This CAREER project aims to integrate research and education programs dedicated to the interdisciplinary investigation of functional interactions between hypoxic pathways and matrix-driven cues that are essential for vascular morphogenesis and network assembly. The proposed research is based on an interdisciplinary approach to the study and basic understanding of vascular network assembly and requires a particular knowledge set, covering stem cell and vascular biology, as well as engineering fundamentals. The proposed research promises both to uncover the mechanisms underlying vasculature growth and to elucidate the interfaces involved in vascular development signaling pathways for vascular regeneration applications.
Early in development and during ischemic disorders, the passive diffusion of oxygen and nutrients becomes limiting; responses to decreased oxygen levels, or hypoxia, are required for the normal development of the vascular system or vascular regeneration. Additionally, the three dimensional cellular environment function as a physical anchor and generates a number of extrinsic factors that control vascular assembly. The differentiation of human embryonic stem cells has been shown to recapitulate aspects of early embryogenesis in sequential stages, hence providing a tool to explore molecular events that take place during human vascular development and, most likely, vascular growth in adulthood. The objectives of the research plan are: (1) to determine vascular progenitor responses to hypoxia; (2) To analyze the network assembly of vascular derivatives in hydrogels; and (3) To examine the hypoxic network assembly of vascular derivatives in hydrogels.
The research will be complemented by integrated educational and outreach activities that promote teaching and learning across minority and under-represented groups. For high school and undergraduate students, it could initiate an interest in the fields of stem cell engineering and regenerative medicine through hands-on and laboratory learning. It will expose international students to fields in which they currently receive no education. Finally, as engineering is not introduced in many public school curriculums until high school, the Science, Technology, Engineering and Math (STEM) mentorship program will expose inner city school students to activities they otherwise might not experience and may spark their interest in science while providing them with opportunities for academic success.
