ADH Genotype ALC Abuse & Cell Response to V. vulnificus

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The interactions between environmental host pathogen are extremely complex, and require a multi-disciplinary approach to understand the interrelationships within this paradigm at a mechanistic level. </p>
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The candidate, an environmental microbiologist, proposes to fully integrate didactic training in molecular and applied epidemiology with mentored basic research. It is the goal of the candidate to gain the necessary training to allow, not only the investigation of specific parts of these interactions through applied research, but to develop a career path that will allow a vision of the paradigm as a whole. </P>
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Through the Masters Degree program in the Department of Epidemiology and Preventive Medicine at the University of Maryland, Baltimore, the candidate will gain new and enhanced skills in molecular and applied epidemiology, biostatistics, clinical study design, and data analysis. The commitment and participation of three mentors, together with strong institutional support ensures that the candidate is in the ideal environment for career development through completion of the proposed training and by conducting highly relevant environmental biomedical research. </P>
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In the research component of the proposal the candidate will use molecular epidemiology techniques to investigate whether there is an association between host alcohol dehydrogenase (ADH) genotype, alcohol abuse, immune status and cellular response to environmental food-borne pathogen Vibrio vulnificus. </P>
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Individuals that abuse alcohol are at increased risk of developing septicemia and cytokine-mediated shock following exposure to V. vulnificus in raw oysters. However, not all individuals with the same (perceived) risk factors develop disease from exposure to V. vulnificus. Differences in host susceptibility may lie at the genetic level, as suggested for other infectious diseases such as HIV. </P>
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Alcohol metabolites, particularly acetaldehyde, can directly affect immune cells, cause immunosuppression and therefore affect the response to pathogens. Alcohol metabolism is controlled by ADH whose gene polymorphisms have been shown to affect alcohol metabolic rates. </P>
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The investigators hypothesize that particular ADH genotypes are associated with cellular oxidative stress in the presence of alcohol abuse, an increased inflammatory cytokine response, and an adverse response to V. vulnificus. Studies will include both genetic and cellular endpoints to investigate the effects of an environmental exposure on host immune response and susceptibility to an environmental bacterial pathogen.</P>