Grants We Funded

Abstract
This project aims to understand the role of Notch signaling in the regulation of the lifecycle of infantile
hemangioma (IH) from proliferation through involution. IHs are the most common benign tumor of infancy,
yet its pathogenesis is still poorly understood, and there is no FDA-approved therapy for the treatment of
IHs. Most His develop in isolation and never require intervention. However, problematic hemangiomas can
cause major morbidity including amblyopia, permanent disfiguring scarring, and even mortality. In addition, in
PHACE syndrome, a large, segmental IH is associated with major abnormal vascular architecture, and
affected infants have missing blood vessels and circulation to the brain, increasing their risk of strokes.
Notch signaling plays a pivotal role in cell fate determination and cellular differentiation during
embryogenesis. Notch genes have been shown to be expressed in IHs. Since there are no viable animal models for the study of IHs, this project will use isolated hemangioma stem cells (HemSCs) and hemangioma endothelial cells (HemECs) to study Notch signaling. Using silencing RNA (siRNA) technology, expression of specific Notch genes will be inhibited in order to study the function of
these isolated HemSCs and HemECs. Other methods include using commercially available pan-Notch
inhibitors such as gamma-secretase, as well as specifically designed antibodies produced in our laboratory.
Cellular function such as proliferation, migration, and endothelial network formation will be studied. In
particular, preliminary results in our laboratory has shown that human umbilical venous endothelial cells
(HUVECs), when co-cultured with HemSCs, results in a more complex vascular pattern, with thicker tubular
structures, and increased branching points.
Understanding specific regulators of IHs will help in the design of a specific treatment for affected infants.
Moreover, it will provide insight into vasculogenesis--the formation of blood vessels from stem cells. This
knowledge will have broad applications, including the design of vascularized, tissue-engineered products.

Biography
Dr. June Wu is an Assistant Professor of Surgery at the College of Physicians and Surgeons, Columbia University Medical Center. Her clinical interests are craniofacial surgery and vascular anomalies. Her research focuses on the pathophysiology of hemangiomas. In particular, she is interested in exploring the role of Notch signaling in the pathogenesis and evolution of hemangiomas. Her laboratory first showed that Notch genes are expressed in hemangiomas, and current work investigates the effects of Notch receptor and Notch ligand interactions. After finishing her undergraduate studies at Princeton University, she enrolled at Columbia’s College of Physicians & Surgeons. She was inspired to go into plastic surgery by her first mentor, Dr. David Chiu. She trained at the Integrated Plastic Surgery program at Montefiore Medical Center under Dr. Berish Strauch. Her craniofacial and vascular anomalies fellowships were done at Children’s Hospital Boston under Dr. John Mulliken.