EURAMY

Per Westermark

Uppsala University, Sweden

E-mail: Per.Westermark@genpat.uu.se
Phone: +46 18 611 3849

Overall research program
The Amyloid Laboratory in Uppsala, led by Professor Per Westermark, focuses on the nature and pathogenesis of different amyloid diseases. The group has made a number of important discoveries, including the characterization of several of the 26 known main amyloid fibril proteins, e.g. wild-type transthyretin in senile systemic amyloidosis and apolipoprotein AIV in a very rare systemic amyloidosis. Ongoing work is focused on the mechanisms by which systemic AA-amyloidosis is transmissible in animals, heterogeneity in transthyretin amyloid diseases and analyses of the variations of tissue distribution in systemic amyloidoses, particularly AL-amyloidosis.

Five key publications
1. K Lundmark, GT Westermark, A Olsén, P Westermark: Protein fibrils occurring in
nature can induce AA amyloidosis in mice: cross-seeding as a disease mechanism
Proc Natl Acad Sci USA 102, 6098-6102, 2005

2. J Bergström, Å Gustavsson, U Hellman, K Sletten, CL Murphy, DT Weiss, A
Solomon, B-O Olofsson, P Westermark Amyloid deposits in transthyretin-derived
amyloidosis: Cleaved transthyretin is associated with distinct amyloid morphology
J Pathol, 206, 224-232, 2005

3. K Lundmark, GT Westermark, S Nyström, CL Murphy, A Solomon, P Westermark:
Transmissability of systemic amyloidosis by a prion-like mechanism
Proc Natl Acad Sci USA 99, 6979-6984, 2002

4. K Ganowiak Johan, GT Westermark, U Engström, Å Gustavsson, P Hultman,

P Westermark: Acceleration of AA-amyloidosis by amyloid-like synthetic fibrils
Proc Natl Acad Sci USA 95, 2558-2563, 1998

5. P Westermark, K Sletten, B Johansson, GG Cornwell III: Fibril in senile systemic
amyloidosis is derived from normal transthyretin Proc Natl Acad Sci USA 87:2843-
2845, 1990

Jin-ping Li
Uppsala University, Sweden

E-mail: jin-ping.li@imbim.uu.se
Phone: +46 18 471 4241

Overall research program

The main research area of this group is biosynthesis, structure and functions of heparan sulfate (HS), a ubiquitous glycosaminoglycan. It is suggested that interaction between amyloid proteins andheparan sulfate is central to amyloidosis. We found that overexpression of heparanase, a HS-cleaving enzyme, confers resistance to murine AA-amyloidosis. We intend to (a) characterize the change in HS metabolism due to heparanase overexpression; (b) define the mode of interaction between HS, SA-peptide monomer and aggregate; (c) investigate the effect of overexpressing heparanase on amyloid formation, using experimental AA-amyloidosis models and heparanase transgenic/knock-out animals; (d) structurally characterize HS isolated from patients with AA-amyloidosis; (e) explore a strategy, using the murine AA-amyloidosis model and appropriate cell culture systems, to attenuate amyloid generation by administration of HS-based oligosaccharide drugs.

Five key publications
1. JP Li, ML Galvis, F Gong, X Zhang, E Zcharia, S Metzger, I Vlodavsky, R Kisilevsky,
U Lindahl (2005) In vivo fragmentation of heparan sulfate by heparanase
overexpression renders mice resistant to amyloid protein A amyloidosis. Proc Natl
Acad Sci U S A 102:6473-7

2. J Kreuger, P Jemth, E Sanders-Lindberg, L Eliahu, D Ron, C Basilico, M Salmivirta,
U Lindahl (2005)
Fibroblast growth factors share binding sites in heparan sulphate. Biochem J
389:145-50.

3. E Zcharia, S Metzger, T Chajek-Shaul, H Aingorn, M Elkin, Y Friedmann,
T Weinstein, JP Li, U Lindahl, I Vlodavsky (2004)
Transgenic expression of mammalian heparanase uncovers physiological functions
of heparan sulfate in tissue morphogenesis, vascularization, and feeding behavior.
FASEB J 18:252-63.

4. J Ledin, W Staatz, JP Li, M Gotte, S Selleck, L Kjellen, D Spillmann (2004)
Heparan sulfate structure in mice with genetically modified heparan sulfate
production. J Biol Chem 279:42732-41.

5. B Lindahl, U Lindahl (1997) Amyloid-specific heparan sulfate from human liver and
spleen. J Biol Chem 272:26091-4.