Objective: The Structural Biology Shared Resource (SBSR) provides UCCC researchers access to instrumentation and expertise in X-ray Crystallography and Nuclear Magnetic Resonance Spectroscopy, promoting the application of macromolecular structural studies to cancer research. Projects studied in the Core include hormone receptor and transcription regulator structures, telomere structures, tumor suppressor structures, phospholipid targeting domain structures, tumor cell surface marker structures, and chromatin assembly and disassembly structures, among others, and have resulted in >50 research publications, including many publications in high profile journals such as Cell, Nature, Science, Molecular Cell, and Nature Structural and Molecular Biology. Services &Technologies: The facilities available within the resource have expanded significantly over the last 5 years. The X-ray Core facility has 2 Raxis IV++ area detectors with a Rigaku/MSC generator and has added Rigaku/MSC robotic systems for production of crystallization screens, drop setting and plate imaging. The NMR Core facility has added a 900 MHz Varian NMR spectrometer to the existing 500 and 600 MHz spectrometers at the Anschutz Medical Campus and has added a Varian 800 MHz spectrometer at the University of Colorado Boulder campus. Consultation &Training: SBSR personnel provide sample preparation, data collection and instrument training and help investigators process data, determine structures, and prepare data for publication and presentation. Utilization: In the last year, the SBSR supported the operation of more than 30 research programs including 18 UCCC members (with ~$3.8 million of annual direct costs in grant support) from 4 different UCCC Programs and 3 UCCC consortium institutions (UCD AMC, National Jewish Health, UC Boulder). UCCC members accounted for 88% of the total usage of the facilities. Management &Finances: SBSR is UCCC managed. Approximately one-quarter of the grants serviced by the SBSR are NCI-funded;however, many of the grants funded by other NIH agencies are specifically cancer-related. Other funding has come from the American Cancer Society, Cancer League of Colorado and the National Science Foundation. In the previous year, 43% of the operating budget came from chargebacks to UCCC members who represent >90% of users. The SBSR requests $180,693 CCSG support for 40% of its operating budget. Developing facilities for structural biology research will continue, and two primary future objectives are 1) develop new projects from non-structure labs, and 2) promote closer integration with clinical research as part of target validation.

Public Health Relevance

Researchers in the Structural Biology Shared Resource determine the 3-dimensional structures of the proteins, other cellular macromolecules and their complexes that affect the development and progression of cancer, and of small molecules, potential drugs and their interactions with their therapeutic targets. Structures of molecules implicated in cancer provide clues to potential therapies.

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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University of Colorado Denver
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Helfrich, Barbara A; Gao, Dexiang; Bunn Jr, Paul A (2018) Eribulin inhibits the growth of small cell lung cancer cell lines alone and with radiotherapy. Lung Cancer 118:148-154
Oweida, Ayman; Phan, Andy; Vancourt, Benjamin et al. (2018) Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer. Thyroid 28:739-747
Gadalla, Shahinaz M; Wang, Tao; Loftus, David et al. (2018) No association between donor telomere length and outcomes after allogeneic unrelated hematopoietic cell transplant in patients with acute leukemia. Bone Marrow Transplant 53:383-391
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Bagati, Archis; Bianchi-Smiraglia, Anna; Moparthy, Sudha et al. (2018) FOXQ1 controls the induced differentiation of melanocytic cells. Cell Death Differ 25:1040-1049
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Conroy, Shannon M; Shariff-Marco, Salma; Yang, Juan et al. (2018) Characterizing the neighborhood obesogenic environment in the Multiethnic Cohort: a multi-level infrastructure for cancer health disparities research. Cancer Causes Control 29:167-183
Kleczko, Emily K; Heasley, Lynn E (2018) Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor tyrosine kinase inhibitors and inherent therapeutic vulnerabilities. Mol Cancer 17:60
Tuttle, Kathryn D; Krovi, S Harsha; Zhang, Jingjing et al. (2018) TCR signal strength controls thymic differentiation of iNKT cell subsets. Nat Commun 9:2650

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