DESCRIPTION 3 OVERALL PROGRAM 3 PROJECT AND CORE SUMMARIES OF DISCUSSION 5 VERTEBRATE ANIMALS 7 INDIVIDUAL PROJECTS AND CORES 8 PROJECT 1: Identification of Self-renewal Pathways in Cancer Stem Cells and Development of Therapeutic Pharmacological Interventions 8 PROJECT 2: Therapeutic Targeting of CD47 on Human Leukemia and Other Cancer Stem Cells...............................................................................................................................15 PROJECT 3: Microfluidic techniques for the molecular and functional analysis of gene expression, chromatin structure, and for in vitro culturing of cancer stem cells 21 CORE A: Bioinformatics Core 27 CORE B: Flow Cytometry Core 28 CORE C: Animal Core 30 CORE D: Administrative Core 32 COMMITTEE BUDGET RECOMMENDATIONS 35 SPECIAL EMPHASIS PANEL ROSTER DESCRIPTION (provided by applicant): This program project grant in response to RFA-CA-08-020 is entitled "Tumor Stem Cells in Cancer Biology, Prevention, and Therapy." Recent evidence suggests that cancers have a cellular hierarchy in which a minority population of cancer cells, called cancer stem cells, drives the growth and spread of a tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the identification of pathways that regulate their growth, metastasis and survival in patients. Targeting the pathways involved in essential processes such as self renewal may lead to more effective therapies. This proposal is an interlocking set of projects designed to identify new cancer stem cell therapeutic targets against breast cancer and leukemia stem cells and to test drugs against some of these targets in a preclinical cancer stem cell model. The three projects of our Program are listed below. Project 1: Identification of self-renewal pathways in breast cancer stem cells and development of therapeutic pharmacological interventions. PI Mike Clarke, Stanford University. Project 2: Therapeutic targeting of CD47 on human leukemia and other cancer stem cells PI, Irv Weissman, Stanford University. Project 3: Microfluidic techniques for the molecular and functional analysis of gene expression, chromatin structure and in vitro culturing of cancer stem cells. PI Steve Quake, Stanford University. These projects are highly interconnected and reliant on each other for the success of the individual project as well as the success of this program. Each project will be supported by 4 cores: an administrative core, a bioinformatics core, an animal model core, and a flow cytometry core.