Projects

Traditional diagnostic and research methods in dermatology rely on serum samples and histomorphometric analyses of punch biopsies, effective for cell and molecule identification but inadequate for soluble factors like cytokines, often undetectable in serum. This may lead to overlooking their significance in disease mechanisms and the search for therapeutic targets and biomarkers.

The interstitial fluid (ISF) in skin contains high concentrations of these mediators, making it a valuable information source. Researchers, in collaboration with industry partners, are developing an innovative approach for ISF extraction and analysis using hollow microneedle (MN) patches on monocrystalline silicon-based chips (10x10 mm2). This method offers several advantages, such as minimally invasive sampling within 20 minutes, no need for expensive equipment or specialized personnel, and no detectable inflammation. This could significantly enhance the discovery of biomarkers and therapeutic targets in dermatology.

Inflammasomes are cytosolic multiprotein complexes that regulate the activity of cytokines IL-1β and IL-18. Among them, NLRP3 is the most extensively characterized. Uncontrolled activation of inflammasomes, particularly NLRP3, contributes to abnormal cytokine-dependent inflammation in rare genetic autoinflammatory diseases and common inflammatory conditions like diabetes, asthma, neurodegenerative disorders, cardiovascular, and skin diseases. Current treatments primarily involve blocking downstream cytokines or using immunomodulatory drugs, often with limited efficacy and side effects. Specific NLRP3 inhibitors could significantly enhance therapeutic outcomes. Currently, no NLRP3 inhibitors are approved for clinical use. Our project aims to identify and validate highly specific low-molecular-weight Inflammasome inhibitors for the treatment of NLRP3-associated diseases.

Chronic immune disorders like autoimmune diseases and allergies pose medical challenges. Current therapies are often nonspecific with severe side effects. The project aims to develop more targeted and effective compounds to address underlying immune issues.

This project involves the 1. identification, 2. validation and 3. target identification/validation of compounds to better control excessive chronic immune reactions. New compounds will be developed using in vitro assays and human immune cells to selectively suppress or stimulate immune mechanisms. The goal is to restore and sustain the immunological balance in chronic immune diseases by selectively modulating immune mechanisms, including regulatory T-cells. The compounds developed in this study aim to pave the way for novel therapies for chronic immune disorders. Preclinical investigations suggest sustainable treatment options that can alleviate symptoms and enhance the quality of life for patients.

In chronic allergies, mast cells and eosinophils engage in bidirectional interactions leading to cell activation. This interaction, known as the Allergic Effector Unit (AEU), is critical in chronic inflammation. This project aims to better understand AEU by blocking mediators and receptors to characterize pathways. Based on these insights, targeted therapeutic approaches are to be developed.

Within these projects, the effects of mast cell depletion in the human body are characterized. Patients who have received such a therapy document in detail possible positive or negative influences on general biological processes, are examined for changes in taste, hair growth or wound healing, and tissue samples from skin and mucosa are obtained and examined immunohistologically. Through these comprehensive studies, we expect not only to better understand the role of mast cells in the human body, but also to identify potential diseases that could benefit from such therapy in the future.

Patient reported outcome measures, or PROMs, have become an important component of patient care and clinical research. However, there are still numerous diseases where no suitable PROM exist. Currently, we are developing PROMs especially for chronic inducible urticaria such as cold urticaria or symptomatic dermographism to determine disease activity and severity and to assess disease-specific quality of life.

We maintain a biobank for all diseases seen in our specialty clinics, which allows us to correlate clinical parameters such as disease activity or quality of life impairment with specific blood values. Currently, this is being done for patients with chronic pruritus, where the clinical classification of itch is compared with laboratory values in order to facilitate future diagnosis of these patients and to enable them to receive targeted and effective therapy more quickly.