My long-term goal is to understand molecular mechanisms of cell differentiation and development with particular emphasis on vasculogenesis and angiogenesis. Major effort has been made to discover genes that play critical roles in cell differentiation and development. Although this "gene hunting" effort has been paying off recently, there is major pit-fall in this type of approach. We have invented a new version of "protein-trap" approach, which enables us to discover proteins that escape the hunting effort made by any of the currently used gene-discovery methods. Furthermore, we expect to gain novel mechanistic insights into the processes of cell differentiation and development including vasculogenesis and angiogenesis based on the discovery made by this protein-type approach. This is a R21 application to request for the two year funding that enables us to use this novel approach to discover key proteins in cell differentiation and development. Initially, we will focus on proteins expressed during vasculogenesis and/or angiogenesis. However, our goal is not limited to these classes of proteins. We are also broadly interested in other classes of proteins that play key roles in cell differentiation and development in general. We expect that this two-year funding will enable us to make the initial discovery. This initial discovery is expected to form a basis for us to move on to more functional and mechanistic studies that could be funded through R01 mechanism following the completion of this project. We expect our discovery has immediately impact on the invention of novel and effective therapeutics targeted to many clinical areas including cancer, stem cell based regenerative medicine and cardiovascular diseases.