Research Chemist —  Division of Biochemical Toxicology

William Tolleson, Ph.D.
(870) 543-7121
NCTRResearch@fda.hhs.gov  

Back to NCTR Principal Investigators page

 About  |  Publications  |  Lab Members
 

Background

Dr. William Tolleson received a bachelor's degree from the University of South Carolina in 1982 with a double major in chemistry and biology. He served as a chemistry laboratory shift supervisor/analytical chemist with General Nutrition Corporation before returning to the University of South Carolina where he received a Ph.D. in chemistry and biochemistry in 1990. He continued his training in cancer research as a postdoctoral fellow in the Department of Pathology at the University of South Carolina School of Medicine where he studied viral carcinogenesis. Dr. Tolleson joined NCTR in 1993 as a Veterans Administration Postdoctoral Fellow to study the mechanism-of-action of the foodborne carcinogen, mycotoxin fumonisin B1. He was converted to an NCTR staff fellow in 1996 and promoted to research chemist in 1997. He was awarded an FDA Commissioner’s Special Citation in 2008 for his work involving adulterated protein investigations. He was also awarded FDA Group Recognition Awards in 2008, 2012, and 2015 for his work related to pet-food and animal-feed contamination, shiga-like toxin research, and development of  agency-wide laboratory safety and inventory policies for hazardous biological agents and toxins.

Research Interests

A series of studies supported by the National Center for Food Protection and Defense (NCFPD) were performed by Dr. Tolleson’s research team in collaboration with the CFSAN Division of Food Processing Science and Technology (CFSAN/DFPST) to investigate the chemical and thermal inactivation of potential agents for bioterrorism in the presence of foods. In the first set of these studies, ricin thermal inactivation was investigated in the presence of several foods consumed by infants and toddlers, a subpopulation subject to increased risks for foodborne bioterrorism agents due to their small body size, immature immune systems, and their tendency to consume a single food as a meal. The influences of these foods on the kinetics and thermodynamics of ricin thermal inactivation were studied using biological and biophysical methods, including cell-based assays and differential scanning calorimetry.

Three additional NCFPD-sponsored collaborative studies were performed with CFSAN/DFPST. The stabilities of ricin and abrin in yogurt products from fermentation through refrigerated storage were evaluated. The biological activities of ricin and abrin were found to be inhibited by milk or yogurt and that both toxins were inactivated completely by batch-type pasteurization conditions.  The next evaluation was of the kinetics and efficiency for the inactivation of ricin and abrin on food-contact surfaces in the presence of dried food residues using chemical agents (sodium hypochlorite and peracetic acid) and commercial cleaning and sanitizing agents (phosphoric acid-based detergent, chlorinated alkali detergent, quaternary ammonium-based sanitizer, and peracetic acid-based sanitizer) approved for food-contact surfaces. They also performed experiments to determine if the results of the prior laboratory-scale studies addressing the thermal and chemical inactivation of ricin are applicable to commercial milk production using pilot-scale milk pasteurization equipment. 

The unique biochemical properties of ribosome-inactivating protein (RIP) toxins, such as ricin, abrin, and the shiga-like toxins, allowed Dr. Tolleson’s group to develop a novel, sensitive, and rapid method for their detection. The A-subunits of all RIP toxins share a common 28S rRNA-specific adenine glycosidase enzyme activity that inactivates ribosomes by removing an adenine from a specific site. The new method detects damaged 28S rRNA created by the adenine glycosidase activity of RIP toxins by detecting the altered TA nucleotide sequences introduced by reverse transcriptase into cDNA product strands with the speed, sensitivity, and selectivity typical for PCR.

Staphylococcal enterotoxin (SE) proteins exert toxicity via two biological activities ─ they induce emesis in the gastrointestinal tract and they are superantigenic, which can lead to lethal toxic shock. Like ricin and abrin, the classical SE isoforms SEA - SEE are also designated as bioterrorism Select Agents by HHS. The SE protein family has been expanded to include 18 recently discovered isoforms, some of which have been linked to food poisoning outbreaks. Unusual resistance to heat inactivation is a biochemical trait associated with the classical SE proteins. Molecular modeling studies supported by the FDA Medical Countermeasures Initiative are being performed to predict the heat-resistance properties of novel SE proteins and to determine kinetic and thermodynamic parameters for the thermal inactivation of novel SE isoforms in the presence of milk.

Consumption of products contaminated with hepatocarcinogenic pyrrolizidine alkaloids (PAs) are associated with liver cancer and veno-occulusive liver disease in humans and other mammals. Studies are being performed to determine if patterns of microRNA expression can be used as biomarkers of exposure to hepatocarcinogenic PAs. In a study to be supported by the FDA Office of Women’s Health, microRNA expression is being evaluated among patients diagnosed with systemic lupus erythematosus (SLE) and matched controls. This study is designed to determine if microRNA expression patterns can serve as a biomarker for SLE that is appropriate for patients of different sexes, races, ages, and disease status.

Professional Societies/National and International Groups

Agricultural and Food Chemistry Division/Functional Food and Natural Products Subdivision
Member
2007 – Present

American Association for the Advancement of Science
Member
1993 – Present

American Chemical Society
Member
2007 – Present

Chemical Toxicology Division, American Chemical Society
Member
2011 – Present

Institute of Food Technologists
Member
2009 – Present

International Association for Food Protection
Member
2012 – Present

Society of Toxicology
Member
2006 – Present  

Member, Food Safety Specialty Section
2008 – Present

Toxicology and Safety Evaluation Division
Member
2009 – Present

Selected Publications

Development of HepG2-Derived Cells Expressing Cytochrome P450s for Assessing Metabolism-Associated Drug-Induced Liver Toxicity.
Xuan J, Chen S, Ning B, Tolleson WH, Guo L.
Chem Biol Interact. 2016, 255:63-73.

