Current Title and Department: Dr. rer. nat.; post-doctoral position at the Institute of Orthopaedic Research and Biomechanics, Ulm university medical center
Current Employer: Ulm University Medical Center
Undergraduate Degree, University: Ulm University
Graduate Degree, University: Ulm University
Post-doctoral Position: Institute of Orthopaedic Research and Biomechanics
Who have been your mentors? Melanie Haffner-Luntzer and Anita Ignatius
What led you to study the effects of the immune system on bone healing? What was your first project on osteoimmunology?
Bone biology fascinated me during my bachelor studies. Because of this, when it was time for me to look for my PhD project, I searched for a bone biology related project. My PhD project was my first on the subject of osteoimmunology and while performing it, my interest in osteoimmunology arose. In this project, we investigated the role of catecholamines in fracture healing. More specifically, the role of catecholamines produced by myeloid cells, as opposed to systemic catecholamines produced in the adrenal gland, and the subsequent effects of chronic psychosocial stress on bone homeostasis and fracture healing (Kuhn MR et al. Front Endocrinol (Lausanne). 2022 Sep 15;13:997745. doi: 10.3389/fendo.2022.997745. PMID: 36187089; PMCID: PMC9520980).
What has been your most unexpected result when studying the immune response in bone healing?
The most unexpected result was how important the role of catecholamines produced by immune cells is for the inflammatory process and also for fracture healing. This was a surprise given that the adrenal gland is the major source for systemic catecholamines. Furthermore, we discovered that the effects of chronic psychosocial stress on fracture healing critically depend on neutrophil-derived catecholamines (Tschaffon-Müller et al. Nat Commun. 2023 Jun 5;14(1):3262. doi: 10.1038/s41467-023-38616-0. PMID: 37277336; PMCID: PMC10241819).
What are your current interests in the field of osteoimmunology?
My current projects are indirectly related to osteoimmunology. I am very interested in how other factors, such as estrogen or the gut microbiome can have effects on bone homeostasis or fracture healing via the immune system.
What advantages and challenges are associated with studying osteoimmunology in your research model?
In our study, we worked with a mouse model with a cell-specific knockout of tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, using the Cre-LoxP system. That way, it was very simple to study the role of catecholamines produced by myeloid cells in bone. Other advantages of our knockout mouse model were that we could quickly get results analyzing immune cell populations by FACS, and that we could easily isolate specific immune cell types from the bone marrow of mice by MACS separation. The biggest challenge of our study was trying to measure catecholamines produced by immune cells. This proved to be more challenging than originally anticipated. We also performed a clinical approach with fracture patients, however, here we could only do a correlational analysis of the expression of tyrosine hydroxylase in the fracture hematoma with mental stress scores and self-reported healing progress. I would expect a deeper study of the stress effects on bone homeostasis and fracture healing in humans to be very challenging as well.
Is there a specific barrier that once addressed might expand clinical translation of osteoimmunology research?
One barrier, which should be addressed, is that we should look at the organism as a whole system instead of focusing on one pathway or cell-to-cell interaction, especially if you are working under standardized conditions, how it is usually performed with laboratory animals. There are many comorbidities which can influence the immune system and thereby influence its effects on bone. For example, in our project, chronic psychosocial stress turned out to have a great effect on the immune system which significantly affected both bone homeostasis and fracture healing.
What advice would you give investigators who want to include osteoimmunology into their research program? What learning resources or techniques would you recommend?
One special advice would be to not only focus on the influence of immune cells on bone cells but also vice versa, to investigate the influence of bone cells on immune cells. Not much is known about this so far, and I believe this to be important. Regardless of what techniques you decide to use for analysis, I recommend to always collaborate with other groups. Collaborations are crucial to proper interpretation and analysis of results when venturing into a new field.
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