Project description:A major challenge to the study and treatment of neurogenetic syndromes is the difficulty in gaining access to live neurons from individuals with these disorders. Although other sources of stem cells are currently available for differentiation into neurons, these can involve invasive procedures and be difficult or expensive to generate limiting their use on a broad scale, especially for rare syndromes which may not be well represented in the local population. Dental pulp stem cells (DPSC) are neural crest derived multipotent stem cells that reside deep the pulp of shed (baby) teeth and have the potential for broad use in the study of neurogenetic disease. In order to investigate the characteristics of DPSC which make them a valuable resource for the study of neurogenetic syndromes we performed a set of viability, senescence and immortalization studies on control DPSC and DPSC derived neurons. We investigated the basic transport conditions and determined the maximum passage number for primary DPSCs. We then immortalized control DPSC using human telomerase reverse trancriptase (hTERT) and evaluated both neuronal differentiation potential and gene expression changes using RNAseq. Here we show that immortalized DPSC share morphological and electrophysiological properties with non-immortalized DPSC. We also show that differentiation of DPSC into neurons changes gene expression for 1305 transcripts, while immortalized neurons differ significantly in gene expression for 183 transcripts of which 94 also changed during differentiation. Taken together, these studies indicate that immortalized dental pulp derived neruons may be a new and powerful resource for the study of rare neurological disorders where patient samples are rare or difficult to obtain. RNA-seq Analysis of 3 neurotypical control DPSC, 3 DPSC derived neurons and 3 each immortalized versions of DPSC and DPSC neurons (~3 weeks post maturation)
Project description:131 patient-derived xenograft models were generated for non-small cell lung carcinoma and were profiled by analysis of gene copy number variation, whole exome sequence, methylome, transcriptome, proteome, and phospho(Tyr)-proteome. Proteome profiling resolved the known major histology subtypes and revealed 3 proteome subtypes (proteotypes) among adenocarcinoma and 2 in squamous cell carcinoma that were associated with distinct protein-phosphotyrosine signatures and patient survival. Proteomes of human tumor were discernible from murine stroma. Stromal proteomes were similar between histological subtypes, but two adenocarcinoma proteotypes had distinct stromal proteomes. Tumor and stromal proteotypes comprise signatures of targetable biological pathways suggesting that patient stratification by proteome profiling may be an actionable approach to precisely diagnose and treat cancer.
Project description:Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in chronic obstructive pulmonary disease patients with emphysema. The antimicrobial effects of AZM on the lung microbiome are not known and may contribute to its beneficial effects. Methods. Twenty smokers with emphysema were randomized to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements included: rDNA gene quantity and sequence. Results. Compared with placebo, AZM did not alter bacterial burden but reduced α-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Conclusions. AZM treatment the lung microbiome Randomized trial comparing azithromycin (AZM) treatment with placebo for eight weeks. Bronchoalveolar lavage (BAL) samples were obtained before and after treatment to explore the effects of AZM on microbiome, in the lower airways. 16S rRNA was quantified and sequenced (MiSeq) The amplicons from total 39 samples are barcoded and the barcode is provided in the metadata_complete.txt file.
Project description:Huntington's disease is caused by an expanded CAG repeat in the huntingtin gene, yeilding a Huntingtin protein with an expanded polyglutamine tract. Patient-derived induced pluripotent stem cells (iPSCs) can help understand disease; however, defining pathological biomarkers in challanging. Here we used LC-MS/MS to determine differences in mitochondrial proteome between iPSC-derived neurons from healthy donors and Huntington's disease patients.