Research Projects in Medical Sciences

Molecular and Cellular Mechanisms of Vascular Anomalies

Faculty: Bjorn R. Olsen, MD, PhD
Funder(s): NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases

This program project (P01) aims to elucidate pathogenetic mechanisms of human vascular anomalies, to generate mouse models and identify therapeutic targets. These common vascular disorders belong to the group of childhood conditions popularly known as vascular birthmarks. One in about 100 children born have a vascular birthmark, and although significant progress has been made in identifying the genetic basis for many of the more rare forms of these anomalies, they are frequently misdiagnosed and effective therapies are unavailable. Hemangiomas usually appear a few days after birth, grow rapidly for a few weeks to months, and then slowly regress over a five- to 10-year period. Malformations do not regress, but grow with the child and can become life threatening.

Building on discoveries made during a previous grant period and taking advantage of exceptional patient-data, tissue, cell, and nucleic-acid resources that have been collected in two cores-one in Boston and one in Brussels-the investigators plan to use genetic, cell-biological, and protein-chemistry techniques to gain deeper understanding of how gene mutations that are associated with hemangioma and venous malformations affect endothelial and smooth muscle cell differentiation and function. Animal models comprising human cells transplanted into immunocompromised mice and genetically modified mice carrying hemangioma and venous malformation-associated mutations will be characterized and used for testing hypotheses and explored for preclinical trials of disease-modifying drugs.

Please visit the Vascular Anomalies Program Project website for more information about this study. Read an article about the study, “Genetic Switch Found for Growth of Common Childhood Tumor,” in Focus, the newsletter of HMS, HSDM, and HSPH.