This Program Project, entitled '""""""""Molecular and Cellular Mechanisms of Vascular Anomalies,"""""""" represents the concerted and collaborative efforts of three research groups, two in Boston and one in Brussels, Belgium, to elucidate the causes and abnormal mechanisms that are responsible for vascular anomalies in the skin. Commonly called birthmarks, these anomalies include infantile hemangioma, a vascular tumor found in 5-10% of Caucasian children at 1 year of age, and vascular malformations. Hemangiomas usually appear a few days after birth, grow rapidly for a few weeks to months, and then slowly regress over a 5-10 year period. In most cases, no treatment is needed, but sometimes vital, structures can be obstructed or distorted causing serious problems. In contrast to hemangiomas, malformations do not regress, but grow with the child, and can become life-threatening. The investigators have recently found that hemangiomas contain clonal expansions of abnormal endothelial cells, and they have discovered two types of mutations that cause localized abnormalities in the skin of patients with venous malformations and glomuvenous malformations. In three research Projects, supported by three Cores, the Program investigators propose to examine and test the hypotheses that hemangiomas result from somatic mutations in genes that control endothelial cell proliferation and/or maturation from precursor cells, causing rapid growth of abnormal capillaries. In addition to identifying such genes and mutations, it is also proposed to identify genes responsible for rare cases of inherited hemangiomas and to establish mouse models allowing further studies of detailed pathological mechanisms. Finally, they now propose to generate mouse models for venous and glomuvenous malformations, characterize the cellular and molecular consequences of the causative mutations, and search for mutations in additional families. The proposed studies should lead to a better understanding of the pathogenesis of hemangiomas and malformations and therefore a basis for development of effective therapies. In addition, a better understanding of the causes and mechanisms of vascular anomalies will provide novel insights into blood vessel formation and growth. This will add significantly to the efforts to develop novel antiangiogenic therapies for cancer, diabetic retinopathy, and rheumatoid arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Program Projects (P01)
Project #
5P01AR048564-02
Application #
6800722
Study Section
Special Emphasis Panel (ZAR1-RJB-B (M1))
Program Officer
Moshell, Alan N
Project Start
2003-09-15
Project End
2008-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$1,050,476
Indirect Cost
Name
Harvard University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115
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