Core D is critical for the central tenet ofthe UCLA-CMCR, which is that classes of mitigators of radiation damage can be identified by their chemical structures and/or the biological pathways that they utilize. Core D has provided and will continue to provide the technological driving force behind the work ofthe projects in high-throughput screening (HTS) of small molecule libraries with the aim of discovering novel mitigators of radiation damage. Core D centralizes HTS in a state-of-the-art facility that has already proven its value to the UCLA-CMCR, with several families of lead compounds identified. Additionally, in order to deal with the data that has been generated and to provide it to the CMCR in a form in which it can be mined for structureactivity relationships and other relevant chemical and biological information Core D, through pilot research funding, has established a relationship with Collaborative Drug Discovery (CDD) to use its an industrialstrength database for these purposes. Access to this data is available to other CMCRs. Now that families of lead compounds have been identified, with more to come. Core D has been further expanded to include pharmaceutical chemists under Dr. Jung, who will play a central role in design and synthesis of analogues of active compounds to identify chemical structures responsible for activity, to improve their drug-like qualities, and their efficacy. This relationship also was initiated through pilot research funding. Finally, Core D provides proteomics primarily in the form of mass spectrometry to seek molecular signatures ofthe biological pathways utilized by effective mitigators so as to probe mechanism of action of these compounds.

Public Health Relevance

Core D brings technology that allows us to measure the effects of many thousands of compounds on the response of cells to radiation so as to discover novel agents;an industrial-strength database to house the data and explore it to derive information;the ability to chemically improve active compounds and investigate structure-activity relationships;and to define the pathways by which they bring about their effects.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Los Angeles
United States
Zip Code
Micewicz, Ewa D; Luong, Hai T; Jung, Chun-Ling et al. (2014) Novel dimeric Smac analogs as prospective anticancer agents. Bioorg Med Chem Lett 24:1452-7
Damoiseaux, Robert (2014) UCLA's Molecular Screening Shared Resource: enhancing small molecule discovery with functional genomics and new technology. Comb Chem High Throughput Screen 17:356-68
Erde, Jonathan; Loo, Rachel R Ogorzalek; Loo, Joseph A (2014) Enhanced FASP (eFASP) to increase proteome coverage and sample recovery for quantitative proteomic experiments. J Proteome Res 13:1885-95
Bunimovich, Yuri L; Nair-Gill, Evan; Riedinger, Mireille et al. (2014) Deoxycytidine kinase augments ATM-Mediated DNA repair and contributes to radiation resistance. PLoS One 9:e104125
Martin, N T; Nakamura, K; Paila, U et al. (2014) Homozygous mutation of MTPAP causes cellular radiosensitivity and persistent DNA double-strand breaks. Cell Death Dis 5:e1130
Hacke, K; Treger, J A; Bogan, B T et al. (2013) Genetic modification of mouse bone marrow by lentiviral vector-mediated delivery of hypoxanthine-Guanine phosphoribosyltransferase short hairpin RNA confers chemoprotection against 6-thioguanine cytotoxicity. Transplant Proc 45:2040-4
Martin, Nathan T; Nakamura, Kotoka; Davies, Robert et al. (2013) ATM-dependent MiR-335 targets CtIP and modulates the DNA damage response. PLoS Genet 9:e1003505
Xie, Michael W; Gorodetsky, Raphael; Micewicz, Ewa D et al. (2013) Marrow-derived stromal cell delivery on fibrin microbeads can correct radiation-induced wound-healing deficits. J Invest Dermatol 133:553-61
Ambrose, Mark; Gatti, Richard A (2013) Pathogenesis of ataxia-telangiectasia: the next generation of ATM functions. Blood 121:4036-45
Li, Xinmin; Zhou, Jian; Nahas, Shareef A et al. (2012) Common copy number variations in fifty radiosensitive cell lines. Genomics 99:96-100

Showing the most recent 10 out of 63 publications