(1) Development of next generation therapies for inflammatory and genetic diseases of human epithelia

Aiming for new treatment options for severe, monogenic and inflammatory diseases, my lab has explored various approaches to deliver biomacromolecules such as proteins as well as small anti-inflammatory drugs to human epithelia. To allow for an efficient and targeted intraepidermal transport as well as drug delivery to mucus-covered epithelia like in the lung, smart drug delivery systems are required. Over the past 6 years, we provided the proof of concept that topical protein delivery is a feasible approach for the treatment of severe monogenic skin diseases and common inflammatory skin diseases like atopic dermatitis and psoriasis. Here, my group has investigated and compared the efficiency of various delivery systems ranging from polyglycerol-based nanocarriers to lipidic nanocarriers and microneedles aiming for novel treatment options which are urgently needed. In addition, about 4 years ago, we started investigating new approaches for efficient drug delivery to the bronchial epithelium and the intestine. Here, mucus-penetrating delivery systems are required for efficient delivery to the epithelium. Just recently, we started exploring the potential of an in situ gene correction approach for monogenic skin diseases. Here, CRISPR-Cas9 components are topically delivered into viable layers of the human skin using non-viral gene delivery. Moreover, my lab is interested in unraveling the interactions of nanocarrier systems with their guest molecules, loading processes and interactions between the delivery system and the target structure. For those studies several techniques are applied including ATR-FTIR, scanning electron microscopy, EPR spectroscopy or fluorescence life time imaging. Additionally, the biocompatibility and nanotoxicological aspects are of interest to us. Here, cytotoxicity, activation of immune cells or irritative properties of nanoparticles and biomacromolecules attaching to their surface (= protein corona formation) are investigated.

(2) Reconstructed human tissues and disease models
Animal models are considered the gold standard for basic and preclinical research. However, increasing criticism evolved from scientific and ethical concerns. More than 90 percent of potential therapeutics fail in clinical trials despite promising results in preclinical studies. Reasons for that include poor characterization of animal models, a lack of sufficient quality within in vivo studies but also, and maybe most importantly, distinct inter-species related differences between animal models and humans. Hence, my lab is developing human-based organ (disease) models which can be used for preclinical drug testing, biopharmaceutical studies as well as fundamental research on (patho)physiological aspects. Currently, my lab is focusing in the development of human-based (disease) models of human skin and lung tissue. Over the past years, my lab has established and characterized skin models which closely emulate characteristics of inflammatory skin diseases. We have successfully used these models for drug testing, the evaluation of new drug delivery systems as well as for unraveling pathomechanism. We also succeeded in the implementation of critical immune cells such as T cells which is an important step when aiming for valid and predictive preclinical models which facilitate the translation from bench-to-bedside. These models are now being used to study the efficacy and tolerability of new anti-inflammatory compounds or topical formulations such as nanocarriers. Other projects focus on the development of an in vitro model of the bronchial epithelium. The bronchial epithelial models are currently used for infection studies with influenza viruses aiming to explore new anti-viral strategies. About 2 years ago, my lab has started to co-cultivate organ models, whereas we established dynamic setups to co-cultivate skin and lung models. This is of particular interest with regard to atopic diseases and the atopic march. Our aim is to provide a more detailed understanding of this intertissue communication and on a long term perspective, to establish multi-organ cultures aiming for human-on-a-chip approaches for drug testing.

(3) Regenerative approaches for the treatment of fibrotic diseases & promotion of wound healing

Fibrosis is the cause of various diseases in the human body and occurs in a variety of organs (e.g. heart, lungs or skin). Effective therapeutic or preventive measures are mainly lacking so far. New findings from plastic surgery show, however, that autologous fat injections, e.g. in women that underwent mastectomy, have an substantial improvement of phenotype and functionality of hypertrophic scar tissue . The underlying mechanisms are still unknown. We are therefore interested in the communication between connective and adipose tissue. First results show, that adipocytes exert strong regenerative effects on myofibroblasts and induce their de-differentiation. The de-differentiation is dependent on BMP-4 and the activation of the of PPARgamma receptors. This is particularly noteworthy since myofibroblasts have been considered finally differentiated cells.