Ongoing Projects

Regulating effect of miRNAs on MHC Class II antigen presentation in human monocytic cell lines and primary cells

MHC class II molecules play vital roles in presenting foreign antigens on the cell surface of the antigen presenting cells, a critical step in adaptive immune responses. Clinically, changes in peptide-loaded MHC-II (HLA-DR) expression on monocytes have contributed to reliable diagnosis, prognosis, and prediction of sepsis. In an immunosuppressed state, monocytic HLA-DR surface expression is significantly down-regulated. In our lab we have been establishing and conducting a series of flow cytometry-based miRNA transfection paradigms, both in human cell lines and primary cells, with an overarching goal to identify and validate specific miRNA molecules as potential diagnostic biomarkers in peripheral blood and/or novel therapeutic options for early sepsis.

Establishing zebrafish as a model organism for anesthesia-induced neurotoxicity assessment during neural development and in adulthood and for identifying neuroprotectants in vivo

Over the past decade, a large and growing body of preclinical studies have demonstrated (developmental) neurotoxic effects of various anesthetics in laboratory animals. While such study outcomes have raised considerable concerns for administrating anesthetics especially in young children, significant limitations arose when translating the preclinical observations into clinical practice. It is of pivotal importance in this research area to establish a robust animal model that helps identify valid clinical endpoints that reliably reflect postoperative cognitive dysfunction (POCD) among different age populations, develop potential anesthetic adjuvant and discover novel target-specific neuroprotective agents for better and safer anesthetic management.

Regulation of the nociceptin system and mechanisms involved in

Nociceptin (N/OFQ) and its receptor share high homology with opioid ligands and the classical opioid receptors and are involved in a wild rang of physiological responses, including pain and inflammation. Preclinical and clinical studies have suggested that compounds targeting the nociceptin system may be safe and effective alternatives to opioids in the treatment of pain or inflammatory disorders. The aim of this project is to investigated the crosstalk between the nociceptin and the TLR system in human blood leukocytes and possible mechanisms involved. Fundamental insights into the regulation of the nociceptin system in circulating blood during immune response may shed new lights on the treatment of pain and/or inflammatory disease.

Clinical and Molecular Pain Research

Each year more than 300 million surgeries are performed worldwide. Although much progress has been seen in the treatment of pain using multimodal treatment strategies and improving organizational structures by implementing acute pain services, pain after surgery is still an unresolved problem. There are large inter-individual differences in postsurgical pain, pain-related functional impairment, and analgesic requirements. Severe acute pain can transform into chronic postsurgical pain, resulting in long-term disability, suffering, and decreased quality of life. Our research focus is to identify factors which contribute to the variability of pain outcomes, the development of chronic postsurgical pain, and differences in analgesic requirements. The Clinical and Molecular Pain Research Group is currently investigating a variety of pain-related topics: 

• Metabolism of drugs

Genetic diversity influences the efficacy and safety of various classes of drugs, including analgesics. In recent years, promising candidate genes have been identified – for example, drug-metabolizing enzymes having a major impact on postoperative analgesia and success of treatment of opioid-mediated side effects of postoperative nausea and vomiting. This includes CYP2D6-dependent metabolism of drugs like tramadol, codeine, and oxycodone, as well as tricyclic antidepressants used in chronic pain management (e.g., amitriptyline) and antiemetics.

• Pain sensitivity and neuropathic pain

Genetic polymorphisms have been linked to varying pain sensitivity, development of specific chronic pain diseases, the risk of chronic postsurgical pain, and specific pain characteristics, such as neuropathic pain. Study results are equivocal so far; thus sufficiently powered trials would be of considerable clinical interest.

• PAIN OUT

As part of an international pain registry, we collect standardized patient data for the perioperative period, including validated patient questionnaires on pain-related short-term and long-term outcomes. This registry enables internal benchmarking for quality control of postoperative pain management, and provides a well-phenotyped cohort which can be analyzed in our department for clinical and genetic.