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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA044579-23
Application #
8635287
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
23
Fiscal Year
2014
Total Cost
$6,948
Indirect Cost
$3,666
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Knapp, Kiley A; Pires, Eusebio S; Adair, Sara J et al. (2018) Evaluation of SAS1B as a target for antibody-drug conjugate therapy in the treatment of pancreatic cancer. Oncotarget 9:8972-8984
Kedzierska, Katarzyna Z; Gerber, Livia; Cagnazzi, Daniele et al. (2018) SONiCS: PCR stutter noise correction in genome-scale microsatellites. Bioinformatics 34:4115-4117
Zhang, Xuewei; Kitatani, Kazuyuki; Toyoshima, Masafumi et al. (2018) Ceramide Nanoliposomes as a MLKL-Dependent, Necroptosis-Inducing, Chemotherapeutic Reagent in Ovarian Cancer. Mol Cancer Ther 17:50-59
Cruickshanks, Nichola; Zhang, Ying; Hine, Sarah et al. (2018) Discovery and Therapeutic Exploitation of Mechanisms of Resistance to MET Inhibitors in Glioblastoma. Clin Cancer Res :
Balogh, Kristen N; Templeton, Dennis J; Cross, Janet V (2018) Macrophage Migration Inhibitory Factor protects cancer cells from immunogenic cell death and impairs anti-tumor immune responses. PLoS One 13:e0197702
Gonzalez, Phillippe P; Kim, Jungeun; Galvao, Rui Pedro et al. (2018) p53 and NF 1 loss plays distinct but complementary roles in glioma initiation and progression. Glia 66:999-1015
Rodriguez, Anthony B; Peske, J David; Engelhard, Victor H (2018) Identification and Characterization of Tertiary Lymphoid Structures in Murine Melanoma. Methods Mol Biol 1845:241-257
Stowman, Anne M; Hickman, Alexandra W; Mauldin, Ileana S et al. (2018) Lymphoid aggregates in desmoplastic melanoma have features of tertiary lymphoid structures. Melanoma Res 28:237-245
Melhuish, Tiffany A; Kowalczyk, Izabela; Manukyan, Arkadi et al. (2018) Myt1 and Myt1l transcription factors limit proliferation in GBM cells by repressing YAP1 expression. Biochim Biophys Acta Gene Regul Mech 1861:983-995
Kulling, Paige M; Olson, Kristine C; Olson, Thomas L et al. (2018) Calcitriol-mediated reduction in IFN-? output in T cell large granular lymphocytic leukemia requires vitamin D receptor upregulation. J Steroid Biochem Mol Biol 177:140-148

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