Project description:Whole exome sequencing was performed to explore the mutational landscape and potential molecular signature of HPV-positive versus HPV-negative OAC. Four hr-HPV-positive and 8 HPV-negative treatment-naive fresh-frozen OAC tissue specimens and matched normal tissue were analysed to identify somatic genomic mutations
Project description:Griffithsin (GRFT) is an anti-viral lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after topical administration, and lack of cross-resistance with existing products prompted its development for topical HIV pre-exposure prophylaxis. We evaluated safety, pharmacokinetics and pharmacodynamics of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy, HIV-negative, non-pregnant women following once daily vaginal gel administration for 14 days. No significant adverse events, histopathological changes in cervico-vaginal mucosa, or anti-drug (GRFT) antibodies were detected. No cervicovaginal proinflammatory responses and no changes in the ectocervical transcriptome were evident. Vaginal microbiome remained largely unchanged. Reduced abundance of vaginosis-associated bacteria and decreased levels of proinflammatory chemokines (CXCL8 and CCL20) were observed. GRFT was not detected in plasma. GRFT and GRFT/CG in CVLs dose-dependently inhibited HIV and HPV, respectively, in vitro. The data suggest GRFT/CG is a promising on-demand multipurpose prevention product that warrants further investigation.
Project description:High-risk human papillomavirus (hr-HPV) has been implicated in a subset of patients with esophageal adenocarcinoma (EAC). We therefore hypothesized that HPV associated EAC may have distinct genomic aberrations compared with viral negative esophageal cancer as shown in Head and Neck cancer and cervical cancer. Whole exome sequencing (WES) was performed to explore the mutational landscape and potential molecular signature of HPV positive versus HPV negative EAC, which includes four hr-HPV-positive and 8 HPV-negative treatment naive fresh-frozen EAC tissue specimens and matched normal tissues.
Project description:mRNA sequencing was performed on 10 oropharyngeal cancer cell lines (5 HPV-positive and 5 HPV-negative cell lines) for this project. Two cell lines (CU-OP-17 and CU-OP-20) were newly derived from HPV-negative and HPV-positive tonsil cancers, respectively (described in " Sensitivity of human papillomavirus-positive and -negative oropharyngeal cancer cell lines to ionizing irradiation" by Holzhauser et al. This study was performed with the goal to identify differences in gene expression between irradiated and non-irradiated cell line samples. Additionally, the aim was to identify possible changes in genes, involved in DNA repair or DNA damage response of the HPV-positive and HPV-negative cell lines. The data published showed an increase of HPV integration sites after irradiation. Additionally, all HPV-positive cell lines in this study showed expression of HPV encoded genes. However, no direct correlation of changes or expression of DNA repair genes was identified.
Project description:Genome wide DNA methylation profiling of HPV positive and HPV negative head and neck squamous cell cancer (HNSCC) samples. The Illumina Infinium 450k Human DNA methylation Beadchip v1.1 was used to obtain DNA methylation profiles across approximately 485577 CpGs in 4 HPV positive and 4 HPV negative HNSCC tumors
Project description:Clinical treatment protocols for infertility with in vitro fertilization-embryo transfer (IVF-ET) provide a unique opportunity to assess the human vaginal microbiome in defined hormonal milieu. Herein, we have investigated the association of circulating ovarian-derived estradiol (E2) and progesterone (P4) concentrations to the vaginal microbiome. Thirty IVF-ET patients were enrolled in this study, after informed consent. Blood was drawn at four time points during the IVF-ET procedure. In addition, if a pregnancy resulted, blood was drawn at 4-to-6 weeks of gestation. The serum concentrations of E2 and P4 were measured. Vaginal swabs were obtained in different hormonal milieu. Two independent genome-based technologies (and the second assayed in two different ways) were employed to identify the vaginal microbes. The vaginal microbiome underwent a transition with a decrease in E2 (and/or a decrease in P4). Novel bacteria were found in the vagina of 33% of the women undergoing IVF-ET. Our approach has enabled the discovery of novel, previously unidentified bacterial species in the human vagina in different hormonal milieu. While the relationship of hormone concentration and vaginal microbes was found to be complex, the data support a shift in the microbiome of the human vagina during IVF-ET therapy using standard protocols. The data also set the foundation for further studies examining correlations between IVF-ET outcome and the vaginal microbiome within a larger study population.
Project description:ChIP-Seq for H3K27 trimethylation was performed for two HPV-positive and two HPV-negative squamous cell carcinoma cell lines. The data served two purposes. First, the data were used as an example implementation of our novel ChIP-Seq Peak Prioritization pipeline, PePr. We have developed the PePr pipeline, a ChIP-Seq Peak Prioritization pipeline that accounts for the variation among replicates and peak location relative to a gene. We show, using a transcription factor dataset (which exhibited small variation among samples), that PePr performs favorably compared to commonly used peak callers and that it achieves balanced sensitivity and specificity. We also show, using histone modification data (which exhibited larger variation among samples), that PePr can improve the detection of differential H3K27me3 regions compared with a common current approach. Using data from ChIP-Seq and gene expression experiments performed in parallel on the same samples, we show that the incorporation of functional annotations can improve the prioritization of functional sites. Secondly, the data were used to assess real differences in the genome-wide H3K27me3 profiles between HPV-positive and HPV-negative carcinoma cell lines. Careful analysis and integration of the data with DNA methylation and gene expression data performed on the same cell lines demonstrated striking differences exist. ChIP-Seq for H3K27 trimethylation was performed for two HPV-positive and two HPV-negative squamous cell carcinoma (SCC) cell lines. Input DNA was also sequenced for each sample to serve as a control. The goal was to determine overall differences in H3K27me3 patterns observed between the HPV-positive and HPV-negative SCC cell lines.
Project description:Human cancer cell lines are the most frequently used preclinical models in the study of cancer biology and the development of therapeutics. Although anatomically diverse, human papillomavirus (HPV)-driven cancers have a common etiology and similar mutations that overlap with but are distinct from those found in HPV-negative cancers. Building on prior studies that have characterized subsets of head and neck squamous cell carcinoma (HNSCC) and cervical squamous cell carcinoma (CESC) cell lines separately, we performed genomic, viral gene expression, and viral integration analyses on 74 cell lines that include all readily-available HPV-positive (9 HNSCC, 8 CESC) and CESC (8 HPV-positive, 2 HPV-negative) cell lines and 55 HPV-negative HNSCC cell lines. We used over 700 human tumors for comparison. Mutation patterns in the cell lines were similar to those of human tumors. We confirmed HPV viral protein and mRNA expression in the HPV-positive cell lines. We found HPV types in three CESC cell lines that are distinct from those previously reported. We found that cell lines and tumors had similar patterns of viral gene expression; there were few sites of recurrent HPV integration. As seen in tumors, HPV integration did appear to alter host gene expression in cell lines. The HPV-positive cell lines had higher levels of p16 and lower levels of Rb protein expression than did the HPV-negative lines. Although the number of HPV-positive cell lines is limited, our results suggest that these cell lines represent suitable models for studying HNSCC and CESC, both of which are common and lethal.