12.0 Abstract: Molecular and Structural Biology (MSB) Program The MSB Program is a highly innovative basic science research program at the University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC) that aims to bring new agents to the clinic. MSB members study mechanistic cancer-relevant questions at the cellular and molecular level and use these discoveries to design novel cancer therapeutic strategies and drug candidates. These agents are then available for testing in the clinical programs (ET, HRC, TII). MSB work is focused in three areas: Aim 1, Define mechanisms of genomic instability in cancer, investigates sources of genomic instability due to DNA damage and/or loss of DNA repair capabilities in cancer and validating actionable therapeutic targets to develop new clinical approaches that take advantage of such genomic instability for treating cancer. Aim 2, Identify changes in gene expression and RNA function in cancer, focuses on therapeutic targeting of translation initiation, RNA biology, and gene expression processes that are co-opted by cancer cells to drive tumor growth and/or metastasis. Aim 3, Define how signaling pathways in cancer are deregulated, seeks to understand how cancer cell signaling can be used to target cancer cells, including developing strategies to inhibit oncogenic and/or cancer stem cell-specific pathways and/or to restore tumor suppression functions. To achieve these aims, MSB members are supported by extensive expertise available in other UMGCCC programs in translating basic research findings to the clinic, and by availability of exceptional shared services. The 47 members of the MSB Program include 34 full members and 13 associate members who conduct cancer-focused research supported by $9.6 million annual direct cost funding ($13.2 million total), including $1.2 million (12.5%) from NCI and $7.5 million from other peer-reviewed sources. MSB members receive $0.83 million annually from non–peer-reviewed funding sources. During this funding period, MSB members authored 455 cancer-related publications, of which 13% resulted from intraprogrammatic, 20% from interprogrammatic, and 2% from intra and interprogrammatic collaborations. A high percentage of publications (58%) are with external investigators, reflecting the high national impact of the MSB Program and 13% of publications are in journals with an impact factor ≥10. The MSB Program collaborates with other UMGCCC research programs and engages Community Outreach and Engagement as a bridge to identify cancer research priorities of our community in the catchment area.