Zsolt Urban, Ph.D.
Assistant Professor
Pediatrics
Genetics
Human and Statistical Genetics Program
Molecular Cell Biology Program
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Office Phone: 314-286-2973
Lab Phone: 314-286-2507
Other Phone:
FAX: 314-286-2893
Box: 8208
Lab Address: 4110 McDonnell Pediatric Research Building
Email: urban_z@wustl.edu
Website: http://peds.wustl.edu/faculty/Urban_Zsolt/
Keywords: cell signaling; development; extracellular matrix; gene expression; genetics
Short Research Description: Human genetic diseases of the elastic fiber system. |
Research Abstract:
Our research group is interested in inherited vascular and connective tissue diseases, particularly in conditions caused by mutations in components of the elastic fiber system. For example, mutations in the elastin gene cause supravalvular aortic stenosis (SVAS), an obstructive arterial disorder characterized by segmental narrowing of major arteries. SVAS occurs as a part of a complex developmental disease, Williams-Beuren syndrome (WBS). We investigate modifying factors of cardiovascular manifestations in WBS. Elastin gene mutations may also cause cutis laxa, a disease characterized by redundant and inelastic skin, emphysema and aortic aneurysm. We use clinical, biochemical, cellular, and animal model studies to understand the distinct disease mechanisms leading to either SVAS or cutis laxa. Furthermore, because cutis laxa is characterized by considerable genetic heterogeneity, we have begun to search for novel cutis laxa genes. As a result, we have discovered that mutations in fibulin-4 cause a novel recessive cutis laxa syndrome characterized by vascular tortuosity, developmental emphysema and severe connective tissue disease. We currently investigate the role of the fibulin family of proteins in vascular and connective tissue development using zebrafish as a model. We apply the knowledge learnt from these studies to uncover genetic risk factors common vascular, pulmonary, and connective tissue diseases. These translational studies presently focus on chronic obstructive pulmonary disease. |
Selected Publications:
Hucthagowder V, Morava E, Kornak U, et al. Loss-of-function mutations in ATPV0A2 impair vesicular trafficking, tropoelastin secretion, and cell survival. Hum Mol Genet 2009 18:2149-2165.
Pober BR, Johnson MC, Urban Z. Mechanisms and treatment of cardiovascular disease in Williams-Beuren syndrome. J Clin Invest 2008 118:1606-1615.
Kornak U, Reynders E, Dimopoulou A, et al. Mutations in the a2 subunit of the v-type H+-ATPase Impair Glycosylation in the Golgi-Apparatus and Cause Autosomal Recessive Cutis Laxa Type II. Nat Genet 2008 40:32-34.
Urban Z, Agapova O, Hucthagowder V, et al. Population differences in elastin maturation in optic nerve head tissue and astrocytes. Invest Ophthalmol Vis Sci 2007 48:3209-3215.
Hucthagowder V, Sausgruber N, Kim KH, Angle B, Marmorstein LY, Urban Z. Fibulin-4: A novel gene for an autosomal recessive cutis laxa syndrome. Am J Hum Genet 2006 78:1075-1080. |