Aminobisphosphonates reactivate the latent reservoir in people living with HIV-1.

Antiretroviral therapy (ART) is not curative due to the existence of cellular reservoirs of latent HIV-1 that persist during therapy. Current research efforts to cure HIV-1 infection include "shock and kill" strategies to disrupt latency using small molecules or latency-reversing agents (LRAs) to induce expression of HIV-1 enabling cytotoxic immune cells to eliminate infected cells. The modest success of current LRAs urges the field to identify novel drugs with increased clinical efficacy.

Pre-treatment differential correlation of gene expression and response to topical steroids in eosinophilic esophagitis.

Few predictors of response to topical corticosteroid (tCS) treatment have been identified in eosinophilic esophagitis (EoE). We aimed to determine whether baseline gene expression predicts histologic response to tCS treatment for EoE. We analyzed prospectively collected samples from incident EoE cases who were treated with tCS for 8 weeks in a development cohort (prospective study) or in an independent validation cohort (clinical trial).

Tumor Cell Extrinsic Synaptogyrin 3 Expression as a Diagnostic and Prognostic Biomarker in Head and Neck Cancer.

Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal head and neck squamous cell carcinoma (HNSC) patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(-) squamous carcinomas. Candidate genes were tested in clinical specimens using both quantitative RT-PCR and IHC and validated by IHC using the Carolina Head and Neck Cancer Study (CHANCE) tissue microarray of HNSC cases.

Stretching muscle cells induces transcriptional and splicing transitions and changes in SR proteins.

Alternative splicing is an RNA processing mechanism involved in skeletal muscle development and pathology. Muscular diseases exhibit splicing alterations and changes in mechanobiology leading us to investigate the interconnection between mechanical forces and RNA processing. We performed deep RNA-sequencing after stretching muscle cells.

Genetic architecture modulates diet-induced hepatic mRNA and miRNA expression profiles in Diversity Outbred mice.

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression.

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors.

Transcriptional silencing of HIV in CD4 T cells generates a reservoir of latently infected cells that can reseed infection after interruption of therapy. As such, these cells represent the principal barrier to curing HIV infection, but little is known about their characteristics. To further our understanding of the molecular mechanisms of latency, we characterized a primary cell model of HIV latency in which infected cells adopt heterogeneous transcriptional fates.

Genetic Architecture Modulates Diet-Induced Hepatic mRNA and miRNA Expression Profiles in Diversity Outbred Mice.

Genetic approaches in model organisms have consistently demonstrated that molecular traits such as gene expression are under genetic regulation, similar to clinical traits. The resulting expression quantitative trait loci (eQTL) have revolutionized our understanding of genetic regulation and identified numerous candidate genes for clinically relevant traits. More recently, these analyses have been extended to other molecular traits such as protein abundance, metabolite levels, and miRNA expression.

FGFR4 regulates tumor subtype differentiation in luminal breast cancer and metastatic disease.

Mechanisms driving tumor progression from less aggressive subtypes to more aggressive states represent key targets for therapy. We identified a subset of luminal A primary breast tumors that give rise to HER2-enriched (HER2E) subtype metastases, but remain clinically HER2 negative (cHER2-). By testing the unique genetic and transcriptomic features of these cases, we developed the hypothesis that FGFR4 likely participates in this subtype switching.

microRNA-146a-5p association with the cardiometabolic disease risk factor TMAO.

Trimethylamine-N-oxide (TMAO), a microbial choline metabolism byproduct that is processed in the liver and excreted into circulation, is associated with increased atherosclerotic lesion formation and cardiovascular disease risk. Genetic regulators of TMAO levels are largely unknown. In the present study, we used 288 mice from a genetically heterogeneous mouse population [Diversity Outbred (DO)] to determine hepatic microRNA associations with TMAO in the context of an atherogenic diet.

Adropin: An endocrine link between the biological clock and cholesterol homeostasis.

Objective: Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods: Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Systems genetics identifies a co-regulated module of liver microRNAs associated with plasma LDL cholesterol in murine diet-induced dyslipidemia.

Chronically altered levels of circulating lipids, termed dyslipidemia, is a significant risk factor for a number of metabolic and cardiovascular morbidities. MicroRNAs (miRNAs) have emerged as important regulators of lipid balance, have been implicated in dyslipidemia, and have been proposed as candidate therapeutic targets in lipid-related disorders including atherosclerosis. A major limitation of most murine studies of miRNAs in lipid metabolic disorders is that they have been performed in just one (or very few) inbred strains, such as C57BL/6.