The Chemical Library Screening Shared Resource (CLS) offers Cancer Center scientists the ability to develop and conduct large-scale chemical library screens for the generation of selective probes of biochemical processes of tumor biology and for the discovery of compounds that can be developed further as drug leads for therapeutic applications. High-throughput screening is not widely available at academic institutions;thus, this resource provides our Cancer Center with rare access to technology, expertise and infrastructure resources that will enable them to develop novel means for characterizing cellular targets involved in tumor pathogenesis and tumor onset that will advance the development of new lead molecules for anti-tumor therapies. The CLS consists of 4 specialized but highly integrated facilities: 1) the High Throughput Assay Development Facility supports the development, miniaturization, optimization, and validation of biochemical and cell-based high throughput assays, as well as supports follow-up analysis of screens, including IC50 determination, structure-activity-relationship (SAR) and mechanism-of-action studies;2) the Compound Management and HT Screening Facility, that curates the Institute's compound collections and performs the large-scale automated screening;3) the High Content Screening (HCS) Facility that supports imagebased high content assays utilizing high throughput microscopy, as well as automated microscopy for nonscreening applications - This facility also supports the image-based screening efforts of the Functional Genomics Shared Resource;and 4) the Medicinal Chemistry Facility provides both technical and scientific assistance in medicinal chemistry, synthesis, structure-activity relationship development, and generates optimized compounds for preclinical studies. CLS supported over half (34) of the Cancer Center laboratories in the last year. Chemical genomics has become a major focus of the Burnham Cancer Center, and has many opportunities for providing insight into potential therapeutic targets and strategies. CCSG funding of CLS leverages a substantial Institutional and NIH MLPCN investment in the Center for Chemical Genomics infrastructure, and is critical to bringing this cutting edge technology to Cancer Center researchers by funding facility personnel that conduct their projects. Overall, $189,798 in CCSG support is requested in the first year, representing 10.5% of the total projected annual CLS Shared Resource operating budget.

Public Health Relevance

Chemical biology can both elucidate the function of proteins involved in tumor development and progression, and identify novel targets and lead compounds with therapeutic potential in treating human cancers. The unique combination of basic cancer biology studies supported by extensive resources and expertise to perform high throughput screening and medicinal chemistry will lead to important new findings.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA030199-32
Application #
8473804
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
32
Fiscal Year
2013
Total Cost
$219,437
Indirect Cost
$100,416
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Wei, Yang; Toth, Julia I; Blanco, Gabrielle A et al. (2018) Adapted ATPase domain communication overcomes the cytotoxicity of p97 inhibitors. J Biol Chem 293:20169-20180
Tinoco, Roberto; Carrette, Florent; Henriquez, Monique L et al. (2018) Fucosyltransferase Induction during Influenza Virus Infection Is Required for the Generation of Functional Memory CD4+ T Cells. J Immunol 200:2690-2702
Wonder, Emily; Simón-Gracia, Lorena; Scodeller, Pablo et al. (2018) Competition of charge-mediated and specific binding by peptide-tagged cationic liposome-DNA nanoparticles in vitro and in vivo. Biomaterials 166:52-63
Limpert, Allison S; Lambert, Lester J; Bakas, Nicole A et al. (2018) Autophagy in Cancer: Regulation by Small Molecules. Trends Pharmacol Sci 39:1021-1032
Fujita, Yu; Khateb, Ali; Li, Yan et al. (2018) Regulation of S100A8 Stability by RNF5 in Intestinal Epithelial Cells Determines Intestinal Inflammation and Severity of Colitis. Cell Rep 24:3296-3311.e6
Scully, Kathleen M; Lahmy, Reyhaneh; Signaevskaia, Lia et al. (2018) E47 Governs the MYC-CDKN1B/p27KIP1-RB Network to Growth Arrest PDA Cells Independent of CDKN2A/p16INK4A and Wild-Type p53. Cell Mol Gastroenterol Hepatol 6:181-198
Borlido, Joana; Sakuma, Stephen; Raices, Marcela et al. (2018) Nuclear pore complex-mediated modulation of TCR signaling is required for naïve CD4+ T cell homeostasis. Nat Immunol 19:594-605
Follis, Ariele Viacava; Llambi, Fabien; Kalkavan, Halime et al. (2018) Regulation of apoptosis by an intrinsically disordered region of Bcl-xL. Nat Chem Biol 14:458-465
Pathria, Gaurav; Scott, David A; Feng, Yongmei et al. (2018) Targeting the Warburg effect via LDHA inhibition engages ATF4 signaling for cancer cell survival. EMBO J 37:
Sun, Younguk; Chen, Bo-Rui; Deshpande, Aniruddha (2018) Epigenetic Regulators in the Development, Maintenance, and Therapeutic Targeting of Acute Myeloid Leukemia. Front Oncol 8:41

Showing the most recent 10 out of 599 publications