A5038848441- Epigenetics and DNA Methylation
- Genomics and Chromatin Dynamics
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- 14-3-3 protein interactions
- Multiple Myeloma Research and Treatments
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Hemoglobinopathies and Related Disorders
- Cytokine Signaling Pathways and Interactions
- Axon Guidance and Neuronal Signaling
- Lung Cancer Treatments and Mutations
- interferon and immune responses
- Monoclonal and Polyclonal Antibodies Research
- Cell Image Analysis Techniques
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Immunotherapy and Immune Responses
- Transgenic Plants and Applications
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Cancer therapeutics and mechanisms
- Chromatin Remodeling and Cancer
- Retinoids in leukemia and cellular processes
AstraZeneca (United States)
2019
National Institutes of Health
2006-2011
National Institute of Diabetes and Digestive and Kidney Diseases
2009
University of Florida
2004
Although cancer is largely seen as a disease stemming from genetic mutations, evidence has implicated epigenetic regulation of gene expression driving force for tumorigenesis. Epigenetic by histone modification, specifically through polycomb group (PcG) proteins such EZH2 and BMI-1, major driver in stem cell biology found to be correlated with poor prognosis many tumor types. This suggests role PcG cells (CSCs). We hypothesized that modification EZH2, specifically, helps maintain the CSC...
The dynamic packaging of DNA into chromatin is a fundamental step in the control diverse nuclear processes. Whereas certain transcription factors and chromosomal components promote formation higher-order loops, co-regulator machinery mediating loop assembly disassembly unknown. Using mice bearing hypomorphic allele BRG1 remodeler, we demonstrate that Brg1 mutation abrogated cell type-specific between beta-globin locus region downstream beta major promoter, despite trans-acting factor...
Antibody-drug conjugates (ADC) utilizing noncleavable linker drugs have been approved for clinical use, and several are in development targeting solid hematologic malignancies including multiple myeloma. Currently, there no reliable biomarkers of activity these ADCs other than presence the targeted antigen. We observed that certain cell lines innately resistant to such ADCs, sought uncover underlying mechanism resistance.The expression 43 lysosomal membrane target genes was evaluated bearing...
The establishment of epigenetic marks, such as methylation on histone tails, is mechanistically linked to RNA polymerase II within active genes. To explore the interplay between these modifications in transcribed noncoding well coding sequences, we analyzed modification and chromatin structure at high resolution across 300 kb human chromosome 11, including β-globin locus which extensively intergenic regions. Monomethylated H3K4, K9, K36 were broadly distributed, while hypermethylated forms...
Immunoglobulin E (IgE) plays a key role in allergic asthma and is clinically validated target for monoclonal antibodies. Therapeutic anti-IgE antibodies block the interaction between IgE Fc epsilon (Fcε) receptor, which eliminates or minimizes phenotype but does not typically curtail ongoing production of by B cells. We generated high-affinity (MEDI4212) that have potential to both neutralize soluble eliminate IgE-expressing B-cells through antibody-dependent cell-mediated cytotoxicity....
Selecting the most appropriate protein sequences is critical for precision drug design. Here we describe Haplosaurus, a bioinformatic tool computation of haplotypes. Haplosaurus computes haplotypes from pre-existing chromosomally-phased genomic variation data. Integration into Ensembl resource provides rapid and detailed retrieval. Using build database unique 1000 Genomes dataset reflecting real-world sequence variability their prevalence. For one in seven genes, common haplotype differs...
We examined DNA methylation throughout the endogenous murine testis-specific phosphoglycerate kinase (Pgk2) gene and in human PGK2 promoter/CAT reporter transgenes mouse spermatogenic cells before, during, following period of active transcription this gene. observed gradual development a domain demethylation beginning over promoter then expanding approximately 1 kilobase each direction within Pgk2 This develops absence replication precedes other molecular changes that potentiate...
