The underlying theme of the Mass Spectrometry Group´s research efforts is the structural characterization of biomolecules involved in the body´s immunological and inflammatory responses to environmental exposures. As the immune system is challenged, a number of different innate and adaptive immunological responses can occur. These responses include complement activation, production of antibodies, regulation of protein levels and activities, changes in levels of pro- or anti-inflammatory small molecules, and complement activation. Each of these responses is regulated by additional levels of complexity where multiple events occur, including the recruitment of protein partners, synthesis of second messengers, posttranslational modifications (PTMs) of proteins, and repair of biological damage. The group is especially interested in mass spectrometric-based structural studies of the specific biomolecules involved in these cellular events. To address these questions, the group uses techniques such as nanoscale capillary liquid chromatography, direct analysis of affinity-bound analytes by MALDI/MS, that the group was instrumental in their development. Broadly categorized, these studies include: the characterization of the primary sequence, PTMs, and tertiary structures of relevant proteins, the determination of the recognition surfaces involved in protein:protein interactions, and small molecule quantitation.
Major areas of research:
Structural studies of proteins and protein:protein interactions associated with pathogens and the body's immune response and with autoimmunity.
Structural studies of environmental damage to proteins, especially free-radical initiated oxidative stress, and of proteins involved in repair of damage of damaged DNA.
Identification of PTMs and changes in PTMs (e.g. phosphorylation) of proteins, especially as it relates to cell signaling and protein regulation in response to environmental exposures.
Identification of changes in protein expression and levels of expression in response to environmental exposures.
Quantitation of small molecules as they relate to diseases and physiological responses.
Mapping epitopes recognized by human anti-HIV gp120, gp41 and p24 protein antibodies, human anti-HCV E2 protein antibodies, anti-B. anthracis ATR protein antibodies
Development of oxidative surface mapping for characterization of protein recognition surfaces
Structural characterization of proteins and protein:protein interactions involved in DNA repair, Sjogren’s disease, B. subtilis competency, and (blood clotting) Factor Xa
Development of novel methods. e.g., TiO2 metal ion affinity, for isolation and characterization of phosphorylated proteins and peptides
Development of improved methods for the quantitative analysis of androgens by LC/MS/MS and their application to refractory prostate cancer tissue
Quantitation of eicosanoids in a variety of tissue types
Kenneth B. Tomer, Ph.D., is the head of the Mass Spectrometry Group. He has authored more than 200 peer-reviewed research papers and more than 30 reviews and book chapters. He earned a B.S. in chemistry from Ohio State University and a Ph.D. in organic chemistry from the University of Colorado in 1970. Prior to joining NIEHS in 1986, he was Associate Director of the Midwest Center for Mass Spectrometry/Assoc. Research Professor, Department of Chemistry, University of Nebraska.