U.S. Department of Energy

Pacific Northwest National Laboratory

Tom Metz

Tom_Metz's picture
Biography:

I received my PhD in Chemistry in the Department of Chemistry and Biochemistry at the University of South Carolina with Dr. John W. Baynes, who studied the role of the Maillard reaction in the development of diabetic complications and in aging. Originally discovered by the French scientist, Louis-Camille Maillard (1878-1936), Maillard chemistry involves non-enzymatic reactions between nucleophilic groups (e.g. α- and ε-amines, thiols) of amino acids on proteins and reducing sugars and/or peroxidized lipids. 

The reaction is catalyzed by heat, and products of Maillard chemistry form and accumulate in cooked food and contribute to its texture, flavor, and aroma. From its discovery until the late 1970s, the Maillard reaction remained the domain of food chemists. It was at this time that products of Maillard chemistry were identified in vivo, including in humans. After all, as John Baynes likes to say, humans are essentially low-temperature ovens with long cooking cycles. Because Maillard chemistry involves non-enzymatic modification of proteins by reducing sugars, such as glucose, individuals with chronically high levels of blood glucose (i.e. those with diabetes mellitus) accumulate Maillard products on tissue proteins to a greater extent and at a faster rate than those individuals with normal blood glucose levels. One protein modification in particular, glycated hemoglobin, is now used as a marker of long term glucose control in individuals with diabetes. The Maillard hypothesis of diabetic complications states that chronic, cumulative chemical modification of tissue proteins by glucose, and also by oxidized lipids, alters their structure, turnover, and function, ultimately leading to diabetic nephropathy, retinopathy, neuropathy, and cardiovascular disease. My PhD research in the Baynes lab focused on the quantification of Maillard reaction intermediates trapped by pyridoxamine, a vitamer of B6, in biofluids of treated, diabetic animals using liquid chromatography-mass spectrometry (LC-MS) and isotope dilution.

My post-doc was performed in the area of separations coupled wtih mass spectrometry under the mentorship of Dick Smith at Pacific Northwest National Laboratory (PNNL) with a major focus on metabolomics and minor focus on proteomics. At the time, metabolomics was the latest and least mature (and still is) of the systems biology sciences, and my charge was to bring metabolomics measurement capabilities to a predominately proteomics research group. I initially explored the combination of high pressure, high peak capacity capillary LC separations coupled with FTICR MS and demonstrated that many features (characterized by measured m/z and retention times) could be detected in analyses of a variety of sample types. However, the confident identification (see Sumner et al., Metabolomics, 2007 for guidelines from the Metabolomics Standards Initiative regarding metabolite identification confidence) of large numbers of metabolites in LC-MS data remained elusive, as resources such as Metlin, HMDB, etc were not yet available. For the remainder of my post-doc, I continued to apply LC-MS in metabolomics analyses, eventually also expanding to lipidomics. In additon to my work in metabolomics/lipidomics, I continued to study aspects of diabetes mellitus, including both the role of the Maillard reaction, as well as searching for novel protein or metabolite/lipid markers of both types 1 and 2 diabetes.

Currently, I am the metabolomics technical lead in the Integrative Omics group at PNNL and the Team Lead for a group of scientists that focuses on applications of high throughput proteomics, metabolomics, and lipidomics methods to various biological questions. My research has focused on the development of both global and targeted metabolomics and lipidomics capabilities based on LC and gas chromatography (GC) coupled with mass spectrometry, both for fundamental studies of metabolism/metabolic interactions as well as for biomarker discovery. In addition, I maintain my interest in the Maillard reaction in the context of diabetic complications, and have become involved in various efforts to identify novel biomarkers of both types 1 and 2 diabetes.

Current projects include:

  • The NIAID-funded Omics - Lethal Human Viruses: Proteomics, Metabolomics, and Lipidomics Core. Our core performs mass spectrometry-based omics analyses of cell and mouse models of viral infection, including influenza, West Nile, MERS, and Ebola viruses. Samples are generated at collaborating laboratories, chemically inactivated using the MPLEx protocol, and then shipped to our laboratory for analysis.
  • The NIDDK-funded BetaMarker project. BetaMarker is a multi-PI project within the Consortium on Beta Cell Death & Survival (CBDS) of the Human Islet Research Network, and its goals are to 1) test existing candidate beta cell-specific protein and nucleic acid biomarkers in human samples from the DPT-1 and TrialNet PTP cohorts, and 2) perform comprehensive proteomics and functional genomics analyses to discover new beta cell-specific biomarkers that will be funneled back into testing in human populations.
  • The NIDDK-funded Proteomics Laboratory for The Environmental Determinants of Diabetes in the Young program. In this project, we are performing blinded proteomics analyses of children enrolled in TEDDY who have developed autoimmunity, as well as those who have progressed to clinical type 1 diabetes. The goal of the project is to identify proteins in the blood that characterize the autoimmune reponse and that may be indicative of ongoing beta cell loss.
  • The NIH Common Fund-funded Undiagnosed Diseases Network Metabolomics Core. A very challenging project, we are performing untargeted metabolomics and lipidomics analyses of individuals enrolled in the UDN and whose disease has evaded diagnosis. These patients have undergone most types of clinical analyses for inborn errors of metabolism with negative results. Our goal is to associate patient metabolite and lipid profiles with gene sequencing and phenotype data, contributing towards a diagnosis.
  • The PNNL Microbiomes in Transition Initiative-funded Deciphering Microbiomes through Metabolites project. In this project, we are developing advanced metabolomics methods and capabilities geared towards comprehensive, chemical identification of metabolites in soil and gut microbiomes. Specific foci include incorporation of ion mobility spectrometry and the physical-chemical property of collison cross section in metabolomics workflows, and the development of pipelines for metabolite enrichment and structural characterization by NMR.

 

The HIRN CBDS group. Photo taken nduring the 2016 HIRN Anual Investigator Meeting, Hyatt Regency Hotel, Bethesda, MD.