A5066462727- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Insect symbiosis and bacterial influences
- Mosquito-borne diseases and control
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- RNA Research and Splicing
- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Genomic variations and chromosomal abnormalities
- Single-cell and spatial transcriptomics
- Viral Infections and Outbreaks Research
- RNA regulation and disease
- Congenital heart defects research
- Invertebrate Immune Response Mechanisms
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer-related Molecular Pathways
- Developmental Biology and Gene Regulation
- Cardiac Fibrosis and Remodeling
- SARS-CoV-2 and COVID-19 Research
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
University of Maryland, Baltimore
2021-2025
National Institute of Diabetes and Digestive and Kidney Diseases
2014-2022
University of Baltimore
2022
National Institutes of Health
2014-2021
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2019-2021
Rutgers, The State University of New Jersey
2010-2012
Rutgers Sexual and Reproductive Health and Rights
2010
Abstract Background SARS-CoV-2 causes COVID-19 which has a widely diverse disease profile. The mechanisms underlying its pathogenicity remain unclear. We set out to identify the pathogenic proteins that through host interactions cause cellular damages symptomatology. Methods examined each of individual for their cytotoxicity in HEK 293 T cells and subcellular localization COS-7 cells. also used Mass-Spec Affinity purification interacting with Orf6 protein tested drug could inhibit specific...
A generally accepted approach to the analysis of RNA-Seq read count data does not yet exist. We sequenced mRNA 726 individuals from Drosophila Genetic Reference Panel in order quantify differences gene expression among single flies. One our experimental goals was identify optimal for detection differential factors we varied experiment: genotype, environment, sex, and their interactions. Here evaluate three different filtering strategies, eight normalization methods, two statistical...
Abstract Background Structural rearrangements of the genome resulting in genic imbalance due to copy number change are often deleterious at organismal level, but common immortalized cell lines and tumors, where they may be an advantage cells. In order explore biological consequences changes Drosophila genome, we resequenced genomes 19 tissue-culture generated RNA-Seq profiles. Results Our work revealed dramatic duplications deletions all lines. We found three evidence indicating that were...
Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature the slow turnover of NPC components complicates investigations how individual nucleoporins act in these diverse processes. To address this question, we apply an A uxin- I nduced D egron (AID) system to distinguish roles basket NUP153, NUP50 TPR. Acute depletion TPR causes rapid pronounced changes...
Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts. Insects such as mosquitos act vectors for many devastating human viruses Dengue, West Nile, and Zika. Remarkably, infection provides hosts with resistance to arboviruses thereby rendering the insects ineffective vectors. To utilize effectively tool against vector-borne better understanding host-Wolbachia relationship needed. investigate Wolbachia-insect interactions we used Wolbachia/Drosophila model...
Abstract SARS-CoV-2 infection causes COVID-19, a severe acute respiratory disease associated with cardiovascular complications including long-term outcomes. The presence of virus in cardiac tissue patients COVID-19 suggests this is direct, rather than secondary, effect infection. Here, by expressing individual proteins the Drosophila heart, we demonstrate interaction Nsp6 host MGA/MAX complex (MGA, PCGF6 and TFDP1). Complementing transcriptomic data from fly heart reveal that blocks...
Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and genetic pathway discovery via dose-dependent suppressor enhancer screens. More recently, it has become clear that deviations from normal gene dosage associated with multiple disorders in a range of species including humans. While we beginning understand some the transcriptional effects brought about changes chromosome rearrangement breakpoints them, much this work relies on...
SARS-CoV-2 causes COVID-19 with a widely diverse disease profile that affects many different tissues. The mechanisms underlying its pathogenicity in host organisms remain unclear. Animal models for studying the of proteins are lacking.Using bioinformatic analysis, we found 90% virus-host interactions involve human conserved Drosophila. Therefore, generated series transgenic fly lines individual genes, and used Gal4-UAS system to express these viral genes Drosophila study their...
Spike-in RNAs are valuable controls for a variety of gene expression measurements. The External RNA Controls Consortium developed test sets that were used in number published reports. Here we provide an authoritative table summarizes, updates, and corrects errors the version ultimately resulted certified Standard Reference Material 2374. We have noted existence anti-sense material, corrected sub-pool memberships, commented on control displayed inconsistent behavior.
Gene regulatory networks (GRNs) describe relationships between transcription factors (TFs) and their target genes. Computational methods to infer GRNs typically combine evidence across different conditions context-agnostic networks. We develop a method, Network Reprogramming using EXpression (NetREX), that constructs context-specific GRN given expression data prior network. NetREX remodels the network obtain topology provides best explanation for data. Because utilizes topology, we also...
