Medical Students 
Graduate Medical Education
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Carol
Gilchrist
Degree(s): PhD Graduate School: Univ of Western Ontario Primary Appointment: Assistant Professor, Medicine, Infectious Diseases and International Health Research Interests: My long-term goal is to identify the genetic program required to cause amebic colitis. My studies have focused on defining factors that control virulence and the outcome of infection. Email Address: cg2p@Virginia.EDU |
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Research Description Entamoeba histolytica, the causative agent of amebiasis, is prevalent in areas of poor sanitation. For example, E. histolytica infection was detected in 80% of the children from an urban slum in Dhaka, Bangladesh (40% per annum). The consequences of a new E. histolytica infection are unpredictable. Not only does disease occur in only a minority of infections (20%), but an initially asymptomatic infection can result in future invasive disease (~12.5%). Patients can present with liver abscess years after travel to an endemic area. While human genetics, environmental conditions, and parasite genotype influence the infection outcome, these factors don’t account for the majority of differential susceptibility. Only a ~two fold increase in E. histolytica infections occurred in malnourished children, or children lacking the protective HLA class II DQB1*0601 allele. It is remains puzzling why only some infections with E. histolytica result in disease. The variable outcome of infection and latent period between colonization and disease suggests that adaption of the parasite to the host via altered gene expression could contribute to the virulent phenotype. In this application we will focus on the hypothesis that parasite regulation of virulence factor gene expression is responsible for the switch from asymptomatic colonization to invasive disease. The transcription factor URE3-BP is known to regulate the expression of two known amebic virulence genes, the Gal/GalNAc adherence lectin and ferredoxin. Over-expression of a dominant positive version of the URE3-BP protein alters the expression of a subset of genes and produces a more a virulent phenotype. Understanding the broader role of this regulatory factor in virulence will help define the genetic program that is required for invasion of the host, identify new biomarkers of disease progression, and lead to a better understanding of the parasite factors that contribute to invasive disease. Selected Publications Intranet Profile
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