; 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 #
5P30CA033572-34
Application #
9179606
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
1997-08-01
Project End
2018-03-31
Budget Start
2016-12-01
Budget End
2017-11-30
Support Year
34
Fiscal Year
2017
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
Tirughana, Revathiswari; Metz, Marianne Z; Li, Zhongqi et al. (2018) GMP Production and Scale-Up of Adherent Neural Stem Cells with a Quantum Cell Expansion System. Mol Ther Methods Clin Dev 10:48-56
Raz, Dan J; Wu, Geena X; Consunji, Martin et al. (2018) The Effect of Primary Care Physician Knowledge of Lung Cancer Screening Guidelines on Perceptions and Utilization of Low-Dose Computed Tomography. Clin Lung Cancer 19:51-57
Solomon, Ilana; Rybak, Christina; Van Tongeren, Lily et al. (2018) Experience Gained from the Development and Execution of a Multidisciplinary Multi-syndrome Hereditary Colon Cancer Family Conference. J Cancer Educ :
Wang, Dongrui; Aguilar, Brenda; Starr, Renate et al. (2018) Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. JCI Insight 3:
Cheng, Chun-Ting; Qi, Yue; Wang, Yi-Chang et al. (2018) Arginine starvation kills tumor cells through aspartate exhaustion and mitochondrial dysfunction. Commun Biol 1:178
Cho, H; Ayers, K; DePills, L et al. (2018) Modelling acute myeloid leukaemia in a continuum of differentiation states. Lett Biomath 5:S69-S98
Querfeld, Christiane; Leung, Samantha; Myskowski, Patricia L et al. (2018) Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile. Cancer Immunol Res 6:900-909
Liu, Xuxiang; Cao, Minghui; Palomares, Melanie et al. (2018) Metastatic breast cancer cells overexpress and secrete miR-218 to regulate type I collagen deposition by osteoblasts. Breast Cancer Res 20:127
Das, Sadhan; Reddy, Marpadga A; Senapati, Parijat et al. (2018) Diabetes Mellitus-Induced Long Noncoding RNA Dnm3os Regulates Macrophage Functions and Inflammation via Nuclear Mechanisms. Arterioscler Thromb Vasc Biol 38:1806-1820
Al Malki, Monzr M; Nathwani, Nitya; Yang, Dongyun et al. (2018) Melphalan-Based Reduced-Intensity Conditioning is Associated with Favorable Disease Control and Acceptable Toxicities in Patients Older Than 70 with Hematologic Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant 24:1828-1835

Showing the most recent 10 out of 1396 publications