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 interprogrammatic 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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA044579-22
Application #
8566488
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
22
Fiscal Year
2013
Total Cost
$26,524
Indirect Cost
$10,827
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Heuslein, Joshua L; Murrell, Kelsey P; Leiphart, Ryan J et al. (2016) Vascular growth responses to chronic arterial occlusion are unaffected by myeloid specific focal adhesion kinase (FAK) deletion. Sci Rep 6:27029
Ma, Zhenjun; Kim, Youngchul; Hu, Feifang et al. (2016) Point success rate for patient therapeutic response prediction by continuous biomarker scores. Stat Methods Med Res 25:1638-47
Mauldin, Ileana S; Wages, Nolan A; Stowman, Anne M et al. (2016) Topical treatment of melanoma metastases with imiquimod, plus administration of a cancer vaccine, promotes immune signatures in the metastases. Cancer Immunol Immunother 65:1201-12
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Mauldin, Ileana S; Wages, Nolan A; Stowman, Anne M et al. (2016) Intratumoral interferon-gamma increases chemokine production but fails to increase T cell infiltration of human melanoma metastases. Cancer Immunol Immunother 65:1189-99
Cross, A M; Wilson, A L; Guerrero, M S et al. (2016) Breast cancer antiestrogen resistance 3-p130(Cas) interactions promote adhesion disassembly and invasion in breast cancer cells. Oncogene 35:5850-5859
Kolpaczynska, Milena; DeRosa, Christopher A; Morris, William A et al. (2016) Thienyl Difluoroboron β-Diketonates in Solution and Polylactide Media. Aust J Chem 69:537-545
Sloane, Hillary S; Landers, James P; Kelly, Kimberly A (2016) Hybridization-Induced Aggregation Technology for Practical Clinical Testing: KRAS Mutation Detection in Lung and Colorectal Tumors. J Mol Diagn 18:546-53
Cheng, Bei; He, Huacheng; Huang, Tao et al. (2016) Gold Nanosphere Gated Mesoporous Silica Nanoparticle Responsive to Near-Infrared Light and Redox Potential as a Theranostic Platform for Cancer Therapy. J Biomed Nanotechnol 12:435-49

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