This Gordon Research Conference will focus on integrating current knowledge concerning the regulation of self renewal of normal stem cells and how this process is disrupted in cancer. Stem cells play a critical role in normal development and a myriad of human diseases. Recent evidence has implicated stem cells in processes such as aging, cancer and hereditary diseases organs such as the gut, skin, brain and blood. In addition, understanding the process by which stem cells regenerate themselves holds promise for cell therapy for diseases such as diabetes, stroke, heart attacks, cancer, hereditary and acquired muscular dystrophy, spinal chord injury, and birth defects including cranial-facial defects. Finally, this GRC on Stem Cells and Cancer has relevance to bioterrorism. One of the most feared weapons that might be used in bioterrorism is an attack using radiation, either as a nuclear bomb or with a device used to spread radioactive material in a population center. The primary cause of death from exposure to radiation is toxicity to the stem cells of the blood, gut and brain. If a person survives the immediate toxicity to stem cells, then there is a high risk of cancer developing because of the genetic damage to the stem cell compartment. Six specific aims are proposed: 1. To explore the molecular mechanisms that regulate normal stem cell self renewal and the role that oncogenes play in this process. 2. To explore how cancer cell self renewal differs from that of normal stem cells. 3. To discuss the organization of the developmental hierarchy of normal cells in organs in which common cancers arise will be examined as well as the identity of the specific cell type(s) in a particular tissue that gives rise to cancer/leukemia cells. 4. To explore the notion that cancers of the blood and solid tumors may contain a cellular hierarchy where not all of the cancer cells can self renew. 5. To present the latest research investigating the interaction of cancer cells with normal stromal cell components of the tumor. 6. To discuss emerging strategies to develop therapies specifically targeting self renewing cancer cells. [unreadable] [unreadable] [unreadable] [unreadable]