Projects
Antimicrobial dosing in critically ill patients with severe sepsis and septic shock: a novel patient-oriented and covariate driven approach KU Leuven
We ultimately aim to disseminate new dosing algorithms for several deliberately chosen antimicrobials/antifungals into daily clinical ICU practice in order to achieve therapeutic and non-toxic exposure. This project exemplifies a translational and multidisciplinary research approach starting from a clinical question, integrating data from more fundamental exploration of covariates into clinically usable dosing algorithms and finally ...
STOP_SEPSIS: investigation into a new concept of sepsis, the greatest unmet medical need of our times. Ghent University
As sepsis hits 49 million people per year, killing 11 million of them, it is the most urgent unmet medical condition of today. In the best mouse model of sepsis, the CLP model, we have found that lethality is linked to loss of function of the transcription factor PPARa in hepatocytes. PPARa is the coordinator of fatty acid beta oxidation and ketogenesis, i.e. the transformation of free fatty acids (FFAs) into acetyl-coA and ketone bodies ...
Investigation of the mechanism of the loss of function of HNF4a-PPARa axis in polymicrobial sepsis. Ghent University
Sepsis hits 49 million people per year, killing 11 million of them (1200 people per hour). Our lab has found that lethality in sepsis is strongly linked to loss of function, in the liver, of the transcription factor PPARa, which is the major coordinator of the transformation of free fatty acids (FFAs) into ketone bodies (KBs). These FFAs are massively released from fat and hence in sepsis they accumulate in tissues and fail to transform to ...
Investigating the protective role of the glucocorticoid receptor against lactate-mediated lethal shock in sepsis Ghent University
With a yearly burden of 11 million deaths, sepsis is a gigantic unmet medical need, caused by a host-pathogen interaction going completely wrong. Despite decades of research, the current management of sepsis remains supportive rather than curative. Clinical trials in sepsis have mainly been focused on targeting the inflammatory pathway, but without success. Our research group has found that sepsis is also accompanied with extensive hepatic ...
Investigating the impact of neutrophil extracellular traps and peptidylarginine deiminase 4 in Gram-positive sepsis KU Leuven
Sepsis is a significant health care problem, with mortality rates remaining at 30% despite years of research and implementation of new intervention therapies. The pathologies of sepsis result not only from an infection, but also from the hyperinflammatory host response. Most research, particularly in animal models, is currently on polymicrobial sepsis or Gram-negative bacterial products, which does not necessarily match the clinical cases of ...
Profound study of the anti-inflammatory mechanism and therapeutic significance of GILZ in endotocemia ans sepsis. Ghent University
Sepsis is a dondition usally resulting from infection and leading to admission in Intensive Care Units. Sepsis forms a huge unmet medival need since the mortality rate is about 40% and new therapies are not emerging. Glucocorticoids (GCs) are popular anti-inflammatory drugs, but still three major problems are associated with GCs: the anti-inflammatory mechanism is unclear, there are a lot of GC unresponsive patients, and GCs display serious ...
Integrative interactome and protein modification analysis of HNF4α in sepsis Ghent University
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Recent insights have endorsed the importance of energy metabolism in the pathophysiology, governed by the liver. Previous research by our group links the downregulation of certain metabolic genes in sepsis to a loss of function and reduced DNA-binding activity of HNF4α, a key transcription factor. The transcriptional activity of nuclear ...
Investigating the role of hemolysis in polymicrobial sepsis. Ghent University
Sepsis is defined as a life-threatening organ dysfunction resulting from a maladaptive host response to an infection. It is considered the most urgent unmet medical need of this time, as it accounts for approximately 20% of all global deaths (Singer et al, 2016; Reinhart et al, 2017; Rudd et al, 2020). Several clinical studies have shown that sepsis leads to intravascular hemolysis, being accompanied with an increased risk of death (Adamzik ...
Developing a broadly protecting vaccine against polymicrobial sepsis. Ghent University
WHO has recently labeled sepsis as a most urgent unmet medical need With 30 million cases and 8 million deaths yearly (including 3 million children) sepsis is indeed very prevalent The infectious bacterial agent is unpredictable, but mostly belongs to a shortlist of about 10 species, and bacterial septic pneumonias and peritonitis share a number of overlapping contaminants In a mouse model of polymicrobial septic peritonitis, we have ...