Peter H. Byers, M.D.

Professor of Medicine and Pathology
Adjunct Professor of Genome Sciences
Adjunct Professor of Oral Biology

University of Washington
D-518 Health Sciences Building
Pathology, Box 357470
Seattle, WA 98195

Phone: (206) 543-4206
FAX: (206) 616-1899

Research Program:

Our objectives are to understand the molecular pathogenesis of inherited disorders of connective tissue. We have focused on disorders that affect collagen genes and the enzymes involved in the post-translational modification of collagens. The clinical disorders include varieties of osteogenesis imperfecta, of Ehlers-Danlos syndrome, and of some other disorders of vascular integrity. These disorders result from mutations in the type I collagen genes (COL1A1 and COL1A2), the type III collagen genes (COL3A1), type V collagen genes (COL5A1 and COL5A2), and some additional genes such as those involved in prolyl 3-hydroxylation (CRTAP and LEPRE1), and the TGFB receptor genes (TGFBR1 and TGFBR2). These mutations affect mRNA processing and transport, protein assembly and folding, molecular transport within the cell, and molecular processing and fibril aggregation in the extracellular matrix. We are trying to understand the mechanisms by which the cell recognizes and adapts to mutations that affect splicing, chain assembly and molecular transport as well as to define the manner in which mutations produce the phenotypes. The strategies to reach these goals include the analysis of the normal and altered order of splicing in complex genes, isolation of procollagen binding proteins by direct immunoprecipitation of bound proteins, analysis of pathways of intracellular degradation, and analysis of changes in gene expression within cells that harbor these mutations.

Representative Publications: