Infection & Inflammation

Our group focuses on diseases caused or maintained by alterations of the immune system, attempting to better understand their underlying mechanism to unlock new diagnosis and therapy monitoring strategies using in vivo models and advanced molecular imaging techniques such as combined positron emission tomography and magnetic resonance imaging. More specifically, we currently have 2 main areas of active research.

Inflammation:

The dysregulation of inflammation is a major source of concern in developed countries as, combined with a general aging of the population, the prevalence of chronic inflammatory diseases is rising. One of the major aspects of this dysregulation is the invasion of affected tissue by extracellular matrix fibers (ECM), termed fibrosis, resulting in a critical loss of function of the affected tissue. We have developed novel multimodal (PET/CT/MRI) imaging strategies to monitor the appearance and progression of fibrotic tissue in several diseases, from arthritis¹ to lung fibrosis² based on PET imaging of radiolabeled fusion proteins targeting the ECM. Our molecular imaging approach relies on the combination of PET molecular imaging, reporting specifically on fibrosis and an anatomical imaging pillar to not only precisely locate the affected tissues but act as a gold standard for the pathologies investigated. Furthermore, we have identified cellular senescence as a main driving force behind fibrotic progression, and are now focusing on investigating how imaging the senescent cell population during inflammation can predict the appearance of fibrotic tissue using novel PET senescence radiotracers. This is now performed in house and within the Cellular Senescence Network, a NIH-funded initiative. We hope that the outcome of this research will be used for risk-based stratification of patients with chronic inflammatory diseases in the clinics, in order to provide them with adequate therapy as early as possible.

Infection:

It is now recognized that bacterial and fungal infectious diseases constitute the main threat to public health in the 21^st century, notably due to the rise of antimicrobial resistance. In this landscape, early and accurate diagnosis of the microorganisms responsible for the infection can enable early therapy, as well as precise treatment monitoring, which are paramount to treatment success. This requires the development of novel, non-invasive, imaging tools.

One of the focus of our group is Aspergillosis, an invasive fungal disease recently highlighted by the WHO as one of the most threatening fungal pathogens. Through a long-term international research collaboration spear-headed by the WSIC, we have provided a completely novel aspergillosis imaging tool based on PET imaging of specific radiolabeled antibodies using a MRI PET-insert, yielding impressive results in a preclinical model of the disease^3-5. This effort recently led to the clinical translation of the approach with promising first results⁶, constituting the first specific in vivo imaging of the disease in patients. Optimization of the method through a DFG funded project is currently in progress.

A second focus is bacterial infection, notably how manipulation of the microbiome can alter the progression and eventually resolve infections of the gastro intestinal tract. Our approach relies on in vitro metabolic labeling of bacteria to enable in vivo click-chemistry radiolabeling, enabling in turn species-specific PET imaging of bacterial distribution. By following distribution of the virulent bacteria and specific commensals using these click-chemistry based PET imaging approach combined with anatomical CT/MRI of tissue, we expect a better understanding of the protective properties of the microbiome against infections. This research is fully embedded in and funded by the Cluster of Excellence EXC2124 “Controlling Microbiome to Fight Infections” and represents a completely new research avenue at the WSIC.

1. Beziere, N. et al. Theranostics 9, 2868-2881, (2019).
2. Isser, S. et al. J Nucl Med, jnumed.122.264552, (2023).
3. Rolle, A. M. et al. Proc Natl Acad Sci U S A 113, E1026-1033, (2016).
4. Davies, G. et al. Theranostics 7, 3398-3414, (2017).
5. Henneberg, S. et al. Nat Commun 12, 1707, (2021).
6. Schwenck, J. et al. J Nucl Med, jnumed.121.263251, (2022).