Drug Discovery and Structural Biology Shared Resource ABSTRACT The Drug Discovery and Structural Biology (DDSB) Core collaborates with City of Hope investigators to validate, develop, and optimize novel therapeutics. To accomplish this, the DDSB provides a comprehensive range of services spanning computational methods; high throughput screening (HTS); advanced synthetic methods to produce small molecules, peptides, and challenging oligonucleotides; and structural and biophysical methods. These services provide City of Hope Comprehensive Cancer Center (COHCCC) members with a cohesive platform to rapidly and successfully drive their therapeutic development efforts to meaningful outcomes. All major equipment and instrumentation for the DDSB is located in the Flower building. This includes an extensive array of liquid handling robots; peptide and oligonucleotide synthesizers; multiple incubators and fast protein liquid chromatography (FPLC) systems for protein production and purification; analytical instrumentation to characterize molecular interactions (surface plasmon resonance [SPR], isothermal titration calorimetry [ITC], analytical ultracentrifugation, circular dichroism [CD] with thermal control, etc.); NMR and mass spectrometers for small molecules; and equipment for macromolecular determinations (crystallization and visualization robots and a diffractometer). The DDSB core is co-directed by Drs. David Horne and John Williams, Professors in the Department of Molecular Medicine at the Beckman Research Institute at City of Hope, and supported by highly qualified staff that maintain and operate the equipment while also providing training to COHCCC researchers who wish to operate instruments independently. Oversight is provided by an interdisciplinary faculty Advisory Committee, and user feedback through an annual survey. Since the last competitive renewal, the core contributed to 219 publications by CC members, served 121 unique investigators, 100 (83%) of whom were CC members and represent all five Programs. Of the 100 CC members, 86 had peer-reviewed funding. In addition, since the last competitive renewal, the DDSB has synthesized more than 300 small molecules, 500 peptides, and 950 oligonucleotides (aptamers, GpC-conjugates, etc.). During that same period, over 450 crystallization and optimization trials were conducted, over 250 crystals were screened for diffraction, over 40 novel crystal structures/complexes were determined, and over 300 SPR experiments, 35 in silico screening/molecular dynamics projects, and 23 HTS projects were conducted. The DDSB has also developed synthetic methods and processes leading to full-scale production of complex small molecules under GMP conditions. Efforts stemming from the DDSB have led to 32 technology/patent portfolios involving 76 patents (pending and allowed), four licenses, and a substantial sponsored research agreement (>$1M).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA033572-38
Application #
10059201
Study Section
Subcommittee I - Transistion to Independence (NCI)
Program Officer
Roberson, Sonya
Project Start
1997-08-01
Project End
2022-11-30
Budget Start
2020-12-01
Budget End
2021-11-30
Support Year
38
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Beckman Research Institute/City of Hope
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Chaurasiya, Shyambabu; Chen, Nanhai G; Fong, Yuman (2018) Oncolytic viruses and immunity. Curr Opin Immunol 51:83-90
Liu, Stephen V; Groshen, Susan G; Kelly, Karen et al. (2018) A phase I trial of topotecan plus tivantinib in patients with advanced solid tumors. Cancer Chemother Pharmacol 82:723-732
Maestrini, Davide; Abler, Daniel; Adhikarla, Vikram et al. (2018) Aging in a Relativistic Biological Space-Time. Front Cell Dev Biol 6:55
Adamus, Tomasz; Kortylewski, Marcin (2018) The revival of CpG oligonucleotide-based cancer immunotherapies. Contemp Oncol (Pozn) 22:56-60
Dufva, Olli; Kankainen, Matti; Kelkka, Tiina et al. (2018) Aggressive natural killer-cell leukemia mutational landscape and drug profiling highlight JAK-STAT signaling as therapeutic target. Nat Commun 9:1567
Chen, Steven F; Liu, Zheng; Chaurasiya, Shyambabu et al. (2018) Identification of core aberrantly expressed microRNAs in serous ovarian carcinoma. Oncotarget 9:20451-20466
Petrossian, Karineh; Nguyen, Duc; Lo, Chiao et al. (2018) Use of dual mTOR inhibitor MLN0128 against everolimus-resistant breast cancer. Breast Cancer Res Treat 170:499-506
Murray, Jennifer; Whitson, Robert H; Itakura, Keiichi (2018) Reduced prostaglandin I2 signaling in Arid5b-/- primary skeletal muscle cells attenuates myogenesis. FASEB J 32:1868-1879
Sun, Virginia; Crane, Tracy E; Slack, Samantha D et al. (2018) Rationale, development, and design of the Altering Intake, Managing Symptoms (AIMS) dietary intervention for bowel dysfunction in rectal cancer survivors. Contemp Clin Trials 68:61-66
Li, Daneng; McCall, Linda M; Hahn, Olwen M et al. (2018) Identification of risk factors for toxicity in patients with hormone receptor-positive advanced breast cancer treated with bevacizumab plus letrozole: a CALGB 40503 (alliance) correlative study. Breast Cancer Res Treat 171:325-334

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