CORE C: Bioenergetics Profiling Core Director: Craig Cano Beeson, Ph.D. Professor, Department of Drug Discovery and Biomedical Sciences Project Summary The primary goal of the Bioenergetics Profiling core facility is to support COBRE investigators in the characterization of metabolite fluxes related to cellular redox and primary energy metabolism ? the prevalent sources of both the primary and secondary cellular redox species. The facility provides access to traditional, `gold standard' techniques such as isotopomer, radiometric, and spectroscopic analyses. The core is also a development site for the Seahorse Biosciences extracellular flux (XF) fluorometric technology used to measure metabolic fluxes (i.e., oxygen consumption, CO2 and lactate extrusion) in real time using multiwell plates. The basic Seahorse XF applications enable high throughput metabolic measurements with small sample sizes that have transformed the utility of quantitative analyses of metabolic fluxes. Innovative adaptations of the XF technologies developed in the core facility are providing access to real time flux measurements of redox species in cells and tissues and, more importantly, the interrogation of bioenergetics pathways via use of pharmacological or genetic interventions. We have coordinated these recent strategic technological acquisitions into a core that provides analytical support for the efforts of the COBRE investigators and their collaborators while also extending the technology to suit new efforts and further enable measurements with improved translational potential. In the COBRE Phase I stage the core was known as the ?Metabolomics Core? that offered nascent Seahorse XF technology in addition to traditional single time-point quantification of metabolite concentrations via LC-MS or NMR techniques. As described below, these traditional metabolomics techniques were not as useful to the lead COBRE investigators as were the XF technologies, particularly as the latter technology advanced and traditional metabolomics has matured. Because traditional metabolomics analyses are now commercially available leading to cost reductions (much as academic DNA oligomer or peptide cores became obsolete), the metabolomics core has been renamed as the ?Bioenergetics Profiling Core? to reflect the XF services we have developed that best support our investigators, and for which there are no alternative external resources. Indeed, because XF technologies utilize living samples, it is unlikely they will be easily `out-sourced'.

Public Health Relevance

Normal biology requires energy that is obtained from the controlled breakdown of nutrients to produce highly reactive molecules that are contained within organelles to protect the other cellular constituents ? one such organelle is the mitochondrion or ?power house? of the cell. The bioenergetics profiling core provides the best tools available to quantify the nutrient breakdown reactions, failures in protective roles that enable reactive species to be released, and the damage caused that can lead to disease or pathological states.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
2P20GM103542-06
Application #
9149872
Study Section
Special Emphasis Panel (ZGM1-RCB-6 (C2))
Project Start
Project End
Budget Start
2016-08-01
Budget End
2017-07-31
Support Year
6
Fiscal Year
2016
Total Cost
$186,875
Indirect Cost
$61,875
Name
Medical University of South Carolina
Department
Type
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29403
Kim, Mi Jin; Vargas, Marcelo R; Harlan, Benjamin A et al. (2018) Nitration and Glycation Turn Mature NGF into a Toxic Factor for Motor Neurons: A Role for p75NTR and RAGE Signaling in ALS. Antioxid Redox Signal 28:1587-1602
Fang, Diana; Maldonado, Eduardo N (2018) VDAC Regulation: A Mitochondrial Target to Stop Cell Proliferation. Adv Cancer Res 138:41-69
Klauber-DeMore, Nancy; Schulte, Bradley A; Wang, Gavin Y (2018) Targeting MYC for triple-negative breast cancer treatment. Oncoscience 5:120-121
Chatterjee, Shilpak; Daenthanasanmak, Anusara; Chakraborty, Paramita et al. (2018) CD38-NAD+Axis Regulates Immunotherapeutic Anti-Tumor T Cell Response. Cell Metab 27:85-100.e8
Gibbs, Whitney S; Garrett, Sara M; Beeson, Craig C et al. (2018) Identification of dual mechanisms mediating 5-hydroxytryptamine receptor 1F-induced mitochondrial biogenesis. Am J Physiol Renal Physiol 314:F260-F268
Nunes, Shirleide Santos; Fernandes, Renata Salgado; Cavalcante, Carolina Henriques et al. (2018) Influence of PEG coating on the biodistribution and tumor accumulation of pH-sensitive liposomes. Drug Deliv Transl Res :
Monteiro, Liziane O F; Fernandes, Renata S; Oda, Caroline M R et al. (2018) Paclitaxel-loaded folate-coated long circulating and pH-sensitive liposomes as a potential drug delivery system: A biodistribution study. Biomed Pharmacother 97:489-495
Womersley, Jacqueline S; Townsend, Danyelle M; Kalivas, Peter W et al. (2018) Targeting redox regulation to treat substance use disorder using N-acetylcysteine. Eur J Neurosci :
Herr, Daniel J; Baarine, Mauhamad; Aune, Sverre E et al. (2018) HDAC1 localizes to the mitochondria of cardiac myocytes and contributes to early cardiac reperfusion injury. J Mol Cell Cardiol 114:309-319
Angel, Peggi M; Comte-Walters, Susana; Ball, Lauren E et al. (2018) Mapping Extracellular Matrix Proteins in Formalin-Fixed, Paraffin-Embedded Tissues by MALDI Imaging Mass Spectrometry. J Proteome Res 17:635-646

Showing the most recent 10 out of 109 publications