A5004035650- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- RNA regulation and disease
- DNA Repair Mechanisms
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Nuclear Structure and Function
- DNA and Nucleic Acid Chemistry
- Genetics and Neurodevelopmental Disorders
- Cholesterol and Lipid Metabolism
- Ubiquitin and proteasome pathways
- PARP inhibition in cancer therapy
- Genomics and Phylogenetic Studies
- Plant Molecular Biology Research
- Drug Transport and Resistance Mechanisms
- Developmental Biology and Gene Regulation
- Plant biochemistry and biosynthesis
- Lung Cancer Research Studies
- 14-3-3 protein interactions
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
University of Illinois Urbana-Champaign
2022-2025
Urbana University
2025
Stanford University
2015-2022
Cardiovascular Institute of the South
2017
Emory University
2009-2015
Pediatrics and Genetics
2015
AID Atlanta
2012-2013
Chromosome conformation capture studies suggest that eukaryotic genomes are organized into structures called topologically associating domains. The borders of these domains highly enriched for architectural proteins with characterized roles in insulator function. However, a majority protein binding sites localize within topological domains, suggesting associated domain represent functionally different subclass regulatory elements. How established and what differentiates border-associated...
Several multiprotein DNA complexes capable of insulator activity have been identified in Drosophila melanogaster , yet only CTCF, a highly conserved zinc finger protein, and the transcription factor TFIIIC shown to function mammals. CTCF is involved diverse nuclear activities, recent studies suggest that proteins with which it associates sequences targets may underlie these various roles. Here we show homolog (dCTCF) aligns genome other such as Suppressor Hairy wing [SU(HW)] Boundary Element...
Rationale: Recent advances have improved our ability to generate cardiomyocytes from human induced pluripotent stem cells (hiPSCs) and embryonic (hESCs). However, understanding of the transcriptional regulatory networks underlying early stages (ie, mesoderm cardiac mesoderm) cardiomyocyte differentiation remains limited. Objective: To characterize transcriptome chromatin accessibility during hiPSCs hESCs. Methods Results: We profiled temporal changes in at genome-wide levels derived 2 hiPSC...
Nup98 is a glycine-leucine-phenylalanine-glycine (GLFG) repeat–containing nucleoporin that, in addition to nuclear transport, contributes multiple aspects of gene regulation. Previous studies revealed its dynamic localization within intranuclear structures known as GLFG bodies. Here we show that the mammalian Nup107-160 complex (Y-complex), major scaffold module pore, together with partner Elys, colocalizes The frequency and size bodies vary among HeLa sublines, find an increased level...
Transcription regulation is mediated by enhancers that bind sequence-specific transcription factors, which in turn interact with the promoters of genes they control. Here, we show JIL-1 kinase present at both and ecdysone-induced Drosophila genes, where it phosphorylates Ser10 Ser28 residues histone H3. also required for CREB binding protein (CBP)-mediated acetylation Lys27, a well-characterized mark active enhancers. The presence these proteins results establishment H3K9acS10ph H3K27acS28ph...
DREF was first characterized for its role in the regulation of transcription genes encoding proteins involved DNA replication and found to interact with sequences similar recognition motif BEAF-32 insulator protein. Insulators are DNA-protein complexes that mediate intra- inter-chromosome interactions. Several DNA-binding have been described Drosophila, including BEAF-32, dCTCF Su(Hw). Here we find co-localize at same genomic sites, but their enrichment shows an inverse correlation....
Abstract RNA polymerase III (Pol III) includes two alternate isoforms, defined by mutually exclusive incorporation of subunit POLR3G (RPC7α) or POLR3GL (RPC7β), in mammals. The contributions and to transcription potential has remained poorly defined. Here, we discover that loss is accompanied a restricted repertoire genes transcribed Pol III. Particularly sensitive snaR-A, small noncoding implicated cancer proliferation metastasis. Analysis isoform biases downstream chromatin features...
The human genome is hierarchically organized into local and long-range structures that help shape cell-type-specific transcription patterns. Transfer RNA (tRNA) genes (tDNAs), which are transcribed by polymerase III (RNAPIII) encode molecules responsible for translation, dispersed throughout the and, in many cases, linearly genomic clusters with other tDNAs. Whether location three-dimensional organization of tDNAs contribute to activity these has remained difficult address, due part unique...
Brd4 is a double bromodomain protein that has been shown to interact with acetylated histones regulate transcription by recruiting Positive Transcription Elongation Factor b the promoter region. also involved in gene bookmarking during mitosis and therapeutic target for treatment of acute myeloid leukemia. The Drosophila melanogaster homologue called Fs(1)h and, like its vertebrate counterpart, encodes different isoforms. We have used ChIP-seq examine genome-wide distribution are able...
ABSTRACT Although immune therapy has seen significant advances, the majority of breast and other solid tumors do not respond or quickly develop de novo resistance. One factor driving resistance is highly suppressive myeloid cells (MCs) such as macrophages. Previous work established clinical links between cholesterol cancer outcome, that MC function can be regulated through disruption in metabolism. Thus, we screened for proteins were expressed MCs, involved homeostasis whose expression was...
Abstract Although significant strides have been made in immune-targeting therapies such as immune checkpoint blockade (ICB), many solid tumors do not respond and acquired resistance is common, especially for metastatic disease. For example, ICB only FDA approved breast cancer of the triple negative subtype (TNBC) where stain positive PD-L1, but even amongst this cohort, response rate modest. multifactorial, a major driver thought to be contributed by suppressive myeloid cells, macrophages....
Abstract 13- cis -retinoic acid (isotretinoin, INN) is an oral pharmaceutical drug used for the treatment of skin acne, and also a known teratogen. In this study, molecular mechanisms underlying INN-induced developmental toxicity during early cardiac differentiation were investigated using both human induced pluripotent stem cells (hiPSCs) embryonic (hESCs). Pre-exposure hiPSCs hESCs to sublethal concentration INN did not influence cell proliferation pluripotency. However, mesodermal was...
The transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) pathways transduce extracellular signals into tissue-specific transcriptional responses. During this process, signaling effector Smad proteins translocate the nucleus to direct changes in transcription, but how where they localize DNA remain important questions. We have mapped Drosophila TGF-β factors Mad, dSmad2, Medea, Schnurri genome-wide Kc cells find that numerous sites for these overlap with architectural...
As our closest living relatives, non-human primates uniquely enable explorations of human health, disease, development, and evolution. Considerable effort has thus been devoted to generating induced pluripotent stem cells (iPSCs) from multiple primate species. Here, we establish improved culture methods for chimpanzee (Pan troglodytes) pig-tailed macaque (Macaca nemestrina) iPSCs. Such iPSCs spontaneously differentiate in conventional conditions, but can be readily propagated by inhibiting...
RNA polymerase III (Pol III) subunit RPC7α, which is encoded by POLR3G in humans, has been linked to both tumor growth and metastasis. Accordantly, high expression a negative prognostic factor multiple cancer subtypes. To date, the mechanisms underlying upregulation have remained poorly defined. We performed large-scale genomic survey of mRNA chromatin signatures predict drivers cancer. Our uncovers positive determinants expression, including gene-internal super-enhancer bound with...