Detailed understanding of molecular function in biological systems requires information about the three dimensional structures of macromolecules. The wealth of information available from studies in structural biology provides novel and powerful insights into function. Chemical biology, the modulation of protein function by small molecules, provides both tool compounds to explore biological function as well as leads for development of therapeutic agents. The merging of the structural and chemical biology faculties brings together two groups that speak the same language, the language of molecular structure, making the merger a natural grouping. The Chemical and Structural Biology Program (CSB) defines its overarching goal as the facilitation of this dialogue to accelerate understanding and treatment of cancer. CSB focuses this goal around four thematic elements;(1) Structural and chemical biology targeting transcription factors. (2) Structural and chemical biology targeting signaling molecules, (3) Advancing structural biology technologies, (4) Chemical biology for imaging, detection, and diagnosis. John H. Bushweller, PhD, Professor of Molecular Physiology and Biological Physics, leads the Program with Kevin R. Lynch, Professor of Pharmacology and of Biochemistry and Molecular Genetics. CSB currently comprises 19 Members and 6 Associate Members from seven different departments at the University of Virginia (UVA). By including the Chemistry Department, the Program provides unique, cross-campus opportunities to bring the power of chemistry to bear on cancer. CSB leadership has recruited seven of these individuals to UVA since the last renewal. Total extramural funding for the Program exceeds $11 million, including more than $1.7 million from the National Cancer Institute (NCI) and more than $8.8 million from other National Institutes of Health (NIH) entities. The Program Members rely heavily on Cancer Center-supported infrastructure, particularly the Biomolecular Analysis Facility and NMR instrumentation. Pilot Funds and research retreats have provided the framework for productive collaborations among UVA Cancer Center members. The many activities and interactions of CSB Members have led to 287 publications, of which 29% were inter-programmatic publications and 15% were intra-programmatic publications since the last renewal.

Public Health Relevance

Understanding the structures of proteins, how they become altered in cancer, and how to design drugs that inhibit their altered behavior is key to improvements in cancer treatment and detection, and is the goal of the Chemical and Structural Biology Program.

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Subcommittee G - Education (NCI)
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Meisner, Joshua K; Annex, Brian H; Price, Richard J (2015) Despite normal arteriogenic and angiogenic responses, hind limb perfusion recovery and necrotic and fibroadipose tissue clearance are impaired in matrix metalloproteinase 9-deficient mice. J Vasc Surg 61:1583-94.e1-10
Zarling, Angela L; Obeng, Rebecca C; Desch, A Nicole et al. (2014) MHC-restricted phosphopeptides from insulin receptor substrate-2 and CDC25b offer broad-based immunotherapeutic agents for cancer. Cancer Res 74:6784-95
Henretta, Melissa S; Copeland, Amy R; Kelley, Sarah L et al. (2014) Perceptions of obesity and cancer risk in female bariatric surgery candidates: highlighting the need for physician action for unsuspectingly obese and high risk patients. Gynecol Oncol 133:73-7
Jones, Ryan; Libby, Bruce; Showalter, Shayna L et al. (2014) Dosimetric comparison of (192)Ir high-dose-rate brachytherapy vs. 50 kV x-rays as techniques for breast intraoperative radiation therapy: conceptual development of image-guided intraoperative brachytherapy using a multilumen balloon applicator and in-room Brachytherapy 13:502-7
Santen, Richard J (2014) Menopausal hormone therapy and breast cancer. J Steroid Biochem Mol Biol 142:52-61
Wang, Shaolin; Yang, Zhongli; Ma, Jennie Z et al. (2014) Introduction to deep sequencing and its application to drug addiction research with a focus on rare variants. Mol Neurobiol 49:601-14
Cohen, Jarish N; Tewalt, Eric F; Rouhani, Sherin J et al. (2014) Tolerogenic properties of lymphatic endothelial cells are controlled by the lymph node microenvironment. PLoS One 9:e87740
Newhook, Timothy E; Blais, Edik M; Lindberg, James M et al. (2014) A thirteen-gene expression signature predicts survival of patients with pancreatic cancer and identifies new genes of interest. PLoS One 9:e105631
Hubbard, Matthew A; Khalil, Ashraf A; Schoeff, Stephen S et al. (2014) Nanoimmunoassay to Detect Responses in Head and Neck Cancer: Feasibility in a Mouse Model. Otolaryngol Head Neck Surg 151:92-99
Wang, Chun-Chao; Janes, Kevin A (2014) Non-genetic heterogeneity caused by differential single-cell adhesion. Cell Cycle 13:2149-50

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