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 are currently investigating modifying factors of cardiovascular manifestations in WBS. Elastin gene mutations may also cutis laxa, a disease characterized by redundant and inelastic skin, emphysema and aortic aneurysm. We are using 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 are currently investigating the role of the fibulin family of proteins in vascular and connective tissue development by using zebrafish as a model. In the long term, we intend apply the knowledge learnt from these studies to uncover genetic risk factors common vascular, pulmonary, and connective tissue diseases. |
Selected Publications:
Hu Q, Loeys BL, Coucke PJ, De Paepe A, Mecham RP, Choi J, Davis EC, Urban Z. Fibulin-5 mutations: Mechanisms of impaired elastic fiber formation in recessive cutis laxa. Hum Mol Genet (in press).
Hu Q, Reymond JL. Pinel N, Zabot MT, Urban Z. Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes. J Invest Dermatol 2006 126:283-290.
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.
Szabo Z, Crepeau MW, Mitchell AL, Stephan MJ, Puntel RA, Loke KY, Kirk RC, Urban Z. Aortic aneurysmal disease and cutis laxa caused by defects in the elastin gene. J Med Genet 2006 43:255-258.
Ruigrok Y, Seitz U, Wolterink S, Wijmenga C, Rinkel G, Urban Z. Association of polymorphisms and haplotypes in the elastin gene in Dutch patients with sporadic aneurysmal subarachnoid hemorrhage. Stroke 2004 35:2064-2068. |