On August 30 2022, the Executive Board of the University of Amsterdam decided to appoint Dr. S.W. (Sander) Tas as Professor of Rheumatology, in particular the molecular basis and treatment of autoimmune diseases. Dr. Tas will openly accept his professorship by delivering his inaugural lecture on Thursday, June 15, 2023, at 4:30 p.m. Given his appointment, we interviewed Sander about his field of research, most profound outcomes in his career and the importance of personalized treatment strategies in autoimmune disorders.
Dr. Tas is a translational scientist with experience in both basic and clinical translational research. He has an H-index of 32 (the H-index is an author-level metric that measures both the productivity and citation impact of publications), and has written>100 scientific articles. His translationalresearchhas a strong focus on themolecular regulation of inflammation and includes basic research on signal transduction, studies inpreclinical models of chronic inflammatory diseases, and state-of-the-art tissue analysis.
Dr. Sander Tas is Amsterdam UMC Principal Investigator since 2016, Program Leader "Inflammatory Diseases" of the Amsterdam Institute for Infection and Immunity (AMC/VUmc), board member of the Amsterdam Rheumatology and immunology Center (ARC), and member of the EULAR Research Committee. Since 2020 he is vice chair of the department of Rheumatology and Clinical Immunology at Amsterdam UMC. Furthermore, Sander is married and has 3 children. They live in the countryside near the city of Weesp (a short bike-ride from location AMC) where they recently built a sustainable house. He enjoys being outdoors, spending time with family and friends, and exploring the world.
The two sides of the immune system
On August 30 Dr. Sander Tas was appointed Professor of Rheumatology. His interest in autoimmune diseases stems primarily from the two-pronged nature of the immune system: ‘I am fascinated by the exceptional versatility of the immune system, which is crucial for pathogen control and prevention of cancer development. But despite multiple central and peripheral checkpoints to prevent unwanted immune responses to self-antigens, autoimmunity occurs and this can cause devastating inflammatory diseases that ultimately lead to tissue destruction and disability in patients.’ The pathophysiology of autoimmune diseases is what Sander wants to address with his research. ‘I want to increase our understanding of the immune system and develop novel strategies to prevent disease through early identification and reversal of autoimmunity or even strive towards a complete reset of the autoimmune response to improve the lives of our patients.’
Targeted therapies and more personalized treatment strategies
According to Sander, research into the molecular basis and treatment of autoimmune diseases is important because, while tremendous progress has been made over the past 20 years in developing new treatments for patients with chronic inflammatory diseases, treatment in individual patients has remained largely empirical. Most of the time a trial-and-error approach is used, often resulting in delayed treatment responses and potentially unnecessary side effects.
‘Of note, some of our patients do not respond at all to currently available treatments. Therefore, the development of new targeted therapies and more personalized treatment strategies is needed. To accomplish this, we need to increase our understanding of the immunological mechanisms underlying chronic inflammation, to identify new therapeutic targets that are “drugable” (i.e. via small molecule inhibitors). In addition, strategy trials can teach us which patients respond best to a particular treatment and provide biomarkers to predict treatment response.’
Bridge the gap between laboratory research and clinical care
According to Sander, many scientists are interested in the molecular basis of autoimmune diseases. But, not many clinicians are actually performing translational research to convert discoveries into clinical practice. This is a critical step that should receive more attention.
‘I think it is crucial when looking at the molecular basis and treatment of autoimmune diseases to bridge the gap between laboratory research and clinical care. Every patient has the potential to teach us something unique about their disease. At Amsterdam UMC, we are in a very good position to conduct this type of research, because we have extensive experience in examining unique patient samples such as lymph node biopsies and synovial tissue biopsies in combination with access to key technologies like (single cell)RNA sequencing and spatial transcriptomics.’
Decide Together
On the importance of a personalized approach in the treatment of rheumatoid arthritis, Dr. Tas says that for him the most important thing is to decide together with the patient on the best treatment option.
