 Oncogenesis;2) Cell Cycle, Cytoskeleton and Genomic Stability;and 3) Epithelial Neoplasia (including skin, prostate and lung cancer subgroups). Investigations are focused on mechanistic studies of oncogenes and tumor suppressor genes, the control of cell division, genomic stability and DNA damage checkpoints, as well as disease-specific interests in hematologic malignancies, skin, prostate and lung cancers. The 40 investigators represent two different schools (the School of Medicine and the School of Humanities &Sciences), 16 Departments, and five Divisions within the Department of Medicine. The research activities of the 40 investigators are supported by 73 peer-reviewed, investigator-initiated grants (R01s and others), and five T32 training awards. Total NCI support is $4.3 million, other NIH support is $7.2 million, and non-NIH support is $3.2 million. Since 2005, program investigators have published over 400 manuscripts relevant to cancer biology in peer-reviewed journals. The Cancer Center will continue to be invaluable in assisting with the translation of the basic science findings from this Program into new clinical approaches for the diagnosis and treatment of patients with cancer.

The goal of the proposed research is to understand the mechanisms of how genes are regulated in different tissues. This will be accomplished through the study of the human gene encoding debranching enzyme and molecular analysis of Type III glycogen storage disease. In this disease there are patients who lack debranching enzyme activity in both liver and muscle, and patients with enzyme deficiency confined to liver; yet the enzyme is a monomeric protein and appears to be identical in all tissues. The proposed research hypothesizes that debranching enzyme in liver and muscle is encoded by a single gene; its expression, however, is under separate genetic control. Patients with various clinical and enzymatic subgroups of Type III glycogen storage disease are being followed at Duke Medical Center; fibroblasts from these patients h