John B. Barnett

Academic Interests:

The work in our laboratory focuses on the consequences to the immune system of exposure to xenobiotic compounds. It is our goal to utilize their known immunomodulatory effects to assist in understanding the basic biology of the immune cells. Two projects are currently in progress in our laboratory: a prenatal exposure model involving an herbicide, atrazine; and an adult exposure model studying the effects of the herbicide, propanil. Prenatal exposure to atrazine results in a reduction of B and T cell activity. Because of the apparent permanence and subtlety of the atrazine-induced immunotoxicity, it is critical to determine the mechanism(s) of these effects and we are currently focused on in vitro studies on cytotoxic T cell (CTL) and natural killer (NK) cell activity by examining the molecular events involved in CTL and NK cell activation and cytokine production.

Our second project studies the effects of propanil, a post-emergent herbicide, on the immune response of adult mice. Propanil causes modifications to T cell and macrophage cytokine production as well as a reduction of the in vivo immune response to several types of antigens. Therefore, we are studying the effects of propanil on cytokine production at the molecular level to increase our understanding of T-cell and macrophage activation events. We have discovered that propanil down regulates the activation of two important transcription factors, NF-kappaB and AP-1. The mechanism of how propanil accomplishes this effect is currently under study by focusing on the signaling pathways that are responsible for the activation of these transcription factors.

Publications:

Jiang, B-H., Ling-Zhi Liu, Rosana Schafer, Daniel C. Flynn, and John B. Barnett. 2006. A novel role for 3,4-dichloropropionanilide (DCPA) in the inhibition of prostate carcinoma cell migration and hypoxia-inducible factor 1-alpha expression, BMC Cancer 6:204.

Salazar, K.D., M. Miller, J. B. Barnett, and R. Schafer. 2006. Evidence for a novel endocrine disruptor: The pesticide propanil requires ovaries and steroid synthesis to enhance humoral immunity. Toxicol. Sc. 93:62-74.

Rowe, A.M., K.M. Brundage, R. Schafer and J.B. Barnett. 2007. In vitro atrazine-exposure inhibits human natural killer cell lytic granule release. Toxicology and Applied Pharmacol 211(2):179-188

Ustyugova, I., L. Frost, K. VanDyke, K. Brundage, R. Schafer and J.B. Barnett. 2007. 3,4-dichloropropionaniline suppresses normal macrophage function. Toxicological Sc. 97(2):364-374.

Rowe, A.M., K.M. Brundage, and J.B. Barnett. 2008. Developmental Immunotoxicity of Atrazine in Rodents. Basic and Clinical Pharmacol Toxicol 102:139-145

Klinke, David J II; Irina V Ustyugova; Kathleen M Brundage; and John B Barnett. Modulating Temporal Control of NF-kappaB Activation: Implications for Therapeutic and Assay Selection. Biophysical Journal, in press