The overall aim of our work in the Protease Inhibitor Group is given on the project main page. Most of the immediate research tasks performed are centered around the ALF funded project “Cystatin C – marker for kidney function, biomarker in cancer and model for treatment of amyloidosis”. This project deals with three lines of clinically oriented research, emanating from three distinct properties of the small protein cystatin C. Each line of research has its distinct clinical aims, but the methods employed and expertise needed are highly overlapping. The overall project goal is to improve our diagnostic tools in kidney disease and cancer (with a focus on melanoma), with an additional ambition to reveal potential anti-tumoural and anti-amyloidogenic substances. 

In order to develop new diagnostic strategies for kidney disease we aim to evaluate new urine markers and to characterize the new syndrome called 'shrunken pore syndrome', in which the functional pores in the glomerular basement membranes are reduced.

To elucidate the diagnostic and therapeutic potential of cystatin C in cancer, we aim to develop antibody- and MS-based assays for cystatin C, other cystatins and their target enzymes, in order to investigate melanoma patient samples. We specifically work on the cellular mechanism leading to uptake of cystatin C and other cystatins and functional consequences of this process.

To address new potential treatments for amyloid disease we aim to perform structural and physiological studies of O-glycosylated cystatin C and its potential role in the development and diagnosis of Alzheimer’s disease. We also study L68Q-cystatin C, the protein variant causing Hereditary Cystatin C Amyloid Angiopathy (HCCAA) in young adults and the process when monomeric cystatin C is transformed into cystatin C amyloid fibrils. Prevention of amyloid formation is addressed by design and use of oligomer-specific antibodies and synthetic low-molecular-mass substances.

Results from the project should be of direct clinical relevance for improved diagnosis of kidney disease, will contribute to our understanding of the protease-antiprotease system in melanoma and provide diagnostic tools for potential use in cancer diagnostics in the near future. It could lead to development of new analytic tools to detect amyloid in clinical samples as well as substances that can interefere with amyloid formation and hence be of possible value for treatment of amyloidosis.