Multiple Sclerosis (MS) is a chronic inflammatory disease of the CNS, which is characterized by massive T cell and macrophage infiltration leading to demyelination, axonal damage and neurological symptoms such as paralysis. Experimental autoimmune encephalomyelitis (EAE) is an animal model that mimicks many aspects of the pathogenesis of MS and thus can be used to study disease mechanisms and new treatment approaches in preclinical models. In cooperation with colleagues from the clinic, we also study blood samples collected from MS patients. Our research aims to better understand the role of steroid hormone receptors in the pathogenesis of MS and to develop improved therapeutic strategies by targeted drug delivery using nanoformulations.
Graft-versus-Host Disease (GvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation, which causes severe damage in the small intestine, liver and skin. It is mainly mediated by T cells contained in the graft and macrophages present in transplant recipients. Unfortunately, the currently available therapies are unsatisfactory and mortality is very high. Our research interest concerns the activity of endogenous glucocorticoids in individual cell types and their impact on the pathogenesis of GvHD. Furthermore, we aim to improve the efficacy of glucocorticoid therapy of GvHD by using nanoparticles that selectively target macrophages. Using this approach, we succeeded to mitigate GvHD in a preclinical model better than the available standard therapy while concomitantly preserving the beneficial graft-versus-leukemia (GvL) effect.
Allergic asthma is a highly prevalent disease which affects more than 300 million people wordwide. It is characterized by a massive infiltration of the lung with eosinophil granulocytes leading to chronic inflammation and fibrosis of the airways. In contrast, neutrophil granulocytes are the dominant cell type in acute lung injury (ALI), an acute inflammatory disease of the lung that develops as a consequence of a variety of insults including virus infection with SARS-CoV-2. While glucocorticoids are rountinely administered in the treatment of allergic asthma, their application in the treatment of ALI remains controversial. Nonetheless, the synthetic glucocorticoid dexamethasone is still the only approved treatment for the cytokine release syndrome that often develops during ALI in Covid-19 patients. The aim of our work is to identify the mechanistic basis of glucocorticoids, in particular their cell type specific activities, and to develop new concepts to treat inflammatory lung diseases, especially by using nanoparticles.
Intestinal bowel disease (IBD) is a group of chronic inflammatory disorders of the gastrointestinal tract, which are characterized by a disturbed balance of the mucosoal immune system leading to symptoms such as bloody diarrhea and abdominal pain. Intestinal inflammation is also considered to be a major risk factor of colorectal cancer (CRC). Glucocorticoids are a mainstay in the treatment of IBD although not all patients respond to this treatment equally well. The research team of Dr. Sybille Reichardt thus aims to identify the activity of glucocorticoids in different cell types such as macrophages and intestinal epithelial cells during IBD, their molecular mode of action, and the impact of glucocorticoids on inflammation-associated tumorigenesis using preclinical models of colitis and CRC.