Outreach and Education

Overview

Despite rapid advances in metabolomics technologies and the need for understanding the human metabolome, metabolomics applications in biomedical research remain limited. This is partly due to the combination of lack of awareness in the value of large-scale metabolic understanding, inadequate access to high end instrumentation, and a lack of experience in experimental design, sample handling/processing, and complex data analysis and biochemical interpretation. The purpose of this Core is to provide the proper outreach, training, education, and support to overcome most barriers to integrating metabolomics approaches into mainstream basic and translational research.

The facility offer an annual hands on Workshop that covers practical experience in sample preparation, data acquisitions and reduction, accompanied by overawes of analytical and theoretical principles by the Center Staff and invited experts. The Workshop is accompanied by a one-day Symposium in which cutting edge research is presented by leading practitioners, to demonstrate how metabolic studies can be integrated into basic and translational programs. The Center runs a Pilot Program as a means to acquire preliminary data to foster the use of metabolic studies as part of a research program. The Center develops methods and validates them as SOPs that are deposited at DRCC. The Center welcomes visits by interested researchers at all levels.

What is Metabolomics?

Living cells are maintained under non-equilibrium conditions, which requires a constant input of energy. The cells must also maintain their infrastructure, and perform tissue-specific tasks, all of which need energy and raw materials. Metabolism is the set of processes that convert exogenous compounds to metabolic energy, which drives biochemical reactions within the cell, maintains homeostasis, provides the means to do work (e.g. contraction, movement, action potentials, secretion and so forth), for cellular repair, and to divide. Metabolism responds to exogenous signals as represented by diet and pollutants for example, and local environments (microenvironment) as represented by the conditions prevailing outside cells in tissues. As such, metabolism is a sensitive indicator of pathology. 

Therefore, the ability to measure global metabolism in quantitative detail is of fundamental importance in all aspects of biology. Metabolomics provides the technical means to carry out global analyses of metabolism, by identifying and quantifying a large fraction of all of the metabolites present in a cell, and how they change in response to perturbations within relevant metabolic networks. Metabolomics therefore requires high-end analytical instrumentation, of which mass spectrometry and NMR together are the most appropriate technologies. Informatics is the third critical component of metabolomics to interpret the observations in a biological context. Careful sample preparation and processing is the often overlooked first critical component in metabolomics, which is necessary to prevent excessive perturbation and degradation of the observed metabolites. And appropriate experimental design and adherence to this design is the zeroth critical component of metabolomics.

Other Definitions and Descriptions

What is Stable Isotope-Resolved Metabolomics (SIRM)?

Global metabolomics, the quantification of a large number of metabolites in tissue or biofluids can identify disease states or response to therapeutics by reference to the normal condition. However, determining specific mechanisms, such as detecting which pathways are impacted in particular cell types within a tissue by measuring metabolic fluxes, requires additional information as many metabolites are present in different amounts in different cell types or within compartments of cells, as well as participating in several pathways simultaneously. To identify the precursor-product relationships, it is necessary to distinguish different sources of carbon, nitrogen etc. which necessitates some means of “labeling” individual atoms so that their fate can be traced through metabolic pathways. Traditionally this was achieved using radioisotopes. However, stable isotopes have several advantages, including being wholly biocompatible, and also individual atoms within a metabolite are easily distinguishable by NMR and mass spectrometry.
The general approach we have developed, which we call Stable Isotope Resolved Metabolomics or SIRM, combines the power of global (untargeted) metabolic profiling with atom-resolved tracking of metabolites during metabolic transformations within cells, tissue or whole organisms. The cell culture, tissue, or organism is provided with a source metabolite that is enriched at any or all of the atoms with a stable isotope (like 13C or 15N with natural abundances 1.1 % and 0.37%, respectively), and the products are analyzed by NMR and MS at different times after treatment. The specific isotopomer and isotopologue distributions in the various product metabolites are determined, along with the total amounts of the metabolites, which together provide detailed information about the relative importance of intersecting and parallel pathways. For example, lactate can be produced directly from glucose by lactic fermentation, as well as by glutaminolysis; the relative contributions from these independent pathways is readily determined from the isotope distributions in the lactate using either 13C-enriched glucose or glutamine as labeled sources. At the same time such labeling schemes provide simultaneous information about the flow of carbon through the pentose phosphate pathway, glycolysis, hexosamine pathway, the Krebs cycle and lipid biosynthesis among others.

Webinars, and Seminars

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Prior Events

  • 2017 (Dec 14) Metabolomics Society Webinar "Introduction to Stable Isotope Resolved Metabolomics (SIRM) and Applications to Cancer Metabolism" given by A. Lane
  • 2017 (Nov 20) 2nd International Electronic Conference of Metabolomics (IECM-2) Webinar Mapping Metabolic Networks in 3D spheroids using Stable Isotope-Resolved Metabolomics given by T. Fan https://sciforum.net/conference/iecm-2/paper/5035
  • 2017 (July 20) UAB Workshop (webinar) "Exploring lung cancer metabolome – in vivo and ex vivo – for individualized medicine" given by T. Fan
  • 2014 (Nov 14) U24 Webinar "Large-Scale Metabolite determination Using Chemoselective Approaches" given by T. Fan

Outreach

Visiting Researchers

Developing research scientists of all levels are welcome to work side-by-side with the Center's core faculty and staff learning Metabolomics techniques and applying them to their particular research interests. Students and junior faculty from laboratories across campus, around the state, throughout the nation and from around the world contribute to the interdisciplinary cross-pollination of ideas that is a very important objective for the Center. Please contact Drs. Fan, Lane and Higashi for opportunities to visit.

