1. What does the equipment do, and how does that make it valuable for research?
This piece of equipment is specialized to identify molecular species. We have dedicated this instrument to measuring metabolites, the products of metabolic processes. The LC-MS/MS instrument can accurately quantify the abundance of a broad number of metabolites (100’s – 1,000’s) in cells, tissues, or circulation. In addition, we use this instrument to measure isotopes that we introduce to an animal or dish to “label” the metabolites. This label makes the metabolite of interest slightly heavier upon analysis and allows us to measure rates of movement of that metabolite through calculations of dilution. To use an analogy, taking a picture of a highway could tell someone how many cars are on the road and perhaps the make and color of those cars. This example is the standard metabolomic analysis. However, if a video camera was used, one would be able to determine how fast each kind of car is moving and the direction they are going. The capturing of the rates and direction of movement is the additional advantage of using an isotope. The determination of what metabolites are present and their rates of movement are both important when studying metabolism. These approaches are complicated, and there are relatively few labs in the United States that can do it well.
2. Over the last year, how many people have used the equipment and from what organizations?
In the first year, we have had 2 primary users. These users are from the Aging and Metabolism Research Program and Cardiovascular Biology Research Program at OMRF. We purposely minimized users the first year so that we could develop these challenging methods and templates to more efficiently apply methods for other investigators.
3. What are some important findings that were made possible with the equipment?
One of our users is interested in understanding flux through energy producing pathways (such as glycolysis and TCA cycle) in ovarian cancer cells. There is evidence that when an isoform of the enzyme succinate dehydrogenase (SDH) is overexpressed, ovarian cancer cells become more sensitive to chemotherapies, thus improving patient survival. Since SDH is a critical enzyme that links glycolysis to aerobic energy production, we investigated how overexpression of SDH changes energy metabolism in ovarian cancer cells. By doing these studies, we found that our original pathway of interest was probably not the one on which we should focus. Instead, we found that another pathway was providing the substrates to change the aerobic metabolism. These findings have shifted the focus to drug candidates that more directly impact the alternative energy-producing pathways.
4. What other information would you like to share?
This instrument is operated with support from the Center for Cellular Metabolism Research in Oklahoma (CMRO) Phase I COBRE as part of the Metabolic Phenotyping Core at OMRF (click here). Method development and support is prioritized for the CMRO project leaders and affiliates. Support for other Oklahoma investigators will be provided based on instrument availability, method development requirements, and financial support. While this instrument can do a variety of different types of measurements, our initial focus is on the analysis of the abundance of cellular metabolites and their movements within a cellular system.
