Molecular and Cellular Mechanisms of Vascular Anomalies

Harvard University (Medical School), Boston MA

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] This supplemental application is a request to support a Genetic Core within the funded Program Project [unreadable] P01 AR048564-01A1, entitled "Molecular and Cellular Mechanisms of Vascular Anomalies". The Program [unreadable] 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 hemangiomas, 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. [unreadable] [unreadable] In three research Projects the investigators are examining and testing the hypothesis 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, they are also attempting to identify genes responsible for rare cases of inherited hemangiomas and to establish mouse models allowing further studies of detailed pathological mechanisms. Finally, they are generating mouse models for venous and glomuvenous malformations, characterizing the cellular and molecular consequences of the causative mutations, and searching for mutations in additional families. The Genetics Core will provide all projects, but particularly Projects 1 and 3, with DNA, RNA, protein and tissue samples as well as lymphoblasts and hemangioma-derived cells and clinico-genetic information. The proposed Core, based on the extensive clinical-genetic expertise of the Program investigators in Brussels, is the primary Program site for collection and storage of data and samples for studies of familial forms of hemangiomas and vascular malformations. Without such data and samples, collected on the basis of human studies protocols that have been approved both by Harvard Medical School and Catholique University of Louvain, a major portion of the research in Project 1 (in Boston) and Project 3 (in Brussels) cannot be accomplished. [unreadable] [unreadable] [unreadable]