‘I strongly advocate the “Decide Together” campaign, as it is very important to discuss all the ins and outs of treatment with a patient to make sure you’re on the same page. This conversation gives you a chance to waive certain preconceptions and increase adherence to treatment. Moreover, we usually also take into account certain patient characteristics when choosing the best treatment for that particular patient. Nevertheless, most treatments are started empirically without first determining a molecular fingerprint of the pathological process in the individual patient, as is common in oncology. Currently, the first attempts are being made to implement this method in chronic inflammatory diseases as well, and I believe this is the way forward.’
Groundbreaking discoveries
In his career to date, Sander and his research groups have made two discoveries that are groundbreaking. First, the importance of a protein called NIK in angiogenesis (i.e. blood vessel growth), a process that contributes to many pathological conditions, including inflammatory diseases and tumor growth. ‘I will never forget the comment of one of our technicians when she performed an immunohistochemical staining of NIK on inflamed synovial tissue of patients with rheumatoid arthritis: “It looks very strange, the staining pattern resembles little circles”. These turned out to be blood vessels and further studies revealed that the NIK protein is only present in blood vessels in pathological conditions, not in healthy tissues. This allows targeting of NIK as this will not interfere with normal blood vessel growth. Experiments in several preclinical models indicate that this is probably more safe and effective than targeting of general factors that promote angiogenesis’.
Another key discovery evolves around the various cell types that are at play in an inflammatory response. Certain cells facilitate inflammation, whereas others reduce or contain inflammation. Sander’s team discovered the presence of cells expressing the transcription factor Autoimmune Regulator (AIRE) outside of the thymus in chronically inflamed tissues. These extrathymic AIRE expressing cells (eTACs) are for instance present in the inflamed synovial tissue of patients with rheumatoid arthritis and the inflamed salivary glands of patients with primary Sjögren’s syndrome, and the regulation of AIRE in these cells occurs via non-canonical NF-κB signaling. eTACs are likely to play an accessory role in ensuring or reinforcing peripheral tolerance and their function may be boosted to regulate inflammatory responses. The eTACs were unknown until recently and could potentially have a major impact on reducing inflammatory responses due to the molecules expressed by the AIRE cells. This is a novel approach to treat autoimmune diseases which is currently under further investigation.
Discover the autoantigen(s)
‘Within the field of autoimmune diseases the autoantigen(s) to which B and T cells respond are often not known, making it very difficult to design antigen-specific tolerogenic therapies to reset the immune system and ultimately establish a cure for these diseases.’ According to Sander the most important question yet to be answered is determining the autoantigen(s) that are involved in these diseases, as that may provide important clues to develop the optimal tolerogenic approach to ultimately also establish a cure for autoimmune diseases.
The RUBRIC project
Sander is also socially involved and contributes to several projects linked to prescription medicines: he is chairman of the Medicine Committee of the Dutch Society for Rheumatology, and participates in the national Horizon Scan Committee and the Medicine Advisory Committee of the Federation of Medical Specialists (FMS).
However, the biggest clinical challenge Sander faces in his field is performing precision medicine in patients with rare immune-mediated inflammatory diseases, as reimbursement issues are sometimes a big obstacle. However, Sander is a man who thinks in solutions rather than difficulties. That is why he initiated the RUBRIC project.
‘The RUBRIC project is aimed at rational use of biologics and targeted synthetic DMARDs in patients with rare immune-mediated inflammatory diseases and evaluation of efficacy and safety. This is important, because it is difficult to conduct randomized clinical trials in these rare diseases to demonstrate efficacy. The results generated in RUBRIC may ultimately help facilitate reimbursement for these therapies in rare inflammatory diseases.’
Persevere and pursue your goals
When Dr. Tas is asked what his advice would be for young researchers who aspire to become an established clinician-scientist, he states: ‘I would advise you to be original and always pay attention to unexpected results because they can be the most interesting. This is most likely to happen at the intersection of different areas of research. And if you have a good idea: believe in it and do not be put off if a grant application does not work out at the first instance, but persevere and pursue your goals!
Text: Esmée Vesseur