Rare diseases affect children and adolescents in eight out of ten cases. Their participation in medical progress therefore depends crucially on dedicated pediatricians who are committed to the balancing act between bedside and laboratory. The Alliance4Rare research network initiated by the Eva Luise and Horst Köhler Foundation provides structured Clinician and Medical Scientist Programs (CS4RARE) to prepare researching paediatricians for this challenging task and to give them the necessary freedom for scientific work at a high level. The programs grant participants protected research periods in which they are released from clinical duties to advance scientific projects on rare diseases.
Dear Dr. Körholz, you have been chosen for the Alliance4Rare Clinician Scientist Program. What was your motivation to pursue this particular path in science and the clinic?
Already during my practical year, I was fascinated by the versatility of paediatrics, especially the numerous rare diseases that one encounters in a university hospital. I therefore began my further training in paediatrics at the Centre for Rare Diseases and in paediatric immunology. In the latter, I was particularly impressed by the combination of clinical work and basic research: the so-called ‘bedside-to-bench’ principle. The indispensable detailed medical history and clinical examination, as well as individual functional laboratory analyses and, last but not least, genetic diagnostics help to better understand ‘gaps’ in the immune system of patients. Ultimately, the malfunction of individual proteins involved in the immune system also provides a better understanding of their function in healthy people.
Close collaboration between the laboratory and clinic is particularly crucial in immunology. It makes it possible to customise functional tests to the ‘gaps’ in our patients’ immune systems and thus open up ways to targeted therapeutic strategies. I wanted not only to understand immunological research, but also to actively apply it myself in order to develop innovative diagnostic and therapeutic approaches.
What are you currently working on and what would you like to achieve in the field of rare diseases?
The spectrum of my immunological research is very diverse. It ranges from analysing prenatal influences on thymus maturation to collaboration in various European registries and drug trials (orphan drugs) to detailed investigation of specific monogenetic immunodeficiencies. The focus of my work is currently on the further characterisation of SOCS1 insufficiency. This is a monogenetic immunodeficiency that primarily manifests itself through immune dysregulation and can appear, for example, as systemic lupus erythematosus (SLE).The SOCS1 protein plays a central role in numerous intracellular signalling pathways. A defect in this protein can therefore not only cause a variety of dysregulations of the immune system, but also offers numerous starting points for targeted therapeutic interventions. SOCS1 insufficiency is an autosomal dominant immunodeficiency with variable penetrance that is probably often underdiagnosed. Affected individuals are likely to be found in different specialities such as dermatology, rheumatology or gastroenterology. My aim is to raise awareness of congenital immunodeficiencies in patients with immune dysregulation. At the same time, I am keen to analyse individual clinical pictures and processes in order to develop customised treatment strategies. In the long term, these findings could also be transferred to other immunological processes, such as the development of cancer.
Our patients are not only recipients of medical care, but also valuable teachers. We learn from them in order to actively shape the medicine of tomorrow.
What opportunities does the funding from Alliance4Rare open up for you in your day-to-day work that you wouldn’t otherwise have?
The funding gives me 50 per cent time off, which I will use in a variety of ways. On the one hand, it enables me to advance my laboratory research in parallel with my clinical work. On the other hand, I plan to use the time cumulatively for a research stay in a renowned immunology laboratory in the USA (NIH). This interdisciplinary and intercontinental exchange will enable me to learn new laboratory methods and techniques that are essential for researching previously poorly understood components of the immune system. At the same time, the stay offers me the opportunity to significantly advance my own research project.
In addition, the collaboration with the Alliance for Rare opens up important networking opportunities. The exchange with other clinician scientists across institutional boundaries is not only inspiring, but also a central building block for progress in research into rare diseases.
Dr Julia Körholz comes from Düsseldorf and grew up in Leipzig. She studied human medicine at the Albert-Ludwigs-University Freiburg and the Technical University Dresden. As part of an experimental doctoral thesis at the Centre for Regenerative Therapies Dresden, she investigated how and why individuals react differently to positive changes in their environment. Since 2019, Dr Julia Körholz has dedicated herself to clinical and scientific work in paediatric immunology as a doctor in training at the Clinic and Polyclinic for Paediatric and Adolescent Medicine at Dresden University Hospital. In 2024, she took on the role of Anchor Clinician Scientist of the Alliance4Rare at the UK Dresden.
