NHLBI TOPMed – NHGRI: INSIGHTS Study: Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study
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PROVIDER: PRJNA1279277 | ENA |
REPOSITORIES: ENA
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Project description:NHLBI TOPMed – NHGRI: INSIGHTS Study: Insights into Microbiome and Environmental Contributions to Sickle Cell Disease and Leg Ulcers Study
| PRJNA1279276 | ENA
Project description:Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. Keywords: ChIP/chip NHGRI Menin ChIP-Chip
2006-07-24 | E-GEOD-5357 | biostudies-arrayexpress
Project description:NHGRI Large Scale Sequencing Program
| PRJNA158497 | ENA
Project description:NHGRI Mendelian Disorders Sequencing Centers
| PRJNA158501 | ENA
Project description:We performed RNAseq on ulcers and distant normal tissue from biopsy-wounded wild-type and Bmp4-overexpressing (Vil1-Cre;Rosa26-Bmp4) mice to investigate differences in gene expression between tissue states and genotypes. Biopsy wounding was performed by taking three biopsies from well-separated areas in the colon wall using forceps. Small tissue pieces were excised from the ulcers and distant normal colon tissue and collected for RNA sequencing.
2021-05-09 | E-MTAB-10238 | biostudies-arrayexpress
Project description:Chronic non-healing venous leg ulcers (VLUs) are a widespread debilitating disease with high morbidity and associated costs, as approximately $15 billion annually are spent on the care of VLUs. Despite their socioeconomic burden, there is a paucity of novel treatments targeted towards healing VLUs, which can be attributed to both lack of pathophysiologic insight into VLU development as well as lack of knowledge regarding biologic actions of VLU-targeted therapies. Currently, the bioengineered bilayered living cellular construct (BLCC) skin substitute is the only FDA-approved biologic treatment for healing VLUs. To elucidate the mechanisms through which the BLCC promotes healing of chronic VLUs, we conducted a clinical trial (NCT01327937) in which patients with non-healing VLUs were treated with either standard care (compression therapy) or with BLCC together with standard care. Tissue was collected from the VLU edge before and 1 week after treatment, and samples underwent comprehensive microarray, mRNA and protein analyses. Ulcers treated with BLCC skin substitute displayed three distinct patterns suggesting the mechanisms by which BLCC shifted a non-healing into a healing tissue response: it modulated inflammatory and growth factor signaling; it activated keratinocytes; and it attenuated Wnt/β-catenin signaling. In these ways, BLCC application orchestrated a shift of the chronic non-healing ulcer microenvironment into a distinctive healing milieu resembling that of an acute, healing wound. Our findings also provide first patient-derived in vivo evidence of specific biologic processes that can be targeted in the design of therapies to promote healing of chronic VLUs.
2016-09-01 | GSE84571 | GEO
Project description:Leg ulcers are estimated to occur in 1%-10% of North American patients with sickle cell disease (SCD). Their pathophysiology remains poorly defined, but as with other chronic wounds, it is hypothesised that the microbial milieu, or microbiome, contributes to their healing and clinical outcomes. This study utilises 16S ribosomal RNA (rRNA) gene sequencing to describe, for the first time, the microbiome of the SCD leg ulcer and its association with clinical factors. In a cross-sectional analysis of 42 ulcers, we recovered microbial profiles similar to other chronic wounds in the predominance of anaerobic bacteria and opportunistic pathogens including Staphylococcus, Corynebacterium, and Finegoldia. Ulcers separated into two clusters: one defined by predominance of Staphylococcus and smaller surface area, and the other displaying a greater diversity of taxa and larger surface area. We also find that the relative abundance of Porphyromonas is negatively associated with haemoglobin levels, a key clinical severity indicator for SCD, and that Finegoldia relative abundance is negatively associated with CD19+ B cell count. Finally, ratios of Corynebacterium:Lactobacillus and Staphylococcus:Lactobacillus are elevated in the intact skin of individuals with a history of SCD leg ulcers, while the ratio of Lactobacillus:Bacillus is elevated in that of individuals without a history of ulcers. Investigations of the skin microbiome in relation to SCD ulcer pathophysiology can inform clinical guidelines for this poorly understood chronic wound, as well as enhance broader understanding about the role of the skin microbiome in delayed wound healing.
| S-EPMC8410641 | biostudies-literature
Project description:NHGRI Clinical Sequencing Exploratory Research Program
| PRJNA158503 | ENA
Project description:Marjolin's ulcer is a a rare and aggressive cutaneous malignancy that can arise on previously injured skin, established scars, and chronic non-healing wounds. It is most often found in burn scars, but it can also occur in other types of wounds, including venous stasis ulcers, pressure sores, and vaccination sites. The most common histological type of Marjolin’s ulcers is squamous cell carcinoma, however basal cell carcinomas, malignant melanomas, and sarcomas have also been reported. All parts of the body could potentially be affected yet the lower extremities are the anatomic sites most commonly involved. While SCCs commonly have a metastasis rate of 0.5 to 3.0 percent, those arising from burn scars metastasize at a rate in excess of 30 percent. The 5-year survival after a diagnosis of Marjolin’s ulcer was found to be 50 percent. The transformation to a malignancy can occur either chronically, over a period of more than 35 years, or occasionally within a year of the original injury. The exact mechanism of this transformation is not fully understood, but it is thought to be related to chronic keratinocyte dysfunction during the healing process of severe burn wounds. Surgical excision is the main treatment for Marjolin's ulcer and provides the best chance of survival. In a previous study, we investigated the bulk transcriptional changes that lead to Marjolin's ulcer by comparing global gene expression changes between squamous cells present in a squamous cell carcinoma versus those present within Marjolin's ulcer (MU) (Sinha et. al. JBCR 2017). This imparted novel insights into mechanisms underlying divergent clinical features of these cutaneous cancers. The goal of our current study is to characterize a new case of Marjolin's ulcer in a patient under our care by analyzing the cell types, their frequencies, and their individual transcriptional responses within a burn scar versus within Marjolin's ulcer. To achieve this, we conducted single-cell RNA sequencing on two excised tissues: 1. a sample from the center of the tumor (tumor core), and 2. another sample from the margin of tumor-free scar tissue.
2024-07-21 | GSE234919 | GEO