Our environmental toxicology research program explores the relationships between biological organisms and their responses to chemical contaminants. The lab’s focus is on developmental toxicology, utilizing tools from immunotoxicology and neurotoxicology to ascertain and evaluate the responses of individual organisms to toxicant exposures. A variety of compounds affect immune, nervous, and reproductive function if exposure occurs during development; therefore, our goal is to understand upstream events that might influence the function of more than one system. These types of studies will help us to understand how toxicants exert developmental effects on biological organisms.

Our main research interests are:

1)      Exploring effects of environmental toxicants on immune function in adult organisms exposed during development. Evaluating immune function allows us to ask “is the immune system doing what it is asked?” We use a variety of functional tests to assess adaptive and innate immunity; such tests are reliable predictors of immunotoxicity and allow us to begin the process of backtracking to modes or mechanism of action at the cellular, molecular, and genetic levels that lead to change in function.

2)      Exploring the developmental relationships between the immune system and the nervous system. Specifically, we are interested in how exposure to developmental immunotoxicants leads to changes in nervous system function that may occur via common mechanisms of action. Developmental immunotoxicity (DIT) occurs when the developing immune system experiences an adverse outcome after exposure to a toxicant or other stressor. Exposure to developmental immunotoxicants has been suggested in several neurological disorders, including autism and autism spectrum disorder, chronic fatigue syndrome, and mental retardation, and possibly plays a role in disease susceptibility in aging populations.

Our recent work has centered on immune system effects of perfluorooctanoic acid (PFOA), a fluorinated compound with myriad industrial and commercial applications that is of regulatory concern to the U.S. Environmental Protection Agency. Our data indicate that T-dependent antibody responses are suppressed in adults exposed to PFOA for only 15 days. We are currently exploring differences in host phenotype, corticosterone production, and the role of the peroxisome proliferator activated receptor alpha (PPARα) as potential mechanisms of this suppression. We are also evaluating immune responses in offspring developmentally exposed to PFOA as several studies suggest that PFOA is a developmental toxicant.

In addition to understanding the immunotoxicity of PFOA, we are developing models for evaluating neurological responses after exposure to developmental immunotoxicants. 

 

Selected publications:

 

Papers

Whalen MM, DeWitt JC, Luebke RW.  2008. Serum supplementation modulates the effects of dibutyltin on human natural killer cell function. Toxicological Sciences, 104:312-319.

 

DeWitt JC, Copeland CB, Strynar MJ, and Luebke RW.  2008. Perflurooctanoic acid-induced immunomodulation in adult C57BL/6J or C57BL/6 female mice. Environmental Health Perspectives. 116:644-650.

 

DeWitt JC, Copeland CB, and Luebke RW. 2008. An organotin mixture found in polyvinyl chloride (PVC) pipe is not immunotoxic to adult Sprague-Dawley rats. Journal of Toxicology and Environmental Health Part A. 71:276-282.

 

DeWitt JC, Copeland CB, and Luebke RW. 2007. Immune function in Sprague-Dawley rats exposed to dimethyltin dichloride in drinking water during development or adulthood. Toxicology. 232:303-310.

 

Lim J, DeWitt JC, Sanders RA, Watkins JB III, and Henshel DS. 2007. Suppression of endogenous anti-oxidant enzymes by 2,3,7,8-tetrachlorodibenzo-p-dioxin-Induced oxidative stress in chicken liver during development. Archives of Environmental Contamination and Toxicology. 52:590-595.

 

DeWitt JC, Copeland CB, and Luebke RW. 2006. Developmental exposure to 1.0 or 2.5 mg/kg of dibutyltin dichloride does not impair immune function in Sprague-Dawley rats. Journal of Immunotoxicology. 3:245-252.

 

DeWitt JC, Millsap DS, Yeager RL, Heise SS, Sparks DW, and Henshel, DS. 2006. External heart deformities in passerine birds exposed to environmental mixtures of polychlorinated biphenyls during development. Environmental Toxicology and Chemistry. 25(2):541-551.

 

DeWitt JC, Copeland CB, and Luebke RW. 2005. Immune responses in sprague-dawley rats exposed to dibutyltin dichloride in drinking water as adults. Journal of Immunotoxicology. 2:151-160.

 

DeWitt JC, Meyer EB, and Henshel DS. 2005. Environmental toxicity studies using chickens as surrogates for wildlife: Effects of vehicle volume. Archives of Environmental Contamination and Toxicology. 48:260-269.

 

DeWitt JC, Meyer EB, Watkins JB, and Henshel DS. 2005. Environmental toxicity studies using chickens as surrogates for wildlife: Effects of day of injection. Archives of Environmental Contamination and Toxicology. 48:270-277.

 

Stanton B, DeWitt J, Henshel D, Watkins S, and Lasley B. 2003. Fatty acid metabolism in neonatal chickens (Gallus domesticus) treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 3,3’,4,4’,5-pentachlorobiphenyl (PCB-126) in ovo. Comparative Biochemistry and Physiology C - Pharmacology and Toxicology, 136:73-84.

 

Henshel DS, Martin JW and DeWitt JC. 1997. Brain asymmetry as a potential biomarker for developmental TCDD intoxication: A dose-response study. Environmental Health Perspectives. 105:2-11.

 

Henshel DS, Martin JW, Norstrom RJ, Elliot J, Cheng KM and DeWitt JC. 1997. Morphometric brain abnormalities in double-crested cormorant chicks exposed to polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls. Journal of Great Lakes Research. 23:11-26.

 

Book Chapters and Reviews

DeWitt JC, Shnyra A, Badr MZ, Loveless SE, Hoban D, Frame SR, Cunard R, Anderson SE, Meade BJ, Peden-Adams MM, Luebke RW, and Luster MI.  Immunotoxicity of perfluorooctanoic acid and perfluorooctane sulfonate and the role of peroxisome proliferator activated receptor alpha. Submitted to Critical Reviews in Toxicology (in press).

 

Luebke RW, Beamer CA, Bowman C, DeWitt J, Gowdy K, Johnson VJ, Shepherd DM, and Germolec DR. Immunotoxicology. In: General and Applied Toxicology, 3^rd Edition (MB Silva, Ed.), John Wiley & Sons, West Sussex, UK, pp. xx. 2008.

 

Luebke RW and DeWitt JC. Aging and the Immune System. In: Comprehensive Toxicology, 2nd Edition (Ed.), Elsevier Limited, Oxford, UK, pp. xx. 2008.

 

Henshel DS, DeWitt JC, and Troutman, A. Using chicken embryos for teratology studies. In: Current Protocols in Toxicology (M.D. Maines, L.G. Costa, E. Hodgson, D.J. Reed, and I.G. Sipes, Eds.), Supplement 14, pp. 13.4.1-13.4.19. 2002.