Recent contributions have been made by the following:
  • Dan Crooks-NCI Bethesda. Metabolomics of SDH mutant kidney cancers
  • Nicola Consolini-U. Bologna. SIRM studies of COPD
  • Marilia Dias- Sao Paulo. shRNA of enzymes for SIRM studies in cancer cells.
  • Katarina Fritz-Graz, Austria. SIRM studies of ATGL
  • Sandra Gomes - Sao Paulo. Sample preparation for SIRM studies of glutaminase C in cancer cells.
  • Scott Jones – Medicine at University of Louisville. Natural products involved in pre-Parkinson’s disease symptoms.
  • Anne Le - Johns Hopkins University. SIRM analysis of MYC expression in cancer cells.
  • Santiago Moralli – University of Barcelona. High-throughput metabolite analysis, specifically the study of the lipidome and its changes during cell cycle progression and tumor transformation.
  • Jason Podrabsky - Oregon State. GC-MS analysis of killifish embryos.
  • Miriam Porquet – University of Barcelona. Study of metabolic and lipid profiles of mouse embryogenic fibroblast cell lines using LTQ FT MS and GCMS techniques and software to describe the metabolic importance of the lack of two key enzymes (CDK4 and CDK6) in the cell cycle.
  • Chris Ricketts and Youfeng Yang - NCI SIRM studies of metabolic reprogramming in fumarate hydratase null cells
  • Pankaj Seth - Beth Israel Deaconess, Boston. SIRM analysis of LDH-A knockdowns in cancer cells.
  • Mariia Yuneva – University of California, San Francisco. Molecular regulatory mechanisms of the MYC oncogene in mammalian cells
  • Jack Hardwick-Oxford University. Structure of 5formylC modified DNA

Undergraduate

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Kathleen Marshall in Fan Lab
Undergraduate students participate in all aspects of research including conducting 
their own projects, developing analytical methods, and preparing platform and poster 
presentations.


Students mentored by Center faculty:
StudentDatesHome TownMentor
Alex BelshoffJune 2007-May 2008Louisville KYTeresa Fan
Sabine DhakalJune-Oct. 2007NepalTeresa Fan
Kathleen MarshallJune 2007-May 2008Leitchfield KYTeresa Fan
Mark Capece2008Davis CATeresa Fan
Ben King2008 Teresa Fan
Mabruk HabibSummer 2008 Andrew Lane
Martin McKinneySummer 2008 Andrew Lane
Sabrina Shatzman2009-2012 Teresa Fan
Gregory BousamraSummer 2010Louisville KYAndrew Lane
Zelalem MekonnenSummer 2011 Teresa Fan
Austin McCuistonSummer 2011 Andrew Lane
Laura Cornwell2011-2013Louisville, KYAndrew Lane
Connor Kinslow2013New York, NYAndrew Lane

Undergraduate Seminars

Center faculty give metabolomics presentations tailored specifically for undergraduate students to promote a broader dissemination of the field and what it has to offer for future scientific careers.
  • October 2007- North Eastern Illinois University: Andrew Lane " Biological Chemistry: Structure, Thermodynamics and Function "
  • Fall 2010 - Berea College: Dr. Teresa Fan presenting "Metabolism: Old or Gold?".
  • Fall 2010 - Huntingdon College: Dr. Hunter Moseley presenting "Metabolic Modeling of Converging Metabolic Pathways. Analysis of Non-Steady State Stable Isotope-Resolved Metabolomics of UDP-GlcNAc and UDP-GalNAc."
  • August 2011 - Summer Student Program, JG Brown Cancer Center: “Clinical Applications of Stable Isotope-Resolved Metabolomics (SIRM) in Non Small Cell Lung Cancer”. Andrew Lane
  • July 2012 - Summer Student Program, JG Brown Cancer Center: “Understanding Cancer Through Metabolism”. Andrew Lane

High School

High School students participate in many aspects of our metabolomics research efforts to promote early interest in science. Many use this opportunity for senior science projects and present their efforts at regional science fairs. 

Students mentored by Center faculty:
StudentGradeDateMentor
Doug LattimoreHigh SchoolMarch 12 2005Teresa Fan
Patrick OechsliJunior HighMarch 12 2005Teresa Fan
Li ZhangHigh SchoolMarch 11 2006Teresa Fan
Nambi ArumugamHigh SchoolMarch 11 2006Teresa Fan
Nambi ArumugamHigh SchoolFebruary 1 2007Teresa Fan
Monali HaldankarHigh SchoolFall 2008Andrew Lane
Anna DuanHigh SchoolFall 2008Andrew Lane
Anna DuanHigh SchoolFall 2010Andrew Lane
Justin BunchGroton Fellow2014Teresa Fan

Broader Community

Center faculty and staff have also participated in many local conferences with audiences ranging from secondary school teachers to environmentalists. These presentations serve to educate the community about the discipline of Metabolomics and offer the instructional services of the Center to the community it serves. The following is a partial list:
  • September 15, 2007 - Kentucky Association for Environmental Education: Metabolomics in bioavailability, mechanism, and biomarker discovery
  • November 2, 2007 - Kentucky Science Teachers Association: Metabolomics and Isotopomer analysis
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