Bone marrow glucose metabolism is linked to impaired immunity in inflammatory disease

• Applicant: Dr. Kian Marjani
• Subject Area: Endocrinology, Diabetology, Metabolism ; Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575059640

The bone marrow (BM), as the site of production for blood and immune cells (haematopoiesis), is central to the immune response. Quiescent haematopoietic stem cells typically meet their energy demands in the low-oxygen BM environment via anaerobic glycolysis. However, during acute stress, such as a ST-elevation myocardial infarction (STEMI), or during chronic inflammation, haematopoiesis is strongly activated to meet the increased demand for cells. Metabolic diseases such as type 2 diabetes (T2D) can disrupt these sensitive processes and negatively influence the immune response. Our own preliminary MRI studies have already demonstrated a reaction in the sternal BM following STEMI, measurable as increased T2 relaxation times. However, the underlying metabolic processes could not be non-invasively investigated to date, as common methods like MRI do not provide metabolic information, and PET-CT is associated with radiation exposure. This research project will therefore be the first to apply the innovative, radiation-free technique of deuterium magnetic resonance spectroscopy (²H-MRS) to investigate glucose metabolism in the human BM. The technique tracks the breakdown of orally administered, deuterium-labelled sugar into key metabolites such as lactate (anaerobic) and glutamine/glutamate (aerobic). While the technique is established in organs such as the brain and liver, its application in the BM represents a new technical challenge due to its heterogeneous composition. The project's objectives are clearly defined. Firstly, the ²H-MRS method will be technically established in the easily accessible femur of healthy participants, both at rest and after standardised physical exercise. Subsequently, the influence of age and chronic inflammatory diseases, such as rheumatoid arthritis and T2D, on BM metabolism will be investigated. Finally, the technique will be transferred to the sternum. The goal here is to characterise its metabolic activation after a myocardial infarction and to explore a potential direct communication axis between the sternum and the heart (a "sterno-cardiac axis"). The project aims to provide fundamental insights into the complex interplay between metabolism, the immune system, and cardiovascular diseases. The non-invasive visualisation of BM energy metabolism could enable better risk stratification for patients and create the basis for new, targeted therapeutic approaches.

• DFG Programme: WBP Fellowship
• International Connection: Austria
• Host: Professor Martin Krssak, Ph.D.