The applicant's goal is to become an independent clinician scientist who engages in basic research that has clinical relevance. The applicant has obtained both clinical and research training to prepare her for a career in medical research. She is interested in studying the development of the lung vasculature, since it not only addresses questions on fundamental developmental processes but may also provide insights into the pathogenesis of diseases in which abnormal vascular development is a component, such as cancer, vascular malformations, pulmonary hypertension, chronic inflammation, and abnormal lung repair following injury. The lung is one of the most highly vascularized tissues in the body, yet the mechanisms regulating the development of the pulmonary vasculature has been poorly characterized. The current application focuses on lung vascular development in the early embryonic period. The hypothesis is that epithelial-mesenchymal interactions are important for the coordination between airway and vessel development, and he propose to study the molecular mechanisms of these interactions during early mouse embryonic development. Specifically, her will (1) define the processes of lung vascularization during early mouse embryonic development and characterize the temporal and spatial relationship between vessel and airway development, (2) identify molecular factors that may function in the development of the embryonic lung vasculature, and (3) determine the specific roles these factors play in the interactions between lung epithelium and mesenchyme that are necessary for vascular development. The applicant's long term goal is to understand the molecular mechanisms regulating lung vessel formation in normal development and in diseases. The current proposed study will add to the knowledge of the development of the lung vasculature during early organogenesis and help establish a firm foundation on which future studies can be based. Besides research, training activities include didactic studies, participation in seminars and conferences, formal presentations at local and national meetings, supervised preparations of manuscripts and grants, and regular meetings with a Scientific Advisory Council. The sponsor and the members of the Scientific Advisory Council have been chosen for their expertise in areas and approaches relevant to the proposed research. In addition, they are senior members of the faculty who will be able to guide the applicant in career development. UCSF is fully committed to the development of junior faculty researchers, and offers an excellent environment for the scientific development of a clinician scientist.
Zhao, Liqing; Wang, Ke; Ferrara, Napoleone et al. (2005) Vascular endothelial growth factor co-ordinates proper development of lung epithelium and vasculature. Mech Dev 122:877-86 |
Vu, Thiennu H; Alemayehu, Yemisrach; Werb, Zena (2003) New insights into saccular development and vascular formation in lung allografts under the renal capsule. Mech Dev 120:305-13 |
Engsig, M T; Chen, Q J; Vu, T H et al. (2000) Matrix metalloproteinase 9 and vascular endothelial growth factor are essential for osteoclast recruitment into developing long bones. J Cell Biol 151:879-89 |
Gerber, H P; Vu, T H; Ryan, A M et al. (1999) VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med 5:623-8 |