Marion K. Gordon
Department of Pharmacology and Toxicology
Piscataway, NJ 08854-8020
Cell-matrix interactions; cel,. developmental and molecular biology of extracellular matrix molecules
Another major project examines how extracellular matrix molecules establish the architecture of our tissues and organs during development and in pathology. A subset of collagens, the fibril-associated collagens (FACITs), modulate the properties of collagen fibrils, altering how the fibrils interact with adjacent fibrils. One of the lab's major goals is to understand the role of these bridging molecules in proper tissue architecture. In the developing eye, the cornea is at first opaque, and undergoes a compaction event that results in a transparent cornea. Dr. Gordon's work suggests that the FACIT molecule collagen XIV facilitates the compaction event by preventing the fusion of collagen fibrils. This would maintain fibrils in a lattice that can transmit light.
Misregulation of EMMPRIN and/or FACIT collagens is hypothesized to be important in disease states involving inappropriate synthesis and degradation of extracellular matrix. The laboratory is also investigating the involvement of collagens and EMMPRIN in the premature rupture of fetal membranes, in pulmonary hypertension, as well as in pulmonary and hepatic fibrosis. In each of these pathologies, FACIT collagen XII appears to temporarily stabilize new fibril structures until a permanent stabilization occurs, and a concomitant decrease in FACIT collagen XIV appears to allow type I collagen fibril fusions. Such fusions impair the resiliency of the tissues. Future work will examine the FACIT collagens in cystic fibrosis.