Research Projects in the Krasteva-Christ Lab
Univ.-Prof. Dr. med. vet. Krasteva-Christ
Chemosensation / Infection / Immunity
Airway epithelial cells line the respiratory tract and come early on in close contact with invading pathogens. Expression of various trans-membranous and cytosolic pathogen recognition receptors (PRRs) allow the detection of pathogens by the epithelium resulting in complex changes in gene expression and subsequent release of pro-inflammatory mediators (e.g., cytokines, etc.) and other immunomodulatory factors.
In the last decade a subtype of epithelial cells of the airway mucosa termed brush cells, which expresses canonical bitter receptors and the canonical taste transduction cascade of oropharyngeal taste buds emerged as important modulators in immunity Hollenhorst at al., J Clin Invest. 2022. The downstream signaling cascade involves GPCRs, rise in intracellular calcium concentration [Ca2+]i, and activation of cation channels Hollenhorst et al., FASEB J. 2020, Kumar et a., Cells, 2022. Brush cells respond to bacterial quorum sensing molecules and excite sensory nerve fibers, thereby eliciting aversive respiratory reflexes and local effects Krasteva et al., Proc Natl Acad Sci U S A. 2011, Krasteva et al., Life Sci. 2012, Hollenhorst et al., J Clin Invest. 2022. In particular, we are interested in identification of the molecular steps that transform detection of pathogens into inflammatory events that are essential for host defense competence and tissue homeostasis. Specifically, we study the interplay between various cells types in the airways and the autonomic nervous system.
Projects in our lab currently address the following questions:
- What is the effect of brush cell activation on mucosal proliferation, inflammation, immune cells response, mucosal repair and microbiome alteration?
- Do brush cells mediate signals to other organs?
- What are the consequences of disturbed mucosal TRP channel function in the airways in the context of bacterial infection?
- What is the contribution of sex/gender to shape the brush cells mediated immune responses in the airways?
- As members of the core research area NanoBioMed, we aim to discover new targets and drugs for treatment of pneumonia by combining cutting-edge experimental and computational techniques.
Research Topics of the Scientific Staff
Dr. Monika Hollenhorst
Strict regulation of airway transepithelial ion transport is a key factor for a functional mucociliary clearance. Disruption of this process can lead to diseases with severe pulmonary phenotype such as cystic fibrosis, in which the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is defective. Therefore understanding the regulation of transepithelial ion transport is crucial. During my PhD at the Justus-Liebig-University in Gießen I was working on the non-neuronal cholinergic system of the airways and its role in the regulation of transepithelial ion transport. There I obtained my training in electrophysiological methods, such as Ussing chamber, two electrode voltage clamp and patch clamp. I could deepen my experience in airway epithelial physiology during my time as a postdoctoral researcher at the National Childrens’ Research Centre in Dublin and at Inserm in Paris while working on cystic fibrosis and inflammation resolving molecules. My current research interests lie in the investigation of ion transport processes in the airway epithelium with electrophysiological methods. Special focus is the investigation of the cholinergic system and the role of nicotinic acetylcholine receptors in airway physiology.
Dr. Stephan Maxeiner
My current research focuses on a fundamental question in the biomedical field: “How do we study human disease-related genes which are absent in mice and rats?” I have always been intrigued by the observation that homologues of numerous human disease-relevant genes are absent in mice, rats and hamsters escaping thorough genetic analyses and, consequently, genetic manipulation. In contrast, the guinea pig retains these homologous genes making it an attractive model to study disease-relevance complementing limited access to quality human tissue samples. With my expertise in molecular genetics (PhD degree from the University of Bonn, Germany) and further postdoctoral training in molecular neuroscience (Stanford University, USA), in which I have focused on studies regarding neurological disorders, I seek to establish the disease-relevance of these genes applying a broad set of established as well as cutting-edge molecular biological techniques.
In the center of my interest are genes of the pseudoautosomal region, PAR, a particular region on both mammalian sex chromosomes (X- and Y-chromosomes), which during male meiosis undergoes recombination and behaves like autosomes. The genes on PAR are set in a specific order, despite that during mammalian evolution some remain strictly pseudoautosomal and others ended on the X-specific part on the X-chromosome. A limited number eventually developed into Y-specific “gametologues” (Maxeiner et al., Anal Anat. 2021). Among them are, e.g., AMELX/AMELY as well as NLGN4X/NLGN4Y. For the latter gene pair, we could develop novel PCR strategies to infer the presumptive biological sex from given human DNA samples (Maxeiner et al., Biol Sex Differ. 2019). Differences between ancestral mammalian PAR genes and todays human X-restricted, i.e., previously ancestral PAR genes, might emerge as interesting candidates differing in the outcome of human diseases regarding the sex/gender of the individual.