Projects
Longitudinal and Bayesian modelling of polyomavirus nephropathy and rejection after kidney transplantation KU Leuven
Since the beginning of clinical kidney transplantation, more than 60 years ago, immunosuppression aimed to reduce the incidence of acute rejection. Despite the current use of powerful immunosuppressive agents, primarily targeting T-cell activation, and despite improvement on the short term, graft outcome on the long term has improved only marginally. The reason for graft failure after kidney transplantation is primarily progressive ...
Development of new antimicrobials: Rational design of polyomavirus and mycobacterial inhibitors KU Leuven
Persistent, untreatable infections pose a substantial financial and medical burden on society. Mycobacterium tuberculosis (Mtb) and BK polyomavirus (BKV) are two endemic species that have persisted for more then a century and over 60 years, respectively. Both infections present ongoing challenges to the public health. Within this thesis, novel lead compounds targeting both infections were discovered. In the first part, the thesis focussed on ...
Unravelling the role of BK polyomavirus genetic variants in viral pathogenicity and clearance in kidney transplant recipients KU Leuven
BK polyomavirus is the first human polyomavirus discovered in the early 70s in a kidney transplant patient. The immunosuppression state of the patient can lead to reactivation of the virus, leading in 30% of the case to graft loss. Up to now, no protocol for the management of BKPyV associated nephropathy has been established. The combination of immunosuppressive drug tapering and cidofovir (an anti-DNA virus agent) permits in many cases to ...
Fragment-based drug design of antivirals targeting the polyomavirus capsid and flaviviral NS3-helicase KU Leuven
BK and JC viruses are closely related, non-enveloped, pathogenic DNA viruses of the polyomavirus family for which there are no approved treatments. These viruses cause latent infection in humans and have an extremely high prevalence worldwide (70-90% of the population is seropositive). However, clinical manifestation is seen only in immunocompromised patients which can lead to severe and often fatal complications. BK virus for instance, is a ...
Unraveling the role of BK polyomavirus variants and of cellular CMP kinase on viral pathogenicity and clearance in renal-transplant patients KU Leuven
The results obtained with our project provide the possibility for doctors who treat BKPyV reactivation in renal transplant patients to classify the patients according to the risk of viremia development and the sensitivity to cidofovir-based treatment. The genotypic characterization of the BKPyV strain and the cellular CMP kinase gene can identify which subgroup of patients is in at risk and which may benefit from treatment.
Structure-guided design of BK/JC virus capsid targeting antivirals KU Leuven
BK and JC viruses are closely related members of the polyomavirus family that latently infect 70-90% of humans and cause fatal clinical complications in immunocompromised patients (kidney failure and brain demyelination). There are no effective drugs to treat these infections. The lack of conventional, enzymatic antiviral targets such as proteases or integrases makes any development challeging. The small genome of polyomaviruses encodes two ...
MERKEL CELL CARCINOMA, TOWARDS THE IDENTIFICATION OF NOVEL MOLECULAR TARGETS AND THE ESTABLISHMENT OF A THREE-DIMENSIONAL CELL CULTURE MODEL KU Leuven
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma. Nevertheless, its incidence has increased in the last few years and this trend is predicted to persist. Furthermore, with a general mortality rate of 33-46% and a high rate of recurrences, it is one of the most aggressive types of skin cancer. Currently, MCC has two recognized etiologies. Merkel cell polyomavirus (MCPyV) DNA is found clonally integrated in the genome of ...
Correlations between blood and allograft gene expression signatures to improve the diagnosis and monitor treatment of kidney transplant rejection. KU Leuven
Kidney transplantation is the preferred treatment for end stage renal disease. However, allo-reactive immune response against the donor kidney can lead to rejections and increased risk of graft dysfunction or loss. Depending on the immune mechanism involved, rejections can be classified as antibody-mediated rejection (ABMR), T cell-mediated rejection (TCMR), and mixed rejections. Next to rejection, also signs of over-immunosuppression hamper ...
Design and developement of diagnostics and drugs for neurodegenerative, immunological and microbial diseases KU Leuven
The research aims at two important goals:
1) The development of (fluorescent) tools to visualize biomarkers in neurodegenerative diseases as research tools or diagnostics
In this part of the work fluorescent molecules are developed and optimized. Key goals are to increase the biocompatibility, stability, specificity and (to later enable in vivo imaging applications) a suitably red-shifted fluorescence. Key biomarkers of ...