;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
Gast, Charles E; Silk, Alain D; Zarour, Luai et al. (2018) Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival. Sci Adv 4:eaat7828
Salgia, Ravi; Kulkarni, Prakash (2018) The Genetic/Non-genetic Duality of Drug 'Resistance' in Cancer. Trends Cancer 4:110-118
Yoon, Sorah; Wu, Xiwei; Armstrong, Brian et al. (2018) An RNA Aptamer Targeting the Receptor Tyrosine Kinase PDGFR? Induces Anti-tumor Effects through STAT3 and p53 in Glioblastoma. Mol Ther Nucleic Acids 14:131-141
Yim, John H; Choi, Audrey H; Li, Arthur X et al. (2018) Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule Diagnostics. Clin Cancer Res :
Wang, Tianyi; Fahrmann, Johannes Francois; Lee, Heehyoung et al. (2018) JAK/STAT3-Regulated Fatty Acid ?-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance. Cell Metab 27:136-150.e5
Magilnick, Nathaniel; Boldin, Mark P (2018) Molecular Moirai: Long Noncoding RNA Mediators of HSC Fate. Curr Stem Cell Rep 4:158-165
Yun, Xinwei; Zhang, Keqiang; Wang, Jinhui et al. (2018) Targeting USP22 Suppresses Tumorigenicity and Enhances Cisplatin Sensitivity Through ALDH1A3 Downregulation in Cancer-Initiating Cells from Lung Adenocarcinoma. Mol Cancer Res 16:1161-1171
Herrera, Alex F; Rodig, Scott J; Song, Joo Y et al. (2018) Outcomes after Allogeneic Stem Cell Transplantation in Patients with Double-Hit and Double-Expressor Lymphoma. Biol Blood Marrow Transplant 24:514-520
Slavin, Thomas P; Banks, Kimberly C; Chudova, Darya et al. (2018) Identification of Incidental Germline Mutations in Patients With Advanced Solid Tumors Who Underwent Cell-Free Circulating Tumor DNA Sequencing. J Clin Oncol :JCO1800328
Shahin, Sophia A; Wang, Ruining; Simargi, Shirleen I et al. (2018) Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer. Nanomedicine 14:1381-1394

Showing the most recent 10 out of 1396 publications