Nephrology Research Laboratory

Research description:

Research interest is focused on two main topics: glomerular diseases and transplantation immunology. Glycobiology-related research projects currently running are aimed at delineating the role of heparan sulfate proteoglycans at the structure-functional level in proteinuria and (glomerular) inflammation. In addition, the role of the heavily glycosilated glomerular a-dystroglycan in normal podocytes and glomerular pathology is investigated.

Research Goals:

Elucidation of the role of heparan sulfate proteoglycans at the structure-function level in proteinuria, in particular the role of heparanase.
Elucidation of the role of heparan sulfate proteoglycans at the structure-function level in glomerular inflammation, in particular the role of HS in adhesion of leukocytes to endothelial cells.
Identification of the mechanisms that lead to podocyte dysfunction/loss in proteinuric diseases, in particular the role of (the carbohydrates on) glomerular a-dystroglycan.

Key results:

Upregulation of glomerular heparanase expression in several (experimental) proteinuric diseases characterized by loss of HS in the glomerular basement membrane (GBM).
Identification of specific HS structures at the surface of glomerular endothelial cells that are important for the adhesion of leukocytes.
Important role of the carbohydrates on glomerular a-dystroglycan for its interaction with laminin and agrin in the GBM.

Anticipated Results:

Development of glycomimetics that can influence glomerular inflammation (inhibition of leukocyte recruitment and adhesion) and proteinuria, i.e. glomerular HS degradation (inhibition of heparanase).
Elucidation of the role of glomerular a-dystroglycan in normal podocytes and glomerular pathology.

Main Projects (currently running or recently finished):

Functional properties of heparan sulfate proteoglycan domains in renal physiology and pathology (NWO, 1 pHD student, finished).
The significance of a disturbed heparan sulfate synthesis and degradation for diabetic glomerular pathology (DFN, 1 pHD student).
Development of new alfa-dystroglycan antibodies and evaluation of the agrin/dystroglycan complex (NSN/ISIS, 1 technician).
Role of glomerular endothelial heparan sulfate in adhesion of leukocytes. New leads for treatment of glomerulonephritis? (NSN, 1 post-doc, 0.3 technician).

For further information, we refer to out website at NCMLS or UMCN