Intratumor heterogeneity can confound the results of mutation analyses in oncodriver genes using traditional methods thereby challenging application targeted cancer therapy strategies for patients Ultradeep sequencing detect low frequency and expanded clonal mutations primary tumors to better inform treatment decisions. KRAS coding exons 61 treatment-naive colorectal (CRC) KRAS, EGFR, ALK, MET lung from three Chinese non-small cell (NSCLC) were sequenced ultradeep methods. Forty-one percent...
The G-protein coupled chemokine (C-X-C motif) receptor CXCR4 is linked to cancer, HIV, and WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. While reported be overexpressed in multiple human cancer types many hematological cell lines, we have observed poor vitro surface expression of solid tumor lines. We explore further the possible factors pathways involved regulating expression. Here, showed that MEK-ERK signaling pathway NFAT3 transcriptional factor plays a novel...
Establishment and maintenance of differential chromatin structure between transcriptionally competent repressed genes are critical aspects transcriptional regulation. The elements mechanisms that mediate formation these states in vivo not well understood. To examine the role promoter maintaining DNA methylation patterns active X-linked HPRT locus, 323 bp endogenous human (from position -222 to +102 relative translation start site) was replaced by plasmid sequences homologous recombination...
Non-natural amino acids (nnAA) contain unique functional moieties that greatly expand the available tool set for protein engineering. But incorporation of nnAAs requires function an orthogonal aminoacyl tRNA synthetase/tRNA pair. Stable cell lines expressing these components have been shown capable producing gram per liter levels antibodies with nnAAs. However, little has reported on genetic makeup cells. To gain a better understanding minimal requirements efficient nnAA we developed qPCR...
Abstract Intratumor heterogeneity can confound the results of mutation analyses in oncodriver genes using traditional methods thereby challenging application targeted cancer therapy strategies for patients. Ultradeep sequencing detect low frequency and expanded clonal mutations primary tumors to better inform treatment decisions. KRAS coding exons 61 treatment-naïve colorectal (CRC) KRAS, EGFR, ALK, MET lung from three Chinese non-small cell (NSCLC) patients were sequenced ultradeep methods....
Abstract The G-protein coupled chemokine (C-X-C motif) receptor CXCR4 is linked to cancer, HIV, and WHIM (Warts, Hypogammaglobulinemia, Infections, Myelokathexis) syndrome. While widely studied characterized extensively be over-expressed in multiple human tumor tissues, we have seen poor surface expression many solid cell lines vitro. To better understand how regulated, cells grown under 3-D spheroid conditions were compared normal adherent culturing conditions. When cultured as 3D...
<p>Supplementary methods and materials, Supplemental Figures</p>
<p>Supplementary methods and materials, Supplemental Figures</p>
<div>AbstractPurpose:<p>Antibody–drug conjugates (ADC) utilizing noncleavable linker drugs have been approved for clinical use, and several are in development targeting solid hematologic malignancies including multiple myeloma. Currently, there no reliable biomarkers of activity these ADCs other than presence the targeted antigen. We observed that certain cell lines innately resistant to such ADCs, sought uncover underlying mechanism resistance.</p>Experimental...
<div>AbstractPurpose:<p>Antibody–drug conjugates (ADC) utilizing noncleavable linker drugs have been approved for clinical use, and several are in development targeting solid hematologic malignancies including multiple myeloma. Currently, there no reliable biomarkers of activity these ADCs other than presence the targeted antigen. We observed that certain cell lines innately resistant to such ADCs, sought uncover underlying mechanism resistance.</p>Experimental...
Abstract Antibody-drug conjugates (ADCs) combine a monoclonal antibody with potent cytotoxic drug to preferentially eliminate antigen-positive cells for the treatment of cancer. ADCs bearing non-cleavable warheads such as pyrrolobenzodiazepine (PBD) SG3376 rely upon lysosomal degradation release warhead. Here we sought identify mechanism membrane transport following these membrane-insoluble warheads. We used multiplexed RT-PCR screen compare expression 43 membrane-specific genes in cell...