2012 © Institute for Molecular Medicine Finland FIMM
Principal Investigator Taina Pihlajaniemi
Principal Investigator:
Taina Pihlajaniemi, M.D., Ph.D.
Primary Affiliation:
Scientific Director of Biocenter Oulu
Title of the FIMM-Specific Research Project:
Abstract:
The extracellular matrix (ECM) has a crucial role in controlling cell differentiation and function in multicellular animals. It is continually remodelled and synthesised by cells in response to environmental factors such as physical force, hypoxia, trauma and infection. Collagens play a dominant structural role in maintaining the integrity of tissues. However, compelling evidence shows that collagens can also serve as a reservoir for growth factors and can modulate cell signalling critical for tissue morphogenesis and homeostasis. Among the 29 collagens described in vertebrates, only a few are conserved among mammals.
This research group addresses the roles of the pericellular environment in supporting cell growth and differentiation. Of particular interest are collagen XVIII and its several biologically active domains, including an anti-angiogenic domain termed endostatin, a Wnt-binding motif and heparan sulphate glycosaminoglycan side chains, and the homologous collagen XV. Another interesting collagen family is comprised of transmembrane collagens, which can occur both as membrane-bound molecules with signalling properties and shed matrix molecules with distinct properties. Altogether, it appears that the conserved collagens are complex multidomain proteins with not only structural functions but also important regulatory roles in organogenesis and tissue stability. The group works to define their so far poorly known physiological roles and the molecular pathways involving these collagens and their active fragments.
The FIMM-project addresses the hypothesis that the conserved collagens influence epithelial-mesenchymal transformation and other processes in the tumor microenvironment. We will perform bioinformatics analyses in collaboration with Olli Kallioniemi´s group (FIMM) to identify tumor associations and validate the in silico findings by screening selected human tumor materials in collaboration with Helena Autio-Harmainen, Marja-Riitta Väisänen and Timo Väisänen (University of Oulu) and other scientists with suitable clinical materials. To indentify mechanisms underlying the observed ECM-tumor associations in the patient samples, the studies will be complemented with experiments using animal models. Regulatory networks where the conserved collagens participate in will also be identified by using the high-through-put approaches available at FIMM for screening regulatory molecules in cultured cells. Furthermore, the project involves the development of antibodies suitable for screening of large series of fixed human tissue materials and assays for the measurement of ECM molecules of interest in bodily fluids. Altogether, the FIMM project forms a translational pathway including target identification and validation with respect to diagnostic, prognostic and therapeutic value, and development of disease-specific assays and eventually practical applications.
Contact Information
Scientific Director of Biocenter Oulu
P.O. Box 5000
FIN-90014 University of Oulu
Finland
Tel. +358-8-537 6100 and +358-8-537 5800
Fax. +358-8-537 6115
Research group page: