EDWIN L. THOMAS, M.S., Ph.D.
Bioscience Research Department
429 Boling Center For Developmental Disabilities
- PostDoc, Roche Institute of Molecular Biology, Molecular Biology
- Ph.D., University of Michigan, Ann Arbor, Michigan, Biological Chemistry
- M.S., University of Michigan, Ann Arbor, Michigan, Biological Chemistry
- A.B., Miami University, Oxford, Ohio, Chemistry
Alpha- and beta-defensins.
Urokinase plasminogen activator (uPA).
Plasminogen activator inhibitor-1 (PAI-1).
Plasminogen activator receptor (PAR).
Saliva and the Prevention of Oral Disease. Human saliva contains proteins and peptides that inhibit growth of micro-organisms. These natural antibiotic substances are produced and secreted by the salivary glands. A family of histidine-rich peptides known as histatins helps to prevent oral fungal infections, while the enzyme lactoperoxidase helps to prevent infections by many bacteria. Goals of this project are to learn how these saliva components block microbial growth, how pathogenic micro-organisms become resistant to these protective substances, and how these natural defenses can be increased to prevent dental caries and infection of oral tissues.
Leukocytes and Inflammation. Neutrophils are white blood cells that protect the body against infection by killing invading viruses, fungi, and bacteria. Neutrophils migrate through the blood vessel walls and into the tissues in response to chemical signals released at sites of infection and inflammation. In healthy individuals, about one million neutrophils per minute migrate through the oral tissues and are shed into the mouth through the gingival crevices. Neutrophils release proteins, peptides, and oxidizing agents that kill micro-organisms, but these toxins can also damage human tissues. Goals of this project are to learn identify the toxins, determine how they kill micro-organisms, and learn how the body protects itself against these toxins.
Tumor Biomarker Proteins
Changes in the pattern of protein expression by tumor cells provide molecular fingerprints that allow early detection of the tumor and evaluation of tumor properties that reflect the stage of tumor progression, drug resistance, and the potential for tissue invasion and metastatic spread. Advances in proteomics have made it possible to analyze complex biological systems to detect differences in protein expression that may prove to be clinically useful biomarkers for early detection of disease and selecting the best therapy for each patient based on properties of the tumor cells. Proteomic analysis of cell extracts and serum-free conditioned media from multiple cultures of tumor cells and normal tissue cells is used to detect and identify proteins that differ in expression and have a correlation with tumor cell properties. Two-dimensional isoelectric focusing and SDS gel electrophoresis (2-DG) is followed by densitometry to detect and match protein spots and compare their staining intensity. Spots with adequate intensity and separation from adjacent spots are excised and the proteins identified by sequencing of tryptic peptides by mass spectrometry. Proteins from the list of candidate biomarkers are selected for validation by immunochemical methods. Antibodies are used to immunolocalize the protein in fixed, adherent cells to confirm that the protein is detectable, detect differences in intracellular location, and obtain a semi-quantitative estimate of protein expression. Immunoblotting of gels is used to detect all immunoreactive forms of the protein and determine whether differences in total protein expression or post-translational modifications account for differences detected by 2-DG. The goal is to identify and validate a panel of protein biomarkers that are related to differences in tumor cell properties. These studies will accelerate the process of developing clinically useful biomarkers for early cancer detection and selecting the best treatment for each patient based on tumor properties.
Antimicrobial peptides of saliva, leukocytes, and epithelial cells.
Peroxidase enzymes of leukocytes and saliva.
Proteomics and biomarkers of human disease.
Calcium-binding molecules and resistance of the teeth to damage by acid.
Lecture topics include:
Membrane transport and bioenergetics
Lipids and lipoproteins
Biological membrane structure and function
Saliva composition and function
- Dabbous, MK, Jefferson, MM, Haney, L, Thomas, EL. Biomarkers of metastatic potential in cultured adenocarcinoma clones. Clinical and Experimental Metastasis, 28, 101-111, 2011.
- Thomas, EL, Dabbous, MK, Gilpatrick, RO. The Hinman Student Research Symposium. Journal Tennessee Dental Association, 86, 43-45, 2006.
- Tipton, DA, Pabst, MJ, Thomas, EL, Babu, JP, Stein SH, Fry H. Association of high plaque levels of Prevotella intemedia with aggressive periodontitis in a 16-year old female. PERIO - Periodontal Practice Today, 3, 115-122, 2006.
- Thomas, EL, Jefferson, MM, Learn, DB, King, CC, Dabbous, MK. Myeloperoxidase-catalyzed chlorination of histamine by stimulated neutrophils. Redox Rep, 5 (4), 191-6, 2000.
- King, CC, Jefferson, MM, Thomas, EL. Secretion and inactivation of myeloperoxidase by isolated neutrophils. J Leukoc Biol, 61 (3), 293-302, 1997.
- Thomas, EL, Bozeman, PM, Jefferson, MM, King, CC. Oxidation of bromide by the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase. Formation of bromamines. J Biol Chem, 270 (7), 2906-13, 1995.
- Thomas, EL, Milligan, TW, Joyner, RE, Jefferson, MM. Antibacterial activity of hydrogen peroxide and the lactoperoxidase-hydrogen peroxide-thiocyanate system against oral streptococci. Infect Immun, 62 (2), 529-35, 1994.
- Thomas, EL, Jefferson, MM, Joyner, RE, Cook, GS, King, CC. Leukocyte myeloperoxidase and salivary lactoperoxidase: identification and quantitation in human mixed saliva. J Dent Res, 73 (2), 544-55, 1994.
- Bozeman, PM, Learn, DB, Thomas, EL. Inhibition of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase by dapsone. Biochem Pharmacol, 44 (3), 553-63, 1992.
- Thomas, EL, Bozeman, PB, Learn, DB. Lactoperoxidase: structure and catalytic properties. Peroxidases: Chemistry and Biology, 1, 123-142, 1991.
- Thomas, EL, Learn, DB. Myeloperoxidase-catalyzed oxidation of chloride and other halides: the role of chloramines. Peroxidases: Chemistry and Biology, 1, 83-104, 1991.
- Learn, DB, Fried, VA, Thomas, EL. Taurine and hypotaurine content of human leukocytes. J Leukoc Biol, 48 (2), 174-82, 1990.
- Bozeman, PM, Learn, DB, Thomas, EL. Assay of the human leukocyte enzymes myeloperoxidase and eosinophil peroxidase. J Immunol Methods, 126 (1), 125-33, 1990.
- Learn, DB, Thomas, EL. Inhibition of tumor cell glutamine uptake by isolated neutrophils. J Clin Invest, 82 (3), 789-96, 1988.
- Thomas, EL, Lehrer, RI, Rest, RF. Human neutrophil antimicrobial activity. Rev Infect Dis, 10 Suppl 2, S450-6, 1988.
- Thomas, EL, Learn, DB, Jefferson, MM, Weatherred, W. Superoxide-dependent oxidation of extracellular reducing agents by isolated neutrophils. J Biol Chem, 263 (5), 2178-86, 1988.
- Thomas, EL, Jefferson, MM, Bennett, JJ, Learn, DB. Mutagenic activity of chloramines. Mutation Research, 188, 35-43, 1987.