Adjunct Associate Professor in the Department of Pediatrics
My laboratory is involved in the study of Hepatitis C virus pathogenesis. We initially began by studying alterations in lipid metabolism and steatosis. We have recently shifted to examine the role of the Hedgehog pathway in HCV permissiveness. We found that Huh7.5 cells, which are highly permissive for HCV replication, have very high levels of Hedgehog pathway activity and also have higher expression of mesenchymal markers. This is in sharp contrast to most hepatocytes which have low levels of Hedgehog pathway acitivty and predominatly epithelial expression markers.. We have also used different pharmacologic agents to increase or decrease Hedgehog pathway activity and observed the corresponding effect on HCV replication. These facts support the idea that HCV may perferentially replicate in a limited number of liver cells with increased Hedgehog activity that possess a less differentiated phenotype. We are actively studying the key cellular proteins that may mediate this process.
Another line of research in the lab is probing the intracellular determinants of HCV vertical transmission. We are examining key steps of the intracellular life cycle of HCV that have been identified in hepatocytes and using placental cell lines to investigate their suitability for sustaining/propagating HCV infection. Our preliminary work indicates that HCV Core protein may be processed differently in placental cells, which we hypothesize may serve as a major block to new virus production. We are initiating collaborations with investigators in Egypt to obtain placental tissue to perform additional studies to detect evidence of HCV replication in placental tissue.
This work is being conducted in close proximity to the core liver research labs, run by Anna Mae Diehl, chief of Gastroenterology/Hepatology here at Duke.
I also have clinical research interests.
One is the impact of Hepatitis C in infants and children. I am particularly interested in the determinants of vertical transmission and the factors for resolution in HCV infection in young children. We have begun a study examining the immune response in pregnant women with HCV and their infants to understand the dynamics of responses in the ante-, peri- and post-partum periods.
Two is the outcomes of children under 3 years old that present with fever to the urgent and emergent care centers. Since the universal administration of Pneumococcal conjugate vaccine in 2000, there has been a significant drop in the rates of invasive penumococcal disease. Our focus has been to re-evaluate the clinical paradigm in febrile children that calls for a complete laboratory evaluation and empiric antibiotics. Our data thus far shows that all interventions except for urine cultures are no longer needed. We will continue to evaluate for changes in this group.
Third is the investigation of increasing resistance patterns in E. coli infections in Pediatric patients. A significant rise in TMP/SMX resistance has occured over the last 5 years that appreas to correlate with the rise in TMP/SMX prescriptions for MRSA disease. We are investigating the nature of this relationship.
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