Group leader: Karen Uray, Ph.D. (karen.uray@med.unideb.hu)
Group members:
Tibor Docsa, PhD
Alexandra Keserű, PhD student
Luca Varga, Ph.D student
Job Baffin Kola, Ph.D student
Mubashra Inam, MS student
Rima Jafo, MS student
Khashiya Khathoon, MS student
Research background:
Feeding intolerance due to ileus, caused by slowed gastrointestinal motility, are common complications in post-surgical patients and critically ill and trauma patients. Feeding intolerance causes delayed enteral feeding, prolonged hospital stays, increased complications, and increased patient care costs; however, there are no effective pharmacological treatments for ileus. Existing prokinetic drugs, drugs that increase gastrointestinal motility, target the enteric nervous system. However, we and others have shown that gastrointestinal smooth muscle is dysfunctional in ileus animal models. Phosphorylation of myosin light chain is the rate-limiting step in smooth muscle contraction; thus, our research is focused on the dysregulation of myosin light chain (MLC) phosphorylation during the development of ileus. Our long term goal is to identify drug targets in intestinal smooth muscle for the treatment of postoperative and trauma-induced ileus.
Inflammation is a key component of ileus and one of our objectives is to determine the mechanism by which inflammatory cytokines affect the regulation of MLC phosphorylation. We found that CXCL1 and LIX are both upregulated early in the development of ileus. Thus, we are investigating how these cytokines, which signal via C-X-C Motif receptor 2 (CXCR2), decrease MLC phosphorylation to inhibit smooth muscle function. The results of these studies will improve our understanding of how cytokines can affect gastrointestinal motility and provide a basis for pursuing novel drug targets in the CXCR2 signaling cascade for the treatment of ileus.
Another avenue of research is the role of mechanotransduction in the development of ileus. We showed that increased cyclical stretch induced the increased secretion of CXCL1. We are currently examining the signaling pathways involved in stretch-induced CXCL1 secretion.
We also collaborate with several other research groups exploring the effects of metabolites on intestinal motility (Péter Bai) and changes in intestinal motility in Huntington’s Disease (Krisztina Tar).
Publications: