Head of LEMP: Benedicte De Winter
The Laboratory of Experimental Medicine and Pediatrics (LEMP) incorporates 7 clinical divisions within the Faculty of Medicine and Health Sciences and is closely linked to the Antwerp University Hospital. LEMP has a strong track record in a broad range of diseases affecting several organs including the lungs, gastrointestinal tract, liver, pancreas, kidneys, endocrine glands, and fat tissue.
LEMP research focusses 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 thereby using innovative and high-end methodologies including organoids, rodent models, cell cultures, different next-generation omics approaches, …, and clinical trials.
Loss of mucosal barrier integrity is a significant contributor in the pathophysiology of mucosal inflammatory/infectious diseases (e.g. IBD, gastrointestinal cancers, respiratory tract infections (RSV, COVID-19)), but the role of transmembrane mucins, as epithelial signalling receptors mediating barrier dysfunction, is poorly understood. Upon inflammation, aberrantly expressed transmembrane mucins are likely to be the first point of contact between host tissue and the microbiota. Furthermore, the presence of genetic differences in mucin genes can give rise to a large repertoire of structurally diverse mucin mRNA isoforms via alternative splicing 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 scientific field to discover.
Volatile organic compounds (VOCs) are compounds that are byproducts of normal cell metabolism and are induced due to inflammatory processes. The human body houses thousands of these VOCs which are exhaled and thus can be used as non-invasive markers for health and disease. Therefore, LEMP explores breathomics in search for clinically useful diagnostic, prognostic and predictive biomarkers for inflammation-related diseases in adults and children (thoracic cancers, COVID-19, lung diseases including asthma, COPD, pollution-related disease, BPD in neonates, gastrointestinal diseases such as IBS and IBD) and to monitor the effect of air pollution on human health. In addition, clinic and biology are linked in translational volatomic research where VOCs are studied in the headspace of cell lines and in animals (mice, sheep). As the research field is rapidly expanding, there is a need for further identification of volatiles, linking volatiles to metabolic processes and to find clinically relevant biomarkers.
As a strong believer in bench-to-bedside research, LEMP encourages the inclusion of clinical studies in our research lines. Clinical research in obesity and its comorbidities are an important subject in LEMP, both in adult and pediatric patients, as chronic low-grade inflammation is an important factor in the pathophysiological processes of obesity. This multidisciplinary research line mainly focuses on cardiovascular and metabolic morbidity in these patients, as well as the additional effects of obstructive sleep apnea. As the treatment of obesity remains challenging over all age groups, an important topic to study is the development of new treatment strategies for obesity, that minimize dropout and weight regain. Also, the pathophysiological processes that lead to obesity-related comorbidities (such as hypoxia) are important factors to study.
In clinical practice, many diseases remain challenging to diagnose correctly, therefore LEMP is continuously looking for ways to improve diagnosis by replacing or supporting invasive methods with reliable minimally invasive biomarkers. In nephrology, kidney transplantation is the treatment of choice for patients with end-stage renal disease; however, the golden standard for diagnosis still is a needle biopsy. Therefore, there is an unmet clinical need of sensitive, non-invasive markers that allow for the detection of acute rejection in an early stage. Besides the early diagnosis of glomerular damage in children and adolescents with various underlying diseases such as diabetes, obesity or sickle cell anemia remains a challenge. Proteinuria (micro-albuminuria and macro-albuminuria) is currently the most sensitive early marker of glomerular damages and widely used as a predictor for nephropathy, however, there is evidence that it might not be the optimal marker for early detection of kidney disease. Therefore, more sensitive and specific biomarkers than microalbuminuria are urgently needed to early detect kidney disease.
Visceral pain is a key feature of two major gastrointestinal disorders: IBD and IBS. The management of visceral hypersensitivity still remains a challenge and therefore, further research towards new treatment targets is of utmost importance. In order to study the pathophysiology underlying visceral hypersensitivity and potential receptors or mediators that could be involved, two very elegant techniques are available in our lab, namely the in vitro afferent nerve activity and the in vivo visceromotor response to colorectal distension.
Humoral immunity in Hepatitis B infections: Insights into the immunopathogenesis of chronic HBV infections are fundamental in the quest for novel treatment approaches aimed at a functional cure. While much is known about the ineffective HBV-specific T-cell responses that characterise persistent HBV replication, B cells have been left largely understudied. This warrants 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 and functional level of B cells. The recent development of fluorescently labelled HBV proteins should fuel novel research into the mechanisms behind dysfunctional HBsAg-specific and fluctuating, possibly pathogenic, HBcAg-specific B-cell responses in chronic HBV. Finally, novel immunomodulatory treatments that partly target B cells are currently in clinical development, but a detailed assessment of their impact on HBV-specific B-cell responses is lacking.