Research Kristien Ledeganck

Abstract

The Laboratory of Experimental Medicine and Pediatrics - within the Faculty of Medicine and Health Sciences and closely linked to the Antwerp University Hospital - focusses its research on the study of inflammation in a clinically relevant context built on interdisciplinary methodologies and collaborations. To remain in the forefront of research we perform ground-breaking experimental, as well as clinical and translational research from bench to bedside and vice versa, using innovative and high-end methodologies including organoids, rodent models, cell cultures, different next-generation omics approaches and clinical trials. We challenge you to write down a project that will have an added value to one of the research lines currently explored at LEMP (www.uantwerpen.be/en/research-groups/lemp) and briefly described below. Loss of mucosal barrier integrity is a significant contributor in the pathophysiology of mucosal inflammatory/infectious diseases (e.g. IBD, gastrointestinal cancers, RSV, COVID-19). The role of transmembrane mucins, as epithelial signalling receptors mediating barrier dysfunction, is poorly understood. Furthermore, the presence of genetic differences in mucin genes can give rise via alternative splicing to a large repertoire of structurally diverse mucin mRNA isoforms encoding similar biological functions or altering protein function resulting in progression towards disease. Currently, the mucin mRNA isoform landscape implicated in mucosal barrier dysfunction is a field to discover. Volatile organic compounds (VOCs) are compounds that are by-products of cell metabolism and induced by inflammation. The human body houses thousands of VOCs which are exhaled and can serve as non-invasive markers for disease. Hence, breathomics is applied to search for clinically relevant diagnostic, prognostic and predictive biomarkers for inflammation-related diseases in adults and children (thoracic cancers, COVID-19, asthma, COPD, BPD in neonates, gastrointestinal diseases) and to monitor the effect of air pollution on human health. However, there is a need for further identification and data mining of volatiles, linking VOCs to metabolic processes. Chronic low-grade inflammation is a key factor in obesity. As its treatment remains challenging over all age groups, research focusses on new treatment strategies for obesity, that minimize dropout and weight regain. Pathophysiological processes (hypoxia) that lead to comorbidities like cardiovascular and metabolic morbidity and obstructive sleep apnoea are also of interest. Kidney transplantation is the best treatment for patients with end-stage renal disease. As diagnosis requires invasive procedures, there is a need of sensitive, non-invasive markers of an early-stage acute rejection and the early diagnosis of glomerular damage in children and adults with various underlying diseases (diabetes, obesity or sickle cell anaemia). Visceral pain is a key feature of the gastrointestinal disorders IBD and IBS. The management of visceral hypersensitivity is challenging and requires further research towards new treatment targets. Unravelling the immunopathogenesis of chronic Hepatitis B infections is essential in the quest for novel treatment approaches. While the ineffective T-cell responses are well-known, B cells have been left largely understudied, urging a deeper understanding of the role of the humoral immune response in chronic HBV at the level of HBV-specific antibody production and of the phenotypic/functional level of B cells. Non-Alcoholic Fatty Liver Disease (NAFLD) is the global leading cause of chronic liver disease but pharmacological treatment remains poorly successful. Changes in liver hemodynamics and in parenchymal oxygenation contribute to the steatohepatitis and progressive disease worsening and are a potential drugable target. Furthermore, the role of NAFLD on extrahepatic vascular alterations contributing to cardiovascular disease warrants further study.

Researcher(s)

• Promoter: De Winter Benedicte
• Co-promoter: Adomati Tom
• Co-promoter: Lamote Kevin
• Co-promoter: Ledeganck Kristien
• Co-promoter: Smet Annemieke
• Co-promoter: Van Eyck Annelies

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

In type 1 diabetes mellitus (T1DM), insulin-producing beta-cells of the pancreas are being destroyed, resulting in excessive glucose levels and permanent need of insulin therapy. Living with T1DM is challenging. It requires intensive monitoring of glycaemia and titration of insulin in order to obtain near-normal glycaemia to reduce the risk of complications. More and more people with T1DM are being treated with insulin pumps and continuous glucose monitoring (CGM) sensors. CGM improves metabolic control and quality of life and decreases hypoglycaemia. However, currently available CGM devices also have shortcomings. They do not warn about impending ketoacidosis and do not provide information on lactate levels which can be produced during intensive exercise. Adding lactate and ketones to the equation will provide additional information on glucose fluctuations. There is an urgent need for a patient-tailored multi-biomarker device to protect against hypoglycaemia or ketoacidosis, to improve quality of life and to increase the possibilities to exercise freely. The latter is important as people with T1DM often do not perform exercise because of fear of hypoglycaemia. The main research question of this project is to evaluate the added value of measuring other biomarkers (ketones, lactate) besides glucose, in people with T1DM in daily life, but also while performing different types of exercise (anaerobic, aerobic). This will result in better algorithms to improve glycaemic control.

Researcher(s)

• Promoter: De Block Christophe
• Co-promoter: Ledeganck Kristien
• Fellow: De Ridder Francesca

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. Rejection of the transplant organ remains a major obstacle in organ survival. Histological evaluation of a kidney biopsy remains the gold-standard diagnostic tool in the detection of a rejection episode but is an invasive, costly and labour-intensive procedure. Therefore, there is a critical need for non-invasive detection and prediction methods. Donor-derived cell free DNA (ddccfDNA), present in the blood and urine of the recipient after transplantation, is a potential biomarker of allograft health. An increase in the ddccfDNA fraction might point to damage to the graft. In a prospective, longitudinal clinical trial with renal transplant recipients, we will investigate whether ddccfDNA can be used as a routine marker of allograft health by measuring the ddccfDNA fraction in blood and urine with a novel, cost effective and universal technique (non-invasive organ transplant test, NIOTT). Preliminary analysis from plasma samples of 28 recipients demonstrate the feasibility of the study protocol, the cfDNA extraction and the NIOTT methodology. In this project we will further optimise the NIOTT accuracy by use of donor DNA and the protocol to extract ddccfDNA from urine samples. After inclusion of all patients, we will investigate the ddccfDNA kinetics after transplantation in recipients with stable graft function and in transplant recipients with graft associated pathologies.

Researcher(s)

• Promoter: Abramowicz Daniel
• Co-promoter: Bosmans Jean-Louis
• Co-promoter: Ledeganck Kristien
• Fellow: Gielis Els

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project

Abstract

Researcher(s)

• Promoter: Verpooten Gert
• Fellow: Ledeganck Kristien

Research team(s)

• Laboratory Experimental Medicine and Pediatrics (LEMP)

Project type(s)

• Research Project