A5085074001- RNA Research and Splicing
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Radiomics and Machine Learning in Medical Imaging
- Gene expression and cancer classification
- Peroxisome Proliferator-Activated Receptors
- RNA and protein synthesis mechanisms
- AI in cancer detection
- Genomics and Chromatin Dynamics
- Glycosylation and Glycoproteins Research
- Genetic Mapping and Diversity in Plants and Animals
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Mesenchymal stem cell research
- Lung Cancer Treatments and Mutations
- Bioinformatics and Genomic Networks
- Adipose Tissue and Metabolism
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Telomeres, Telomerase, and Senescence
- Cardiac Ischemia and Reperfusion
- S100 Proteins and Annexins
- Genomic variations and chromosomal abnormalities
- Neuroblastoma Research and Treatments
Indiana University – Purdue University Indianapolis
2012-2024
Indiana University School of Medicine
2012-2024
Indiana University
2012-2024
University School
2021-2024
Indiana Clinical and Translational Sciences Institute
2020
Yale University
2006-2010
Mayo Clinic
1996-2010
Yale Cancer Center
2010
Mayo Clinic in Arizona
1996-2002
Children's Hospital of Philadelphia
1998
Glyphosate (GLY) is the most heavily used herbicide worldwide but extent of exposure in human pregnancy remains unknown. Its residues are found environment, major crops, and food items that humans, including pregnant women, consume daily. Since GLY may also increase fetal risk, we designed a birth-cohort study to determine frequency, potential pathways, associations with growth indicators length.
Abstract Background: Despite the widespread use of immunohistochemistry (IHC), there are no standardization guidelines that control for antibody probe variability. Here we describe effect variable reagents in assessment cancer-related biomarkers by IHC. Methods: Estrogen receptor (ER), epidermal growth factor (EGFR) 1, and human 3 (HER3) were evaluated quantitative immunofluorescence. Correlations between ER clones 1D5, SP1, F10, ER60c, EGFR monoclonal 31G7, 2-18C9, H11, 15F8, polyclonal...
Single nucleotide variants (SNVs) in intronic regions have yet to be systematically investigated for their disease-causing potential. Using known pathogenic and neutral SNVs (iSNVs) as training data, we develop the RegSNPs-intron algorithm based on a random forest classifier that integrates RNA splicing, protein structure, evolutionary conservation features. showed excellent performance evaluating impacts of iSNVs. high-throughput functional reporter assay called ASSET-seq (ASsay Splicing...
Abstract Background Prenatal glyphosate (GLY) exposure is associated with adverse reproductive outcomes in animal studies. Little known about the effects of GLY during pregnancy human population. This study aims to establish baseline urine levels a high-risk and racially diverse cohort assess relationship between prenatal fetal development birth outcomes. Methods Random first trimester specimens were collected from high risk pregnant women 2013 2016 as part Indiana Pregnancy Environmental...
The epidermal growth factor receptor (EGFR) is encoded by the c- erbB 1 proto-oncogene and plays an important role in control of cell differentiation. To study potential regulatory soluble EGF receptors, we have isolated cDNA clones encoding a truncated, secreted form human EGFR. 5′ sequence this identical to EGFR transcript full-length through exon 10. unique 3′ encodes two additional amino acid residues before encountering in-frame stop codon, poly(A) addition site + tail. Sequence...
Abstract Genome-wide association studies (GWAS) of complex traits, such as alcohol use disorders (AUD), usually identify variants in non-coding regions and cannot by themselves distinguish whether the associated are functional or linkage disequilibrium with variants. Transcriptome can genes whose expression differs between alcoholics controls. To test which AUD may cause differences, we integrated data from deep RNA-seq GWAS four postmortem brain 30 subjects controls to analyze...
Abstract Neoantigen peptides arising from genetic alterations may serve as targets for personalized cancer vaccines and positive predictors of response to immune checkpoint therapy. Mutations in genes regulating RNA splicing are common hematological malignancies leading dysregulated intron retention (IR). In this study, we investigated IR a potential source tumor neoantigens multiple myeloma (MM) patients the relationship IR-induced (IR-neoAg) with clinical outcomes. MM-specific events were...
Cumulative information available about the organization of amplified chromosomal regions in human tumors suggests that amplification repeat units, or amplicons, can be a simple complex nature. For former, generally retain their native configuration and involve single target sequence. DNAs usually undergo substantial reorganization relative to normal from which they evolve, subject may contain multiple sequences. Previous efforts characterize 7p11.2 epidermal growth factor receptor (EGFR)...
