Project description:<p>This is an evaluation of genetic associations with atazanavir (ATV) discontinuation for bilirubin-related causes within 12 months of treatment. Patients were treated at an HIV primary care clinic in Nashville TN from 1998 to 2012. A previously known SNP in UGT1A1 (rs887829) was used to define metabolizer genotypes (extensive, intermediate, slow metabolizer). Over 500,000 SNPs from genome-wide genotyping were used to define MDS (Multidimensional Scaling) coordinates to account for population stratification. Patients were defined as <b>cases</b> if they discontinued ATV for bilirubin-related causes within 12 months of treatment, otherwise they were defined as <b>controls</b> if they did not stop treatment.</p> <p>Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of black, 21.4% of Hispanic, and 8.6% of white patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 (95% C.I.: 1.7 to 31.5; p = 0.007). Among 152 white patients the HR was 14.4 (95% CI: 2.6 to 78.7; p = 0.002), but among 153 black patients the HR was 0.8 (95% C.I. 0.05 to 12.7; p = 0.87).</p>
Project description:We investigated the transcriptional responses of fasting against side effects of irinotecan chemotherapy in both tumor and healthy liver tissue
Project description:Antiretroviral therapy (ART) has revolutionized the clinical management of people with human immunodeficiency virus (HIV), transforming HIV infection into a chronic condition. Yet, the mechanisms of action and off-target effects of modern combination ART regimens versus individual ART medications are not fully understood. We found that ART regimens affected transcriptional signatures of genes involved in HIV-host PPIs and were less tied to common ART-related side effects. Our findings support the use of high-throughput transcriptomics to detect specific mechanisms of ART on- and off-target effects to help prioritize new drug targets and compounds in future development and optimization of safer and more efficient ART.
Project description:To gain an insight into the molecular mechanisms by which bilirubin induces toxicity, we exposed human MCF7 and SHSY5Y cell lines to 50 uM bilirubin (which equates to 6.39 uM of unconjugated bilirubin) for 4 hours. The cells were then washed with PBS and the RNA extracted using Tri-Reagent/1-bromo-3-chloropropane phase separation. The data was extracted using GenomeStudio and normalized/analyzed using ArrayTrack.