What is your personal vision of the direction of your field of research? In other words, why is it relevant and what are your main long-term goals?

The particular enrichment of mucosal-associated invariant T (MAIT) cells within the liver is very intriguing, yet the role of these cells in health and disease remains to be fully clarified. Based mostly on murine models, roles of MAIT cells in tissue repair and liver inflammation/fibrogenesis have been suggested, however, little is known about their function in the human liver, which is why my lab is focusing on analyzing patient-derived tissues. We are particularly interested in studying the interaction of MAIT cells with other cell types specific to the liver environment, e.g. hepatocytes and hepatic stellate cells (the latter being important drivers of liver fibrosis). Also, little is known about the influence of the gut microbiome on MAIT cell function, both in the gut and liver. Given that MAIT cells are activated by bacteria-derived metabolites, this connection holds particular relevance and is the primary focus of our ongoing projects. Our goal is to bridge the gap in understanding the role of MAIT cells within the immunological gut-liver axis and to generate results of potential translational value. Detailed knowledge on MAIT cell function in liver health and disease may impact future development of new treatment modalities for fibrotic liver diseases.

Thinking about this vision, what are your main contributions to the field?

Thanks to numerous fruitful clinical and scientific collaborations, as well as my experience as clinical hepatologist, we were able to analyze MAIT cells in patient-derived samples. It should be emphasized that human tissue is very precious when available for laboratory studies. Through our research, we demonstrated that hepatocytes, along with other liver cell types, are able to present bacteria-derived metabolites, thus acting as strong drivers of MAIT cell activation within the liver environment. Furthermore, we found that impaired intestinal barrier integrity leads to elevated exposure of the liver to MAIT cell-stimulatory bacterial metabolites. We thus hypothesize that conditions associated with a leaky gut – and hence resulting in higher levels of MAIT cell stimulatory antigens reaching the liver – cause increased MAIT cell activation and fibrogenic cues. This, in turn, could contribute to the pathogenesis of human inflammatory liver diseases. My further hypothesis is that MAIT cells, due to their proximity and interaction with hepatocytes, play a relevant role in liver tissue homeostasis.

What are the main challenges in your field of research?

I am particularly interested in liver diseases that are connected to the gut-liver axis. The growing incidence of the metabolic syndrome, because of the obesity epidemic, and the associated steatotic liver disease are becoming a significant global health threat. Understanding the involvement of immune cells in this disease, which is closely tied to changes in the gut microbiome, is of major interest.

The access to an adequate amount of human tissue derived from well-characterized patients is a challenging aspect of our research. The patient population is often heterogeneous, representing various stages of the disease, and is exposed to numerous influencing variables, including medications and different diets. Hence, a large number of patient-derived samples are required to draw the relevant conclusions.

Additionally, the purification of specific cell populations of interest from the liver tissue presents another obstacle. Many primary cells are short-lived and difficult to maintain in culture even for a short period of time.

What part of your work as a group leader do you enjoy/appreciate the most? If you can give an example… 

I very much enjoy brainstorming with my lab members and seeing the projects evolve. My foremost goal is to provide an integer and promotive work environment and also offer the basis for a future scientific career to the lab members who are aspiring to future independent academic careers. I’m also very happy to be able to offer a first insight into basic research for medical students, as I believe that already at this stage of their career, this can be decisive to spark their interest in biomedical research.

Last but not least? If we could grant you a scientific “wish”, apart from enough resources to perform your research, what would that be? The sky is the limit.. (This can be about research and science in general or specifically about your own work or field)

Success in contributing to finding a potent antifibrotic therapy, which will allow to help millions of patients worldwide. Myriads of scientists have provided insight into the pathogenesis of liver fibrosis, the pipelines of small and large pharma companies are full, let’s hope that there will be a breakthrough soon.

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