Development funds for the current Cancer Center Support Grant (CCSG) funding period have been used to support ten new investigators for up to three years following their arrival. Six of the ten have established well funded research programs and have had a strong impact on the Cancer Center and their research programs. In this proposal we are requesting funds to support two new faculty annually and propose to use CCSG funds to support each of them for one year; the remainder of their startup support being provided by The Wistar Institute. The current planning effort has identified the need to recruit 12-18 new junior and mid-level faculty overall over the next five years and will devote over $10 million of Institute funds for this effort. We intend to direct our faculty recruitment and program development toward: Application of systems biology to relate genetic alterations to biological features of cancer cells; Further development of our understanding of basic mechanisms of gene control; Application of organotypic and other advanced model systems to understand the effect of cellular interactions in cancer; Use of the understanding of mouse genetics and animal model systems to explore the effect of one or more genes in a whole animal system; Use of stem cells to understand the mechanisms and relationship of patterns of gene expression in vertebrate development programs; and Expansion of our vaccine effort and identification of molecules that can promote the effector arm of the immune system. The Cancer Center has identified space and financial resources to achieve these goals, and the success of this plan will be enhanced by the availability of CCSG funds.