Longitudinal analysis of monocyte gene expressions patterns before and after cessation of HAART: understanding the impact of HIV viremia on the monocyte tranascritome. We used microarrays to detail the global program of gene expression underlying defects in monocytes from HIV infected patients during viremia..
Diminished production of monocyte proinflammatory cytokines during human immunodeficiency virus viremia is mediated by type I interferons.
No sample metadata fields
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Sex, Age, Specimen part, Disease
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Sex, Age, Specimen part, Disease
View SamplesHodgkin lymphoma is derived from germinal center / post-germinal center B cells.
Gene expression profiling of microdissected Hodgkin Reed-Sternberg cells correlates with treatment outcome in classical Hodgkin lymphoma.
Specimen part
View SamplesWe identified recurrent NOTCH1 mutations in 12% of MCLs. 2 out of 10 tested MCL cell lines (Rec-1 and SP-49) were sensitive to inhibition of the NOTCH pathway by gamma-secretase inhibition.
Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma.
Specimen part, Cell line
View SamplesWe sought to determine differences in transcript expression between a cohort of HIV-infected individuals that either developed broadly neutralizing antibodies (bnAb) or did not develop them (control). With the ultimate goal to identify transcripts that are associated with the development of bnAbs that would identify novel pathways that could be targeted in future vaccine strategies to increase the frequency of individuals that develop bnAbs against HIV. Using this approach we identified that Rab11 recycling endosomes, particularly in dysfunctional natural killer cells are associated with the development of HIV-1 bnAbs. Overall design: RNA extracted from peripheral blood mononuclear cells of 95 subjects was subject to RNA-seq for transcriptome analysis comparing individuals that developed HIV-1 broadly neutralizing antibodies to those that did not develop them (control).
RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses.
Specimen part, Disease stage, Subject
View SamplesCancer treatments often require combinations of molecularly targeted agents to be effective. mTORi (rapamycin) and HDACi (MS-275/entinostat) inhibitors have been shown to be effective in limiting tumor growth, and here we define part of the cooperative action of this drug combination. More than 60 human cancer cell lines responded synergistically (CI<1) when treated with this drug combination compared to single agents. In addition, a breast cancer patient-derived xenograft, and a BCL-XL plasmacytoma mouse model both showed enhanced responses to the combination compared to single agents. Mice, bearing plasma cell tumors lived an average of 70 days longer on combination treatment compared to single agents. A set of 37 genes cooperatively affected (34 down-regulated; 3 up-regulated) by the combination responded pharmacodynamically in human myeloma cell lines, xenografts, and a P493 model, and were both enriched in tumors, and correlated with prognostic markers in myeloma patient datasets. Genes down-regulated by the combination were overexpressed in several untreated cancers (breast, lung, colon, sarcoma, head and neck, myeloma) compared to normal tissues. The MYC/E2F axis, identified by upstream regulator analyses and validated by immunoblots, was significantly inhibited by the drug combination in several myeloma cell lines. Furthermore, 88% of the 34 genes downregulated have MYC binding sites in their promoters, and the drug combination cooperatively reduced MYC half-life by 55% and increased degradation. Thus, integrative approaches to understand drug synergy identified a clinically actionable strategy to inhibit MYC/E2F activity and tumor cell growth in vivo.
Cooperative Targets of Combined mTOR/HDAC Inhibition Promote MYC Degradation.
No sample metadata fields
View SamplesThe majority of transplanted organs are recovered from deceased donors after brain death (BD). BD has been hypothesized to compromise organ quality in part from the activation of systemic inflammation. The objective of this study was to characterize the immune response induced by BD in a well controlled non-human primate (NHP) model. Assessment of physiologic parameters (blood pressure, heart rate, urinary output, catecholamines, and cerebral angiograms) was used to confirm BD. After 6h of BD, we monitored changes in the peripheral blood by flow cytometry, liver gene expression by microarray and liver protein expression by Western blotting and immunohistochemistry (IHC). BD was indicated by a rapid increase in blood pressure followed by hemodynamic instability, hypotension, diabetes insipidus and the absence of cerebral blood flow and brain stem reflexes. Within the peripheral blood IL-6 levels and neutrophils increased and myeloid dendritic cells decreased in BD NHP when compared to living donor controls. Genes related to innate inflammatory response and apoptosis were significantly upregulated in BD NHP. BD livers showed increased expression of suppressor of cytokine signaling 3 (SOCS3) protein and the danger associated molecular pattern protein S100A9. Increased expression of intracellular cellular adhesion molecule 1 (ICAM-1) and major histocompatibility complex (MHC) II, neutrophil accumulation, and products of oxidative stress (carboxy methyl lysine (CML) and hydroxynonenal (HNE)) were detected by IHC in livers. Conclusion: These data indicate that BD leads to the rapid activation of an inflammatory response within the liver involving components of the innate immune response at the gene and protein levels. The activation of these inflammatory pathways may provide one explanation for the reduced post-transplant function of organs from brain dead donors.
Early activation of the inflammatory response in the liver of brain-dead non-human primates.
Sex, Age, Specimen part
View SamplesNon-neuronal cell types such as astrocytes can contribute to Parkinson's disease (PD) pathology. The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is one of the most common known causes of familial PD. To characterize its effect on astrocytes, we developed a protocol to produce midbrain-patterned astrocytes from human induced pluripotent stem cells (iPSCs) derived from PD LRRK2 G2019S patients and healthy controls. In order to understand the effect of this mutation on astrocyte function, we compared the gene expression profiles of iPSC-derived midbrain-patterned astrocytes from PD patients with those from healthy controls. Overall design: Bulk RNA-Seq profiles of human iPSC-derived midbrain-patterned astrocytes from 7 donors, including 4 patients with Parkinson's disease who carry the LRRK2 G2019S mutation, and 3 healthy control individuals
RNA sequencing reveals MMP2 and TGFB1 downregulation in LRRK2 G2019S Parkinson's iPSC-derived astrocytes.
Sex, Specimen part, Cell line, Subject
View SamplesGene expression data for shRNA PTPN1 knockdown vs. Non-silencing in the classical Hodgkin lymphoma-derived cell line KM-H2
Recurrent somatic mutations of PTPN1 in primary mediastinal B cell lymphoma and Hodgkin lymphoma.
Specimen part, Cell line
View Samples