Medizinische Fakultät der Universität des Saarlandes
Anatomie, Zellbiologie und Entwicklungsbiologie
Sie befinden sich hier: >> Startseite >> Klinische Zentren und Einrichtungen >> Fachrichtungen Theoretische und Klinische Medizin >> Anatomie, Zellbiologie und Entwicklungsbiologie >> Univ.-Prof. Dr. med. vet. Gabriela Krasteva-Christ (Anatomie) >> Forschung / Research

Forschung / Research

Prof. Dr. Gabriela Krasteva-Christ

PubMed

 

Chemosensation / Infection

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.

Recently, we have found a subtype of epithelial cells of the airway mucosa, so called brush cells, that expresses canonical bitter receptors and the canonical taste transduction cascade of oropharyngeal taste buds (Krasteva et al., PNAS 2011). The downstream signaling cascade involves GPCRs, rise in intracellular calcium concentration [Ca2+]i,  and activation of cation channels. Brush cells respond to bacterial quorum sensing molecules and excite sensory nerve fibers, thereby eliciting aversive respiratory reflexes and local effects. 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.

Projects in our lab currently address the following questions:

(1) Which substances activate the chemosensory system in the lower airways and lung?

(2) What is the effect of brush cell activation on mucosal proliferation, inflammation, immune cells response, mucosal repair and microbiome alteration?

(3) What are the consequences of disturbed mucosal TRP channel function for the outcome in pneumonia?

(4) Do brush cells play a role in allergic and non-allergic inflammation of the airways?

(5) Generations of specific antibodies against bitter taste receptors.

 

Caveolae / Caveolin-3

Caveolae are subcellular microdomains of the plasma membrane and have a unique flask-like structure that is generated by caveolin and cavin proteins. Caveolin-3 is required for caveolae formation in skeletal and cardiac muscle cells. In the past, a large number of signaling molecules (GPCRs including muscarinic receptors) were co-purified with caveolin-3 suggesting that caveolin-3 containing caveolae are involved in intracellular signaling. Recently, we have found that caveolin-3 plays an important regulatory role in airway smooth muscle contraction. Moreover, intrapulmonary bronchi of mice deficient for caveolin-3 were hyperreactive to contractile stimuli such as acetylcholine (Keshavarz et al., Sci Rep. 2018). Since airway hyperreactivity is a hallmark of asthma and COPD, we are interested to elucidate the regulatory role of caveolin-3 for changes in intracellular Ca2+-levels in the constrictor response to contractile stimuli. Finally, we would like to use the knowledge for therapeutic modulation of bronchial hyperreactivity.

 

Research interests of the postdocs in the lab:


Dr. Monika Hollenhorst

PubMed


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

PubMed

 

My current research focuses on a fundamental question in the biomedical field: “How do we study human disease-causing genes which are absent in mice and rats?” I have been fascinated 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 ideal rodent model to study disease-relevance due to the lack of or restricted access to quality human tissue samples. With my expertise in molecular genetics (PhD degree from the University of Bonn, Germany) and further postdoctoral training (Stanford University, USA), in which I have generated mouse models to study neurological disorders, I seek to establish the disease-relevance of these respective genes in alternative rodent models applying a broad set of established as well as cutting-edge molecular biological techniques.

 

 

Current funding

DFG, TRR 152, HOMFOR, Industry

 

Join us!

We are always interested in recruting motivated graduate students and postdocs. If you are interested in joining our group, please contact us (anatomie.sekretariat.krasteva-christ @uks.eu) with a statement of research interests, your CV and contact information of two referees. Prospective postdocs should apply early so that financial support through third party funding can be explored.

We also have a number of short-term/thesis projects available for motivated master students and MD students. We are looking forward to hearing from you to discuss potential projects.