Current projects include the investigation of the genetic basis of metamizole-induced agranulocytosis, and the analysis of cell-free DNA as a non-invasive method to detect and monitor allograft injury in organ transplant recipients and circulating tumor DNA in patients with cancer.
Liquid biopsy using cell-free DNA
Cell-free DNA (cfDNA) is released into the circulation and other body fluids as short DNA fragments through the process of cell death and cell turnover. As a consequence, cfDNA in peripheral blood or urine can be used to detect somatic genetic variation, i.e. genetic alterations that are specific to a given tissue, without directly accessing the tissue itself. This approach, also known as “liquid biopsy”, is of particular interest in the context of cancer and solid organ transplantation where the tissue of interest (tumor, organ allograft) differs genetically from other cells and tissues.
In collaboration with the Department of Nephrology (Inselspital) and Visceral Surgery (Inselspital), we are investigating the detection and quantification of donor-derived cfDNA in plasma and urine from kidney recipients in order to evaluate potential applications of this "liquid biopsy" approach in the management and monotoring of organ transplant recipients. In collaboration with the Institute of Pathology (University of Bern) and the Department of Urology (Inselspital), we are conducting a study in patients with muscle-invasive bladder cancer to investigate the potential prognostic value of tumor-derived cfDNA to identify patients at increased risk of disease recurrence after radical cystectomy.
Genetics and mechanisms of metamizole-induced agranulocytosis
Idiosyncratic adverse drug reactions (ADRs) are adverse effects from medications that occur independently of the intended mechanism of action of a drug. They can occur at any dose and are rare and unpredictable. The consequences for patients suffering from idiosyncratic ADRs are often dramatic. Metamizole is an analgesic and antipyretic drug widely used in many parts of the world, including Switzerland. Although metamizole has a favorable overall safety profile, susceptible patients can experience agranulocytosis, a severe and potentially fatal loss of neutrophil granulocytes. To date, the mechanisms underlying metamizole-induced agranulocytosis are poorly understood, making it impossible to predict in whom this life-threatening adverse effect is likely to occur.
In collaboration with a multidisciplinary team encompassing researchers from the University Hospital Basel (Clinical Pharmacology & Toxicology) and the Inselspital Bern (Drug Allergy Research Laboratory), this SNF-funded project aims to investigate mechanisms and genetic factors underlying metamizole-induced agranulocytosis. Specifically, our group will perform a genetic association study to identify genetic risk factors for this severe adverse drug reaction. Since some idiosyncratic ADRs are known to be the result of an immune response triggered by the drug, genetic variation related to the immune system is of particular interest in this project.