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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee G - Education (NCI)
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Wallrabe, Horst; Svindrych, Zdenek; Alam, Shagufta R et al. (2018) Segmented cell analyses to measure redox states of autofluorescent NAD(P)H, FAD & Trp in cancer cells by FLIM. Sci Rep 8:79
Olmez, Inan; Love, Shawn; Xiao, Aizhen et al. (2018) Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha. Neuro Oncol 20:192-202
Wang, T Tiffany; Yang, Jun; Zhang, Yong et al. (2018) IL-2 and IL-15 blockade by BNZ-1, an inhibitor of selective ?-chain cytokines, decreases leukemic T-cell viability. Leukemia :
Yao, Nengliang; Zhu, Xi; Dow, Alan et al. (2018) An exploratory study of networks constructed using access data from an electronic health record. J Interprof Care :1-8
Kiran, Shashi; Dar, Ashraf; Singh, Samarendra K et al. (2018) The Deubiquitinase USP46 Is Essential for Proliferation and Tumor Growth of HPV-Transformed Cancers. Mol Cell 72:823-835.e5
Conaway, Mark R; Petroni, Gina R (2018) The Impact of Early-Phase Trial Design in the Drug Development Process. Clin Cancer Res :
Szlachta, Karol; Kuscu, Cem; Tufan, Turan et al. (2018) CRISPR knockout screening identifies combinatorial drug targets in pancreatic cancer and models cellular drug response. Nat Commun 9:4275
Khalil, Shadi; Delehanty, Lorrie; Grado, Stephen et al. (2018) Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor. J Exp Med 215:661-679
Olmez, Inan; Zhang, Ying; Manigat, Laryssa et al. (2018) Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma. Cancer Res 78:4360-4369
Parini, Paolo; Melhuish, Tiffany A; Wotton, David et al. (2018) Overexpression of transforming growth factor ? induced factor homeobox 1 represses NPC1L1 and lowers markers of intestinal cholesterol absorption. Atherosclerosis 275:246-255

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