Research in our laboratory is generally focused on understanding the molecular basis of development. One of our primary focuses is on understanding the role of heparan sulfate proteoglycans in the control of cellular responses to components of the extracellular space during development.
Heparan sulfate proteoglycans represent a unique class of developmentally regulated glycoproteins which bind to and regulate a wide range of extracellular proteins including growth factors and their binding proteins, structural extracellular matrix proteins, proteases, and protease inhibitors.
Glypican-3 encodes a cell surface heparan sulfate proteoglycan expressed widely during vertebrate development. Loss of function mutations in the glypican-3 gene in humans causes Simpson Golabi Behmel syndrome (SGBS), a disorder associated with both pre- and postnatal overgrowth, a predisposition to certain childhood cancers, and a complex assortment of congenital defects including skeletal abnormalities.
Mice bearing a targeted deletion in the glypican-3 gene show overgrowth and a similar pattern of malformation as do humans with SGBS, and specifically appear to have defects in skeletal growth and development resulting from defects in both BMP signaling and the function of metalloproteinases in the extracellular space. Understanding the molecular basis of these functions is another primary focus of the laboratory.
Scott Saunders, M.D. Ph.D.
Washington University School of Medicine
Department of Pediatrics
660 South Euclid Ave.
Campus Box 8208
St. Louis, MO 63110