;The Drug Discovery and Structural Biology Core (DDSB) is a new shared resource that supports the identification and development of small molecule and macromolecular therapeutics for the basic, translational and clinical scientists at COHCCC. The overarching goal of DDSB is to provide the necessary scientific resources to assist In chemical biology studies and development of molecularly-based therapeutics. DDSB comprises several scientific disciplines that include medicinal chemistry, biopolymer synthesis, high throughput screening, and X-ray crystallography. Rather than have separate cores for each, these disciplines are consolidated under one unit for maximum efficiency in drug development. This has resulted in unique shared resource that works in concert to achieve the basic and translational research goals of the Cancer Center. Specific areas of expertise and services provided include: synthetic organic chemistry, custom synthesis of specialized RNA and DNA, assay development, high-throughput screening, protein production, biophysical characterization and structural biology. The amalgamation of these services provides a seamless drug discovery pipeline for development of novel molecular targets. The DDSB core is focused yet flexible to allow Cancer Center members to use any one of these services individually or in combination. An additional significant component of the DDSB is to consult with Pis, develop reagents and assays, and obtain preliminary results to support the application of externally funded proposals by Cancer Center members. For example, the DDSB has developed COH29, a novel small-molecule inhibitor that is a dual PARP/rlbonucleotide reductase antagonist and has promising activity against BRCA1 deficient cancers. This work has led to new ROI funding and our first drug candidate for GMP synthesis and clinical trials developed completely in-house. Collectively, the DDSB serves as a scientific and intellectual hub for Integrating diverse disciplines such as molecular modeling, bioinformatics, and pharmacology in a transdisciplinary approach towards the development of new agents for the treatment of cancer. The DDSB Is unique in this capacity as it provides a complete program of scientific services and coordination of efforts for drug discovery in an academic setting. Thus, Pis can leverage the DDSB core for pursuing avenues of research not previously available at one site in an academic center, thereby accelerating the development of chemical biology probes and molecularly-targeted therapies for clinic trials at COHCCC.

Public Health Relevance

The overall goal of the Drug Discovery and Structural Biology core facility is to support drug development efforts within COHCCC, utilizing advanced capabilities and equipment to develop next-generation, molecularly-targeted cancer therapeutics. This goal promotes the Cancer Center's dedication to developing innovative new disease-fighting strategies In the battle against cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA033572-31
Application #
8764851
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
31
Fiscal Year
2014
Total Cost
$156,449
Indirect Cost
$63,325
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Aslamy, Arianne; Oh, Eunjin; Olson, Erika M et al. (2018) Doc2b Protects ?-Cells Against Inflammatory Damage and Enhances Function. Diabetes 67:1332-1344
Zhao, Xingli; Zhang, Zhuoran; Moreira, Dayson et al. (2018) B Cell Lymphoma Immunotherapy Using TLR9-Targeted Oligonucleotide STAT3 Inhibitors. Mol Ther 26:695-707
Weitzel, Jeffrey N; Chao, Elizabeth C; Nehoray, Bita et al. (2018) Somatic TP53 variants frequently confound germ-line testing results. Genet Med 20:809-816
Ghose, Jayeeta; Viola, Domenico; Terrazas, Cesar et al. (2018) Daratumumab induces CD38 internalization and impairs myeloma cell adhesion. Oncoimmunology 7:e1486948
Castanotto, Daniela; Zhang, Xiaowei; Alluin, Jessica et al. (2018) A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus. Proc Natl Acad Sci U S A 115:E5756-E5765
Awasthi, Sanjay; Tompkins, Joshua; Singhal, Jyotsana et al. (2018) Rlip depletion prevents spontaneous neoplasia in TP53 null mice. Proc Natl Acad Sci U S A 115:3918-3923
Röth, Daniel; Chiang, Abby J; Hu, Weidong et al. (2018) Two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation. FASEB J :fj201801848R
Li, Yi-Jia; Du, Li; Aldana-Masangkay, Grace et al. (2018) Regulation of miR-34b/c-targeted gene expression program by SUMOylation. Nucleic Acids Res 46:7108-7123
Adamus, Tomasz; Kortylewski, Marcin (2018) The revival of CpG oligonucleotide-based cancer immunotherapies. Contemp Oncol (Pozn) 22:56-60
Chaurasiya, Shyambabu; Chen, Nanhai G; Fong, Yuman (2018) Oncolytic viruses and immunity. Curr Opin Immunol 51:83-90

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