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.
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.
|Harder, Bryan; Tian, Wang; La Clair, James J et al. (2017) Brusatol overcomes chemoresistance through inhibition of protein translation. Mol Carcinog 56:1493-1500|
|Chen, Yufei; Anastassiadis, Konstantinos; Kranz, Andrea et al. (2017) MLL2, Not MLL1, Plays a Major Role in Sustaining MLL-Rearranged Acute Myeloid Leukemia. Cancer Cell 31:755-770.e6|
|DeRyckere, Deborah; Lee-Sherick, Alisa B; Huey, Madeline G et al. (2017) UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models. Clin Cancer Res 23:1481-1492|
|Scarborough, Hannah A; Helfrich, Barbara A; Casás-Selves, Matias et al. (2017) AZ1366: An Inhibitor of Tankyrase and the Canonical Wnt Pathway that Limits the Persistence of Non-Small Cell Lung Cancer Cells Following EGFR Inhibition. Clin Cancer Res 23:1531-1541|
|Neelakantan, Deepika; Zhou, Hengbo; Oliphant, Michael U J et al. (2017) EMT cells increase breast cancer metastasis via paracrine GLI activation in neighbouring tumour cells. Nat Commun 8:15773|
|Barón, Anna E; Kako, Severine; Feser, William J et al. (2017) Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer. J Thorac Oncol 12:1512-1523|
|Todd, Maria C; Langan, Thomas A; Sclafani, Robert A (2017) Doxycycline-Regulated p16MTS1 Expression Suppresses the Anchorage-Independence and Tumorigenicity of Breast Cancer Cell Lines that Lack Endogenous p16. J Cancer 8:190-198|
|Brown, Dustin G; Borresen, Erica C; Brown, Regina J et al. (2017) Heat-stabilised rice bran consumption by colorectal cancer survivors modulates stool metabolite profiles and metabolic networks: a randomised controlled trial. Br J Nutr 117:1244-1256|
|Haverkos, Bradley M; Abbott, Diana; Hamadani, Mehdi et al. (2017) PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 130:221-228|
|Shearn, Colin T; Saba, Laura M; Roede, James R et al. (2017) Differential carbonylation of proteins in end-stage human fatty and nonfatty NASH. Free Radic Biol Med 113:280-290|
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