- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Glioma Diagnosis and Treatment
- MicroRNA in disease regulation
- Wnt/β-catenin signaling in development and cancer
- Genomic variations and chromosomal abnormalities
- Nuclear Receptors and Signaling
- Genomics and Chromatin Dynamics
- Gene expression and cancer classification
- T-cell and B-cell Immunology
- Carbohydrate Chemistry and Synthesis
- Chromatin Remodeling and Cancer
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Epigenetics and DNA Methylation
- Immunotherapy and Immune Responses
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Systemic Lupus Erythematosus Research
- Immune responses and vaccinations
- Bioinformatics and Genomic Networks
- Cancer-related Molecular Pathways
- Influenza Virus Research Studies
National Institutes of Health
2013-2025
National Cancer Institute
2006-2024
Cancer Institute (WIA)
2006-2023
Georgetown University
2023
Clinical Research Consortium
2016
Sidra Medical and Research Center
2016
National Institute of Neurological Disorders and Stroke
2006-2014
National Heart Lung and Blood Institute
2013
Center for Cancer Research
2009
RIKEN Center for Brain Science
2005
Finding better therapies for the treatment of brain tumors is hampered by lack consistently obtained molecular data in a large sample set and ability to integrate biomedical from disparate sources enabling translation bench bedside. Hence, critical factor advancement research clinical ease with which can be integrated, redistributed, analyzed both within across functional domains. Novel informatics infrastructure tools are essential developing individualized patient based on specific genomic...
SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity specificity. In this work, we present a comprehensive meta-analysis performance based on multiple serum plasma runs using the current 1.3 k assay, as well previous 1.1 version. We discuss normalization procedures examine different strategies to minimize intra- interplate nuisance effects. implement calibrator samples...
Abstract Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled trial SLE subjects (ClinicalTrials.gov NCT02535689). study, 30 are randomized...
Genetic aberrations, such as gene amplification, deletions, and loss of heterozygosity, are hallmarks cancer thought to be major contributors the neoplastic process. Established cell lines have been primary in vitro vivo models for more than 2 decades; however, few extensively characterized at genomic level. Here, we present a high-resolution genome-wide chromosomal alteration expression analyses five most commonly used glioma compare findings with those observed 83 human gliomas. Although...
Glycogen synthase kinase 3 (GSK3), a serine/threonine kinase, is involved in diverse cellular processes ranging from nutrient and energy homeostasis to proliferation apoptosis. Its role glioblastoma multiforme has yet be elucidated. We identified GSK3 as regulator of cell survival using microarray analysis small-molecule genetic inhibitors activity. Various molecular approaches were then used dissect out the mechanisms responsible for inhibition-induced cytotoxicity. show that multiple small...
Abstract Gliomas are the most common type of primary brain tumors in adults and a significant cause cancer-related mortality. Defining glioma subtypes based on objective genetic molecular signatures may allow for more rational, patient-specific approach to therapy future. Classifications gene expression data have been attempted past with varying success only some concordance between studies, possibly due inherent bias that can be introduced through use analytic methodologies make priori...
Abstract Corticosteroids have been used for decades to modulate inflammation therapeutically, yet there is a paucity of data on their effects in humans. We examined the changes cellular and molecular immune system parameters, or “immunome”, healthy humans after systemic corticosteroid administration. multiplexed techniques query immunome 20 volunteers at baseline, intravenous hydrocortisone (HC) administered moderate (250 mg) low (50 doses, provide insight into how corticosteroids exert...
Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination an important mechanism of protection against infection. Despite the overall public health success vaccination, many fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional cell subset signatures with responses. However, existing relied on small cohorts not been validated in large...
Low-dose interleukin-2 (IL-2) expands regulatory T cells (Tregs) and natural killer (NK) after stem cell transplantation (SCT) may reduce graft-versus-host disease (GVHD). We hypothesized that ultra-low dose (ULD) IL-2 could serve as an immune-modulating agent for donors to prevent GVHD following SCT. However, the safety, level, immune signatures of ULD in immune-competent healthy subjects remain unknown. Here, we have characterized phenotype function Tregs NK well gene expression cytokine...
Abstract Primary brain tumors are the fourth leading cause of cancer mortality in adults under age 54 years and children United States. Therapy for most common type primary tumors, gliomas, remains suboptimal. The development new more effective treatments will likely require a better understanding biology these tumors. Here, we show that use high-density 100K single-nucleotide polymorphism arrays large number tumor samples allows much higher resolution survey glioma genome than has been...
The Notch pathway plays a key role in the development and is increasingly recognized for its importance cancer. We demonstrated previously overexpression of Notch-1 ligands gliomas showed that their knockdown inhibits glioma cell proliferation survival. To elucidate mechanisms downstream cells, we performed microarray profiling cells transfected with small interfering RNA. Notable among downregulated transcripts was epidermal growth factor receptor (EGFR), known to be overexpressed or...
Despite progress in the determination of miR interactions, their regulatory role cancer is only beginning to be unraveled. Utilizing gene expression data from 27 glioblastoma samples we found that mere knowledge physical interactions between specific mRNAs and miRs can used determine associated allowing us identify 626 involving 128 putatively modulate 246 mRNAs. Experimentally determining miRs, an over-representation over(under)-expressed with various predicted mRNA target sequences. Such...
Age is a powerful predictor of survival in glioblastoma multiforme (GBM) yet the biological basis for difference clinical outcome mostly unknown. Discovering genes and pathways that would explain age-specific could generate opportunities novel therapeutics GBM. Here we have integrated gene expression, exon microRNA copy number alteration, SNP, whole exome sequence, DNA methylation data sets cohort GBM patients The Cancer Genome Atlas (TCGA) project to discover signatures at transcriptional,...
Immune responses to inactivated vaccines against avian influenza are poor due in part lack of immune memory. Adjuvants significantly increased virus neutralizing titers. We performed comprehensive analyses polyclonal antibody following FDA-approved adjuvanted H5N1-A/Indonesia vaccine, administered presence or absence AS03. Using Whole Genome Fragment Phage Display Libraries, we observed that AS03 induced epitope diversity viral hemagglutinin (HA) and neuraminidase compared with unadjuvanted...
Abstract Huntington disease is caused by polyglutamine (polyQ) expansion in huntingtin. Selective and progressive neuronal loss observed the striatum cerebral cortex disease. We have addressed whether expanded polyQ aggregates appear regions of brain apart from there a correlation between aggregate formation dysregulated transcription. generated transgenic mouse lines expressing mutant truncated N‐terminal huntingtin (expanded polyQ) fused with enhanced green fluorescent protein (EGFP)...
Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains cell invasion. In this study, we used unique microarray profiling approach on human stem (GSC) xenograft model explore gene expression changes in situ Invading Glioma Cells (IGCs) compared...
Changes in adaptive immune cells after chemotherapy adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. This study was designed to determine functional capacity system patients with AML who completed and are potential candidates We used response seasonal influenza vaccination as a surrogate robustness 10 complete remission post-chemotherapy performed genetic, phenotypic, characterization cell subsets. Only 2 generated protective titers vaccination,...