Project description:Uterine leiomyomas are the most common benign tumor in humans causing significant morbidity with vaginal bleeding, pelvic pressure and pain. Histologically, leiomyomas show a large degree of extracellular matrix disorganization. I am working with a colleague who recently found Notch pathway gene expression were clearly altered in fibroids (“Differential expression of the Notch signal transduction pathway: ligands, receptors and Numb in uterine leiomyomas vs. myometrium,” G. Christman, H. Tang, I. Ahmad, J. Stribley, Fertility and Sterility, Volume 88, Supp 1, S72, September 2007). Glycosaminoglycan expression was found to be over-expressed in uterine leiomyomas compared to myometrial samples (Fertility and Sterility, Vol 88 Supp 1, S106, September, 2007), but glycosyltransferase and glycosidase expression has not been reported. We have purified RNA samples from paired uterine leiomyoma and normal myometrium from a previous clinical study. Dr. Domino's laboratory hypothesis is that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth. Notch ligands are fucosylated glycans. The bulk of a fibroid is the extracellular matrix yet little has been studied on leiomyocyte expression of enzymes that model glycans in the extracellular matrix.
Project description:Gut microbial profiling of uterine fibroids (UFs) patients comparing control subjects. The gut microbiota was examined by 16S rRNA quantitative arrays and bioinformatics analysis. The goal was to reveal alterations in the gut microbiome of uterine fibroids patients.
Project description:Uterine leiomyomas are the most common benign tumor in humans causing significant morbidity with vaginal bleeding, pelvic pressure and pain. Histologically, leiomyomas show a large degree of extracellular matrix disorganization. I am working with a colleague who recently found Notch pathway gene expression were clearly altered in fibroids (“Differential expression of the Notch signal transduction pathway: ligands, receptors and Numb in uterine leiomyomas vs. myometrium,” G. Christman, H. Tang, I. Ahmad, J. Stribley, Fertility and Sterility, Volume 88, Supp 1, S72, September 2007). Glycosaminoglycan expression was found to be over-expressed in uterine leiomyomas compared to myometrial samples (Fertility and Sterility, Vol 88 Supp 1, S106, September, 2007), but glycosyltransferase and glycosidase expression has not been reported. We have purified RNA samples from paired uterine leiomyoma and normal myometrium from a previous clinical study. Dr. Domino's laboratory hypothesis is that Notch pathway activation inhibits apoptosis in uterine leiomyomas leading to fibroid growth. Notch ligands are fucosylated glycans. The bulk of a fibroid is the extracellular matrix yet little has been studied on leiomyocyte expression of enzymes that model glycans in the extracellular matrix. RNA preparations of paired samples of excess human tissues from hysterectomies, with two different groups normal myometrium, and leiomyoma tumors were sent to Microarray Core (E). The RNA was amplified, labeled, and hybridized to GLYCO_v3 microarrays.
Project description:Our study represents a new strategy for identifying drivers and risk factors of uterine fibroids (F) by identifying genes and pathways differentially regulated in myometrial stem cells (SCs) isolated from myometrium without fibroids (MyoN) and from myometrium adjacent to uterine fibroids (MyoF) using RNA-seq approach. Moreover, we will perform the comparison analysis of the transcriptome between MyoF SCs and fibroid SCs to identify differentially expressed genes.
Project description:Normal myometrium and uterine fibroids (partially paired from the same donor) were profiled. FISH analysis was used to analyze the karyotype of the uterine fibroid samples. This study provides further insights in the development of uterine fibroids. Additional uterine fibroid samples from the same sample collection and cohort can be found at ArrayExpress under E-MTAB-340.
Project description:Uterine fibroids are benign myometrial smooth muscle tumors of unknown etiology that when symptomatic are the most common indication for hysterectomy in the USA. We conducted an integrated analysis of fibroids and adjacent normal myometria by whole exome sequencing, DNA methylation (Human Methylation EPIC) array, and RNA-sequencing. Unsupervised clustering by DNA methylation segregated normal myometria and fibroids, and further separated the fibroids into subtypes marked by MED12 mutation, HMGA2 activation (HMGA2hi) and HMGA1 activation (HMGA1hi). Upregulation of HMGA2 expression in HMGA2hi fibroids did not always appear to be dependent on translocation, as has been historically described, and was associated with hypomethylation in the HMGA2 gene body. Furthermore, we found that expression of HOXA13 was highly upregulated in fibroids and that overexpression of HOXA13 in a myometrial cell line induced expression of genes classically associated with uterine fibroids. Transcriptome analyses of the most differentially expressed genes between cervix and myometrium also showed that uterine fibroids and normal cervix clustered together and apart from normal myometria. Together, our integrated analysis shows a role for epigenetic modification in fibroid biology and strongly suggests that homeotic transformation of myometrium cells to a more cervical phenotype is important for the etiology of the disease.
Project description:Uterine fibroids (leiomyomas) affect Black women disproportionately in terms of prevalence, incidence, and severity of symptoms. The causes of this racial disparity are essentially unknown. We hypothesized that myometria of Black women are more susceptible to developing fibroids and examined the transcriptomic and DNA methylation profiles of myometria and fibroids from Black and White women for comparison. Myometrial samples cluster by race in both their transcriptome and DNA methylation profiles, whereas fibroid samples only cluster by race in the latter. More differentially expressed genes (DEGs) were detected in the Black and White myometrial comparison than in the fibroid comparison. Leiomyoma gene set expression analysis showed four different clusters of DEGs, including a cluster with highest expression in Black myometrial samples and elevated in all fibroids. One of the DEGs in this group, VWF, was significantly hypomethylated at two CpG probes near a putative enhancer site in Black myometrial and in all fibroid samples compared with White myometrial samples, suggesting that VWF expression is responsive to DNA hypomethylation, a known stress response. These results suggest that the molecular basis for the disparity in fibroid disease between Black and White women could be found in the myometria before fibroid development and not in the fibroids themselves.
Project description:12q14~15 chromosomal rearrangements, specifically affecting the HMGA2 gene locus, are frequently observed in human uterine fibroids. Those fibroids are observed to show fast growth to a larger size compared to fibroids of normal karyotype. Since the HMGA2 gene is overexpressed, this study provides further insights in the development of uterine fibroids.