Senior Vice Chancellor's Research Seminar

Topic Overview:

Elastic fibers are extracellular matrix structures of remarkable longevity but limited regeneration potential. Urban’s lab studies rare, inherited disorders of the elastic fibers to identify molecules and pathways essential for the formation, maintenance, and function of these structures. A combination of human genetic, biochemical, cell biological, and animal studies using zebrafish as a model have provided the following key molecular insights:

1. Elastic fiber formation is a complex, hierarchical, cell-mediated process that requires secreted multiadhesive proteins (FBLN4, FBLN5, LTBP4) to facilitate the correct deposition of an elastin polymer onto a fibrillin microfibril template.

2. Specific proteins (ATP6V0A2, ATP7A, RIN2, GORAB) within the secretory pathway, particularly the Golgi apparatus, are required for the efficient sorting, secretion and cross-linking of elastic fiber components.

3. Biosynthetic and transport proteins (PYCR1, ALDH18A1, SLC2A10) associated with the mitochondria are necessary for correct elastic fiber function.

4. Mutations in genes responsible for the production of proteins in any of the three compartments listed above result in the dysregulation of transforming growth factor-beta signaling, contributing to disease.

Taken together, these studies highlight the intricate connections among membrane trafficking, metabolism, extracellular matrix assembly, and growth factor signaling and identify new molecular targets for the treatment of rare, inherited, and common complex disorders of the elastic fibers.





		Topic Overview: Elastic fibers are extracellular matrix structures of remarkable longevity but limited regeneration potential. Urban’s lab studies rare, inherited disorders of the elastic fibers to identify molecules and pathways essential for the formation, maintenance, and function of these structures. A combination of human genetic, biochemical, cell biological, and animal studies using zebrafish as a model have provided the following key molecular insights: 1. Elastic fiber formation is a complex, hierarchical, cell-mediated process that requires secreted multiadhesive proteins (FBLN4, FBLN5, LTBP4) to facilitate the correct deposition of an elastin polymer onto a fibrillin microfibril template. 2. Specific proteins (ATP6V0A2, ATP7A, RIN2, GORAB) within the secretory pathway, particularly the Golgi apparatus, are required for the efficient sorting, secretion and cross-linking of elastic fiber components. 3. Biosynthetic and transport proteins (PYCR1, ALDH18A1, SLC2A10) associated with the mitochondria are necessary for correct elastic fiber function. 4. Mutations in genes responsible for the production of proteins in any of the three compartments listed above result in the dysregulation of transforming growth factor-beta signaling, contributing to disease. Taken together, these studies highlight the intricate connections among membrane trafficking, metabolism, extracellular matrix assembly, and growth factor signaling and identify new molecular targets for the treatment of rare, inherited, and common complex disorders of the elastic fibers.