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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI067769-09
Application #
8513246
Study Section
Special Emphasis Panel (ZAI1-KS-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
9
Fiscal Year
2013
Total Cost
$432,074
Indirect Cost
$139,836
Name
University of California Los Angeles
Department
Type
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Micewicz, Ewa D; Sharma, Shantanu; Waring, Alan J et al. (2016) Bridged Analogues for p53-Dependent Cancer Therapy Obtained by S-Alkylation. Int J Pept Res Ther 22:67-81
Wang, Wenyuan; Org, Tonis; Montel-Hagen, Amélie et al. (2016) MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis. Nat Commun 7:12376
Ratikan, Josephine A; Micewicz, Ewa D; Xie, Michael W et al. (2015) Radiation takes its Toll. Cancer Lett 368:238-45
Micewicz, Ewa D; Ratikan, Josephine A; Waring, Alan J et al. (2015) Lipid-conjugated Smac analogues. Bioorg Med Chem Lett 25:4419-27
Micewicz, Ewa D; Bahattab, Omar S O; Willars, Gary B et al. (2015) Small lipidated anti-obesity compounds derived from neuromedin U. Eur J Med Chem 101:616-26
Pai, Melody Y; Lomenick, Brett; Hwang, Heejun et al. (2015) Drug affinity responsive target stability (DARTS) for small-molecule target identification. Methods Mol Biol 1263:287-98
Schaue, Dörthe; Micewicz, Ewa D; Ratikan, Josephine A et al. (2015) Radiation and inflammation. Semin Radiat Oncol 25:4-10
Schaue, Dörthe; McBride, William H (2015) Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol 12:527-40
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

Showing the most recent 10 out of 78 publications