Cerebral Blood Vessel Development & Stroke

Notch signaling is required during normal mammalian vascular development and vessel maturation. Mutations in the Notch ligand JAGGED1 cause 94% of Alagille syndrome (ALGS) cases, a haploinsufficient developmental disorder, originally termed Arteriohepatic Dysplasia for its underlying vasculopathies. Although ALGS is known as a multisystem disorder involving liver, heart, eyes, face and skeleton, there is also a recognized complication of intracranial bleeding resulting in 25% mortality.

During development, cerebral vessels graduate into a functional collateral circle termed the “Circle of Willis” through stages of cell birth, differentiation, vasculogenesis, and angiogenesis. Insults during this complex generation and after sepsis suggest an increased propensity towards stroke in both gray and white matter of the brain and spinal cord and have implications towards the realization of adequate recovery and regeneration.

Our goal is to elucidate the molecular and cellular mechanisms during vascular development within the central nervous system and how this may relate to various human genetic states. We use a variety of techniques including transgenic mice, in vitro and ex vivo immunohistochemistry, real-time surgical imaging, and advanced neuroimaging techniques.

Collaborators:

Stacey Huppert , Basilia Zingarelli, Hector Wong, Blaise Jones, Jun Goto, Kenneth Campbell, Neuroimaging Research Core