KARL TRYGGVASON

Address:
Karl Tryggvason, M.D., Ph.D., Professor
Address: Biocenter and Department of Biochemistry
University of Oulu
P.O.Box 400
FIN-90571 Oulu, Finland

or: Division of Matrix Biology
Department of Medical Biochemistry and Biophysics
Karolinska Institute
S-17177 Stockholm, Sweden

Phone:
+358-8-553 1200 (Finland) or +46-8-728 7720 (Sweden)
Fax:
+358-8-553 1141 (Finland) or +46-8-316 165 (Sweden)
e-mail:
karl.tryggvason@mbb.ki.se

MOLECULAR BIOLOGY AND PATHOLOGY OF BASEMENT MEMBRANES

Basement membranes are present in all tissues where they promote cell differentiation, migration and adhesion. They also have specific functions, such as in the kidney where they form the macromolecule filter of the glomerular filtration barrier. Structural changes in basement membranes are major causes of complications in many diseases, such as diabetes and several disorders of muscle, skin and kidney. The overall goals of this project are to characterize the structure and nature of basement membrane proteins and some extracellular proteinases and their genes, and to examine their alterations in diseases. The research group, which currently consists of 29 persons, has cloned human and mouse genes for most basement membrane proteins and shown mutations leading to diseases such as Alport syndrome (hereditary nephritis), diffuse leiomyomatosis, epidermolysis bullosa and muscular dystrophy. We have also characterized two extracellular metalloproteinases (type IV collagenases, gelatinases) and studied their expression during development and in cancer. Furthermore, we have identified a novel bacteria-binding macrophage receptor with collagenase structure. The immediate goals of the project are to extend our studies, the specific aims being:

• To study the regulation of the type IV collagen a5(IV) and a6(IV)chain genes and develop gene therapy for Alport syndrome.
• To elucidate the function of various laminin chains using recombinant proteins and, particularly, elucidate the biological role of the novel g2 and a4 chains. Furthermore, emphasis is laid on the characterization of mutations in the a2 chain gene in muscular dystrophy.
• To determine the tertiary structure of the two type IV collagenases and elucidate the regulation of their genes and biological function of the enzymes using transgenic animal technologies.
• To isolate the gene causing congenital nephrotic syndrome, which is characterized by extensive leakage of blood proteins through the glomerular basement membrane.
• To further characterize the nature and physiological role of the novel macrophage receptor, MARCO, using transgenic animals and other molecular biology and protein techniques.

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