Areas of Focus
Early blood and lymphatic vascular development and vascular anomalies.
The process of cardiovascular and lymphatic vascular development is critical for fetal development. Our group focuses on angio- and lymphagiogenic signaling pathways that drive these processes using genetic mouse models. We study fetal abnormalities associated aneuploidies that result in vascular defects and contribute to nuchal edema. As part of a collaborative research group with Dr. June Wu (Plastic Surgery), we study the causes of vascular anomalies, such as infantile hemangioma and lymphatic malformations. These studies focus on the stem cell origin of these diseases.
We have identified key roles for the VEGF/VEGF-Receptor and Notch signaling pathways in ovarian, uterine and placental angiogenesis. Using mouse models we probe angiogenic factor function in folliculogenesis, corpus luteum formation, and uterine function to understand normal fertility. New studies have been initiated to address a role for macrophages and inflammatory cytokines in reproductive organs.
Cervical remodeling during pregnancy
Successful pregnancy depends on proper cervical function and remodeling during delivery, a process driven by matrix metallo-proteinases (MMPs) that act on extracellular matrix components (ECM). Our group uses mutant mice deficient in MMPs and Anthrax Toxin Receptors to understand ECM remodeling of the cervix and uterus during pregnancy. These murine studies complement the work of investigators in the Collaborative Cervical Research Group at Columbia University, which studies cervical structure and dysfunction in preterm birth; including Ron Wapner (OB/GYN), Kristin Myers (Bioengineering)
Gynecological tumors and tumor angiogenesis
Building on the development of novel anti-angiogenic agents, Notch1 decoys, we are evaluating how inhibition of either VEGF and/or Notch can complement other chemotherapeutic agents in the treatment of ovarian cancer and other gynecological malignancies. A recently launched effort uses a systems biology approach to understand the molecular mechanisms of platinum resistance in ovarian cancer.