Our research group investigates the role of adult stem and progenitor cells in the hypothalamic-pituitary-adrenal (HPA) axis, with a particular focus on the adrenal gland and its capacity to adapt to physiological, psychological and metabolic stress. We aim to understand how stress and metabolic signals regulate adrenal plasticity, tissue regeneration and steroid hormone production, and how dysregulation of these processes contributes to disease.
A major focus of our research is understanding how the adrenal gland adapts to different forms of stress. We investigate how acute and chronic stress influence adrenal tissue remodeling, progenitor-cell activation, cellular differentiation and steroidogenesis. We are particularly interested in the mechanisms that determine whether stress induces adaptive or maladaptive changes in adrenal function.
An important emerging aspect of our work is sexual dimorphism in the stress response and adrenal adaptation. We have observed marked differences between females and males in adrenal tissue turnover and cellular responses to stress, suggesting that the mechanisms underlying adrenal adaptation are strongly influenced by sex. We are investigating the molecular and cellular basis of these differences and how sex-specific responses to stress may contribute to differences in susceptibility to stress-related and metabolic diseases.
An imbalance of the stress response is strongly associated with a wide range of diseases, including mental disorders such as depression, anxiety and burnout, as well as metabolic and inflammatory disorders. We hypothesize that repeated or early-life exposure to stress may induce persistent molecular and epigenetic changes in HPA-axis stem and progenitor cells, thereby altering their response to subsequent stress and increasing susceptibility to disease later in life. To investigate these mechanisms, we use experimental stress models and combine molecular, cellular and multi-omics approaches, including RT-qPCR, transcriptomics, single-cell RNA sequencing, proteomics, lipidomics and epigenetic profiling.
A particular focus of our research is the interaction between stress and metabolism. We investigate how metabolic signals and metabolic diseases influence adrenal function and tissue remodeling. Using high-fat-diet models and in vitro adrenal systems, including primary adrenal spheroids, we study how factors such as insulin, adipokines and altered lipid metabolism affect adrenal progenitor-cell activity, mitochondrial function and steroidogenesis. These studies aim to elucidate how metabolic dysfunction alters the capacity of the adrenal gland to adapt to stress and whether these effects differ between females and males.
We have also established in vitro systems to study adrenal progenitor cells and their differentiation into steroid-producing cells. Using three-dimensional adrenal spheroids and stem/progenitor-cell differentiation models, we investigate the cellular and molecular mechanisms underlying adrenal regeneration and steroidogenic differentiation. In the long term, this work may contribute to the development of regenerative approaches for the treatment of adrenal insufficiency and other disorders of adrenal function.
A further research direction of the laboratory investigates the effects of environmental stressors and the human exposome on health and disease. In collaboration with clinical groups, we study the presence and potential biological consequences of environmental contaminants, including microplastics, nanoplastics and per- and polyfluoroalkyl substances (PFAS).
In particular, we investigate whether therapeutic apheresis can alter the circulating exposome and remove or redistribute environmental contaminants. Our recent studies have demonstrated reductions in several PFAS and microplastic-associated signals following apheresis and have raised the possibility that environmental contaminants may interact with lipoproteins and plasma proteins or be mobilized from tissue compartments. We are now investigating the biological relevance of these findings and their potential links to metabolic, inflammatory and neurodegenerative diseases.
Together, these projects are united by a common research theme: how stress, metabolism, sex and environmental exposures interact to influence stem-cell function, tissue adaptation and disease susceptibility. By combining experimental models, advanced cellular and molecular techniques, multi-omics approaches and translational studies in human samples, our long-term goal is to identify mechanisms that can be targeted for the prevention and treatment of stress-related, metabolic and endocrine diseases.