Although genome-wide association studies (GWAS) have identified loci associated with alcohol consumption and use disorder (AUD), they do not identify which variants are functional. To approach this, we evaluated the impact of in 3' untranslated regions (3'-UTRs) genes substance neurological disorders using a massively parallel reporter assay (MPRA) neuroblastoma microglia cells. Functionally impactful explained higher proportion heritability traits than non-functional variants. We whose...
High tumor mutation burden (TMB) in many cancer types is associated with the production of tumor-specific neoantigens, a favorable outcome and response to immune checkpoint blockade (ICB) therapy. Besides mutation-derived aberrant intron retention also produces neopeptides that could trigger an response. The relationship between intron-retention-derived neoantigens (IR-neoAg) clinical outcomes pancreatic remains uncertain. Here, we quantify IR-neoAg evaluate whether load might serve as...
Abstract Alcohol use disorder (AUD) is a complex genetic characterized by problems arising from excessive alcohol consumption. Identifying functional variations that contribute to risk for AUD major goal. Alternative splicing of RNA mediates the flow information DNA gene expression and expands proteome diversity. We asked whether alternative could be factor AUD. Herein, we used Mendelian randomization (MR)-based approach identify skipped exons (the predominant event in brain) risk. Genotypes...
The MYCN proto-oncogene is amplified in 25% of neuroblastomas, and amplification strongly correlated with advanced disease stage rapid tumor progression. We have generated a high-resolution restriction map nearly 500 kb spanning the locus by subcloning yeast artificial chromosomes into cosmids. Cosmids plus additional probes were hybridized to DNA from 33 we determined that amplicons range 350 over 1 Mb. Deletions rearrangements amplicon occurred less frequently primary tumors than cell...
Bone marrow-derived mesenchymal stem cells (MSCs) improve cardiac function after ischemia/reperfusion injury, in part, due to the release of cytoprotective paracrine factors. Toll-like receptor 4 (TLR4) is expressed MSCs and regulates expression factors, cytokines, chemokines. Lipopolysaccharide (LPS) stimulation TLR4 activates two distinct signaling pathways that are either MyD88 dependent or independent/TIR-domain-containing adapter-inducing interferon-β (TRIF) dependent. While it was...
Single-cell RNA sequencing reveals gene expression differences between individual cells and also identifies different cell populations that are present in the bulk starting material. To obtain an accurate assessment of patient samples, single-cell suspensions need to be generated as soon possible once tissue or sample has been collected. However, this requirement poses logistical challenges for experimental designs involving multiple samples from same subject since these would ideally...
Mesenchymal stem cells (MSC) are multipotent that can differentiate into multiple cell types, including osteoblasts, chondrocytes, and adipocytes. Osteoblast differentiation is reduced during osteoporosis development, resulting in bone formation. Further, MSC isolated from different donors possess distinct osteogenic capacity. In this study, we used single-cell multiomic analysis to profile the transcriptome epigenome of four healthy donors. Data were obtained ~1300 1600 for each donor....
Abstract Alcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq ATAC-seq on samples from 143 human postmortem brains, 74 with AUD, we identified 17 distinct cell types. We found that a significant portion of alcohol-induced in gene expression occurred through altered chromatin accessibility. Notably, novel accessibility differences medium...
Humans show sex differences related to alcohol use disorders. Animal model research has the potential provide important insight into how affect consumption, particularly because female animals frequently drink more than males. In previous work, inbred strains of selectively-bred alcohol-preferring (P) and nonpreferring (NP) rat lines revealed a highly significant quantitative trait locus (QTL) on chromosome 4, with logarithm odds score 9.2 for consumption. Recently, interval-specific...
MYCN amplification in neuroblastomas is strongly associated with advanced stages of disease and a poor prognosis. We have recently defined 130 kb core region the amplicon that consistently amplified neuroblastomas. However, it has been argued other expressed sequences were coamplified and, as result, might contribute to aggressive phenotype MYCN-amplified Therefore, we screened cosmids representing domain surrounding DNA by using differential hybridization approach detect amplified, highly...
The ErbB tyrosine kinase receptor family plays an important role in normal cellular growth and differentiation. In addition, members are commonly amplified overexpressed various human neoplasms tumor-derived cell lines, where it is believed that increased signalling as a result of overexpression may play oncogenesis. Consequently, being investigated rigorously potential biomarkers cancer therapeutic targets malignant tissues. Numerous studies now demonstrate the existence "soluble" (sErbB)...
Abstract Background Existing studies have demonstrated that the integrative analysis of histopathological images and genomic data can be used to better understand onset progression many diseases, as well identify new diagnostic prognostic biomarkers. However, since development pathological phenotypes are influenced by a variety complex biological processes, complete understanding underlying gene regulatory mechanisms for cell tissue morphology is still challenge. In this study, we explored...