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 therapeufic agents. The merging of the structural and chemical biology faculfies 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 currenfiy 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 Insfitute (NCI) and more than $8.8 million from other National Insfitutes of Health (NIH) entities. The Program Members rely heavily on Cancer Center-supported infrastructure, particulariy 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 activifies and interactions of CSB Members have led to 287 publicafions, of which 29% were interprogrammatic publicafions 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 #
2P30CA044579-21
Application #
8231121
Study Section
Subcommittee G - Education (NCI)
Project Start
2012-02-01
Project End
2017-01-31
Budget Start
2012-06-05
Budget End
2013-01-31
Support Year
21
Fiscal Year
2012
Total Cost
$25,279
Indirect Cost
$9,246
Name
University of Virginia
Department
Type
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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
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
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
Carlton, Anne L; Illendula, Anuradha; Gao, Yan et al. (2018) Small molecule inhibition of the CBF?/RUNX interaction decreases ovarian cancer growth and migration through alterations in genes related to epithelial-to-mesenchymal transition. Gynecol Oncol 149:350-360
Borten, Michael A; Bajikar, Sameer S; Sasaki, Nobuo et al. (2018) Automated brightfield morphometry of 3D organoid populations by OrganoSeg. Sci Rep 8:5319
Olson, Kristine C; Kulling Larkin, Paige M; Signorelli, Rossana et al. (2018) Vitamin D pathway activation selectively deactivates signal transducer and activator of transcription (STAT) proteins and inflammatory cytokine production in natural killer leukemic large granular lymphocytes. Cytokine 111:551-562
Pfister, Katherine; Pipka, Justyna L; Chiang, Colby et al. (2018) Identification of Drivers of Aneuploidy in Breast Tumors. Cell Rep 23:2758-2769
Carhart, Miev Y; Schminkey, Donna L; Mitchell, Emma M et al. (2018) Barriers and Facilitators to Improving Virginia's HPV Vaccination Rate: A Stakeholder Analysis With Implications for Pediatric Nurses. J Pediatr Nurs 42:1-8
Hao, Yi; Bjerke, Glen A; Pietrzak, Karolina et al. (2018) TGF? signaling limits lineage plasticity in prostate cancer. PLoS Genet 14:e1007409
Obeid, Joseph M; Kunk, Paul R; Zaydfudim, Victor M et al. (2018) Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time? Cancer Immunol Immunother 67:161-174

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