, improves radiosensitivity and protects cells from apoptotic death.
In essence, RA emerges as a syndrome of subtle chronic T cell loss, forcing the system to respond with excessive autoproliferation. This response pattern imposes chronic proliferative stress and premature immunosenecence. With nuclear instability emerging as an RA-associated mechanism, therapeutic approaches should be reconsidered and should include measures of immune rejuvenation.”
Professor Steffen Gay received his clinical training in Leipzig, Wuerzburg and Munich and then went on to the University of Alabama in Birmingham, USA, before becoming, in 1996, head of the Department of Rheumatology at the University Hospital of Zurich, one of the most renowned centers for experimental rheumatology in Europe.
In addition to his research, Professor Gay’s main focus is on promoting young medical scientists. Thanks to his efforts, the scientific centers in Alabama and Switzerland, where Gay works, have been designated so-called “WHO Collaborating Centers,“ which makes it possible for them to take part in international academic exchanges with countless universities – in particular exchanges of fellowships recipients and researchers in rheumatology.
In the Albrecht Hasinger Lecture 2008, Professor Gay will talk about “Epigenetics in Rheumatoid Arthritis“ and explain the latest findings of his research group on the molecular and cellular basis of joint destruction in rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. Special emphasis is given to the epigenetic mechanisms of gene regulation.
- 2007 Joachim Kalden – Erlangen, Deutschland
- 2006 Maxime Dougados – Paris, Frankreich
- 2005 Martin Weigert – Chicago, USA
- 2004 Lars Klareskog – Stockholm, Schweden
- 2003 Diane Mathis – Boston, USA
- 2002 Bevra Hahn – Los Angeles, USA
- 2001 Iain B. McInnes – Glasgow, Großbritannien
- 2000 Ferdinand C. Breedveld – Leiden, Niederlande
- 1999 Auli Toivanen & Paavo Toivanen – Turku, Finnland
- 1998 Nathan J. Zvaivler – San Diego, USA
- 1997 Derrick Brewerton – Westminster, Großbritannien
- 1996 Eng M. Tan – La Jolla, USA
- 1995 Frank A. Wollheim – Lund, Schweden
- 1994 Peter H. Schur – Boston, USA