MicroRNA hsa-miR-25-3p Suppresses the Expression and Drug Induction of CYP2B6 in Human Hepatocytes.
Jin Y, Yu D, Tolleson WH, Knox B, Wang Y, Chen S, Ren Z, Deng H, Guo Y, Ning B.
Biochem Pharmacol. 2016, 113:88-96.

MicroRNAs as Pharmacogenomic Biomarkers for Drug Efficacy and Drug Safety Assessment.
Koturbash I, Tolleson WH, Guo L, Yu D, Chen S, Hong H, Mattes W, Ning B.
Biomark Med. 2015, 9(11):1153-76.

Modulation of ALDH5A1 and SLC22A7 by microRNA hsa-miR-29a-3p in Human Liver Cells.
Yu D, Tolleson WH, Knox B, Jin Y, Guo L, Guo Y, Kadlubar SA, Ning B. 
Biochem Pharmacol. 2015, 98(4):671-80.

MicroRNA hsa-miR-29a-3p Modulates CYP2C19 in Human Liver Cells.
Yu D, Green B, Tolleson WH, Jin Y, Mei N, Guo Y, Deng H, Pogribny I, Ning B.
Biochem Pharmacol. 2015, 98(1):215-23.

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: the Role of the Extrapituitary Prolactin Promoter Polymorphism at -1149G/T.
Treadwell EL, Wiley K, Word B, Melchior W, Tolleson WH, Gopee N, Hammons G, Lyn-Cook BD.
J Immunol Res. 2015, 435658. doi: 10.1155/2015/435658. Epub 2015 Oct 25.

Ricin Detection: Tracking Active Toxin.
Bozza WP, Tolleson WH, Rosado LA, Zhang B.
Biotechnol Adv. 2015, 33(1):117-23. 

Toxicogenomics and Cancer Susceptibility: Advances with Next-Generation Sequencing.
Ning B, Su Z, Mei N, Hong H, Deng H, Shi L, Fuscoe JC, Tolleson WH.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2014, 32(2):121-58.

Metabolic Activation of Pyrrolizidine Alkaloids Leading to Phototoxicity and Photogenotoxicity in Human HaCaT Keratinocytes.
Wang CC, Xia Q, Li M, Wang S, Zhao Y, Tolleson WH, Yin JJ, Fu PP.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2014, 32(4):362-84.

Thermal Inactivation Reaction Rates for Ricin are Influenced by pH and Carbohydrates.
Zhang Z, Triplett OA, Nguyen KT, Melchior WB Jr, Taylor K, Jackson LS, Tolleson WH.
Food Chem Toxicol. 2013, 58:116-23.

Chemical Inactivation of Protein Toxins on Food Contact Surfaces.
Tolleson WH, Jackson LS, Triplett OA, Aluri B, Cappozzo J, Banaszewski K, Chang CW, Nguyen KT.
J Agric Food Chem. 2012, 60(26):6627-40.

Thermal Stability of Ricin in Orange and Apple Juices.
Jackson LS, Zhang Z, Tolleson WH.
J Food Sci. 2010, 75(4):T65-71.

A Functional Quantitative Polymerase Chain Reaction Assay for Ricin, Shiga Toxin, and Related Ribosome-Inactivating Proteins.
Melchior WB Jr, Tolleson WH.
Anal Biochem. 2010, 396(2):204-11.

Thermal Inactivation of Ricin Using Infant Formula as a Food Matrix.
Jackson LS, Tolleson WH, Chirtel SJ.
J Agric Food Chem. 2006, 54(19):7300-4.

Spontaneous Uveal Amelanotic Melanoma in Transgenic Tyr-RAS+ Ink4a/Arf-/- Mice.
Tolleson WH, Doss JC, Latendresse J, Warbritton AR, Melchior WB Jr, Chin L, Dubielzig RR, Albert DM.
Arch Ophthalmol. 2005, 123(8):1088-94.

Photodecomposition and Phototoxicity of Natural Retinoids
Tolleson WH, Cherng SH, Xia Q, Boudreau M, Yin JJ, Wamer WG, Howard PC, Yu H, Fu PP.
Int J Environ Res Public Health. 2005, 2(1):147-55.

Human Melanocyte Biology, Toxicology, and Pathology.
Tolleson WH.
J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2005, 23(2):105-61.

Metabolism of Biochanin A and Formononetin by Human Liver Microsomes In Vitro.
Tolleson WH, Doerge DR, Churchwell MI, Marques MM, Roberts DW.
J Agric Food Chem. 2002, 50(17):4783-90.

Apoptotic and Anti-Proliferative Effects of Fumonisin B1 in Human Keratinocytes, Fibroblasts, Esophageal Epithelial Cells and Hepatoma Cells.
Tolleson WH, Melchior WB Jr, Morris SM, McGarrity LJ, Domon OE, Muskhelishvili L, James SJ, Howard PC.
Carcinogenesis. 1996, 17(2):239-49.

Lab Members

Contact information for all lab members:
(870) 543-7121
NCTRResearch@fda.hhs.gov

Odbert Allen Triplett, M.S.
Biologist

Jeikun Xuan, Ph.D.
Visiting Scientist