The candidate was trained as an immunologist and became interested in the effects of ethanol (EtOH) on the immune system while on Sabbatical Leave at the Medical College of Virginia. The major focus of the candidate's laboratory is to determine the role of endogenous corticosterone in EtOH- induced suppression of humoral immune responses in a mouse model for binge drinking. This work is funded by NIH for three years. In addition, the candidate has a cooperative agreement with EPA to develop statistical models to predict host resistance to infection or cancer on the basis of easily measured immunological parameters. The applicant also has experience and interest in the effects of pesticides on the immune system and plans to pursue funding to study interactions between the effects of EtOH and pesticides on the immune system. A long-term goal of the applicant's research is to relate the molecular and cellular mechanisms by which EtOH affects the immune system to its effects on host resistance to infection or cancer. An RSDA would provide invaluable assistance in reaching these research goals, because it would decrease the candidate's non-research activities from their current level of 45% effort to 19%. The institution's development plans for the candidate include encouraging continued scientific collaboration with several senior-level scientists on campus and at other institutions. In addition, the institution has developed a detailed plan by which an RSDA would be used to allow the applicant the time needed for full development of his research career with no negative impact on other faculty members or on the quantity or diversity of instruction at the institution. Mississippi State University is ranked in the top 100 research universities in the U.S., and the 23 faculty members in the Department of Biological Sciences have secured over $3,000,000 in research funding from 11 different agencies or companies during the past year. However, the Department also has a substantial undergraduate teaching and advising responsibilities. An RSDA would be an ideal solution for this candidate, because it would relieve him of many of his duties in this area and allow him to develop fully as a researcher. The candidate's research during the RSDA will focus on the effects of EtOH on humoral immune responses in a mouse model for binge drinking. Although binge drinking is a common behavior in humans, its potential impact on the immune system has not been extensively investigated. The project proposed is the same as in the candidate's recently funded R01 application. It is designed to test the following HYPOTHESIS: A single dose of ethanol by gavage suppresses T-dependent primary humoral immune responses in B6C3F1 female mice by mechanisms that are predominantly glucocorticoid-dependent. This hypothesis is based on preliminary data, some of which have now been published.
Specific aims are proposed that will provide several independent lines of evidence that should confirm or refute this hypothesis. An overview of plans for a competing continuation project is included. This continuation project is based on preliminary data indicating substantial suppression of cytokine gene expression in the spleens of EtOH-treated mice. These data suggest that EtOH may shift the balance between T helper type 1 and T helper type 2 cells. This would have important effects on the immune system. The experiments planned to investigate this issue should provide important new information about the role of endogenous glucocorticoids in regulating the balance between Th1 and Th2 cells.
| Crittenden, P L; Carr, R; Pruett, S B (1998) Immunotoxicological assessment of methyl parathion in female B6C3F1 mice. J Toxicol Environ Health A 54:1-20 |
| Wu, W J; Pruett, S B (1997) Involvement of catecholamines and glucocorticoids in ethanol-induced suppression of splenic natural killer cell activity in a mouse model for binge drinking. Alcohol Clin Exp Res 21:1030-6 |
