Kusche-Gullberg Lab
Heparan sulfate proteoglycans (HSPGs), composed of a sulfated polysaccharide (heparan sulfate) chains attached to a core protein, play important roles in regulating communication between in- and outside of the cells as well as between cells As co-receptors for numerous signaling molecules HSPGs modify cell behavior and regulate cell growth both in normal and diseased tissues. Our primary aim is to understand the molecular regulation of HSPG synthesis and how this influences cell behavior.
Specifically, we study the molecular mechanisms by which the EXT-family of influences HSPG structure and cell-stroma interactions. Mutations in EXT1 or EXT2 result in multiple osteochondromas (exostoses) and predispose to the development of chondrosarcoma. We have recently shown that changes in the levels of the EXT-proteins are important for HSPG-regulated growth factor binding and signaling. Together with EXT1 and EXT2, three additional family members, designated EXTL1, EXTL2, and EXTL3, are suggested to be involved in HSPG formation. The EXT1 and EXT2 genes are thought to be classical tumor suppressor genes whereas the roles of EXTL genes in cancer development are unclear.
In addition, we study the role of HSPG in evolution using the sea anemone Nematostella system.