The surfaces of cells are covered with a dense layer (glycocalyx) of glycoproteins, glycolipids, and proteoglycans. These glycoconjugates bind to various proteins, including growth factors, enzymes, and extracellular matrix proteins, and thereby participate in a wide variety of biological phenomena related to cell differentiation, proliferation and migration, morphogenesis, and normal and pathophysiology. To a large extent these interactions are determined by the structure of the polysaccharide chains (glycans) that distinguish the various subclasses of glycoconjugates. The assembly of these molecules involves many enzymes, substrates and cofactors and differs from the assembly of nucleic acids and proteins in not requiring a template. Understanding how cells organize the assembly process to bring about cell-type specific glycans and biological responses is a major problem in modern cell biology.
Research in my lab utilizes a combination of chemistry, cell biology and genetics to understand the structure and function of sulfated glycosaminoglycans found on proteoglycans. This group of glycans consists of heparan sulfate and chondroitin/dermatan sulfate. We have numerous cell and organismal mutants altered in genes that encode the biosynthetic enzymes and the protein cores on which the chains assemble. Studies of these cell lines and mice bearing conditional and systemic mutations allow us to analyze glycan function in normal physiology and disease. Current work arranged by systems include:
The lab currently consists of 2 project scientists, 7 postdocs/fellows, 3 graduate/research assistants, 2 technicians, and 2 undergraduate. We have lab meeting every week (Wednesdays at 9:30 am), a journal club focused on Current Literature in Glycobiology (BIOM 246, Fridays at noon), and periodic submeetings to coordinate projects with collaborators on and off campus. Trainees receive classical training in the chemistry and biochemistry of glycans and modern training in genetics, cell biology and physiology. My door is always open, so stop by anytime.