Vertebrate postembryonic development is regulated by thyroid hormone (T3). Of particular interest anuran metamorphosis, which offers several unique advantages for studying the role of T3 and its two nuclear receptor genes, TRα TRβ, during development. We have recently generated TR double knockout (TRDKO) Xenopus tropicalis animals reported that essential completion metamorphosis. Furthermore, TRDKO tadpoles are stalled at climax metamorphosis before eventual death. Here we show intestine...
Drosophila is an important model for studying heart development and disease. Yet, single-cell transcriptomic data of its developing have not been performed. Here, we report profiling the entire fly using ∼3000 Hand-GFP embryos collected at five consecutive developmental stages, ranging from bilateral migrating rows cardiac progenitors to a fused tube. The revealed six distinct cell types in embryonic heart: cardioblasts, both Svp+ Tin+ subtypes; pericardial (PC) that can be distinguished by...
The RB and E2F proteins play important roles in the regulation of cell division, death, development by controlling expression genes involved these processes. mechanisms repression retinoblastoma protein (pRB) have been extensively studied at cycle-regulated promoters. However, little is known about developmentally regulated E2F/RB genes. Here, we taken advantage simplicity pathway flies to inspect differentiation-specific target These are repressed dE2F2/RBF a recently identified...
Macromolecular transport between the nucleus and cytoplasm is mediated through Nuclear Pore Complexes (NPCs), which are built from multiple copies of roughly 34 distinct proteins, called nucleoporins 1–3 . Models NPC depict it as a composite several sub-domains that have been named outer rings, inner ring, cytoplasmic fibrils nuclear basket. While has extensively studied, roles individual within NPCs their functional interactions remain poorly understood. Here, we applied rapid degron system...
E2F and RB proteins regulate the expression of genes involved in cell cycle progression, apoptosis, differentiation, development.Recent studies indicate that they function as part an evolutionarily conserved multiprotein complex termed dREAM/ DREAM/LINC.Here we characterize role Drosophila complex, dREAM, regulation differentiation-specific target actively proliferating cells.These are regulated differently from cycle-related targets, do not depend on activation, E2F/RB repression is...
Abstract DNA copy number variation is associated with many high phenotypic heterogeneity disorders. We systematically examined the impact of Drosophila melanogaster deletions on gene expression profiles to ask whether increased variability owing reduced dose might underlie this heterogeneity. Indeed, we found that one-dose genes have higher relative two-dose genes. then asked increase in could be explained by intrinsic noise within cells due stochastic biochemical events, or extrinsic...
The maintenance of the intestinal epithelium is ensured by controlled proliferation stem cells (ISCs) and differentiation their progeny into various cell types, including enterocytes (ECs) that both mediate nutrient absorption provide a barrier against pathogens. signals regulate transition proliferative ISCs differentiated ECs are not fully understood. IRBIT an evolutionarily conserved protein regulates ribonucleotide reductase (RNR), enzyme critical for generation DNA precursors. Here, we...
Strain differences have been reported for motor behaviors, and only a subset of spinal cord injury (SCI) patients develop neuropathic pain, implicating genetic or genomic contribution to this condition. Here, we evaluated neuropsychiatric behaviors in A/J, BALB/c, C57BL/6 male mice tested alterations following SCI. A/J BALB/c naive showed significantly less locomotor activity greater anxiety-like behavior than mice. Although SCI elicited dysfunction, the best worst post-traumatic recovery,...
In animals with XY sex chromosomes, X-linked genes from a single X chromosome in males are imbalanced relative to autosomal genes. To minimize the impact of genic imbalance male Drosophila, there is dosage compensation complex (MSL) that equilibrates gene expression autosomes. There other potential contributions compensation. Hemizygous located repressive chromatin domains often derepressed. If this homolog-dependent repression occurs on X, which has no pairing partner, then derepression...
Ran's GTPase-activating protein (RanGAP) is tethered to the nuclear envelope (NE) in multicellular organisms. We investigated consequences of RanGAP localization human tissue culture cells and Drosophila. In cells, disruption RanGAP1 NE surprisingly has neither obvious impacts on viability nor nucleocytoplasmic transport a model substrate. Drosophila, we identified region within nucleoporin dmRanBP2 required for direct tethering dmRanGAP NE. A mutant lacking this shows no apparent growth...
Abstract The inference of Gene Regulatory Networks (GRNs) is one the key challenges in systems biology. Leading algorithms utilize, addition to gene expression, prior knowledge such as Transcription Factor (TF) DNA binding motifs or results TF experiments. However, typically incomplete, therefore, integrating it with expression infer GRNs remains difficult. To address this challenge, we introduce NetREX-CF—Regulatory Network Reconstruction using EXpression and Collaborative Filtering—a GRN...
Abstract Wolbachia is an intracellular bacterium that infects a remarkable range of insect hosts. Insects such as mosquitos act vectors for many devastating human viruses Dengue, West Nile, and Zika. Remarkably, infection provides hosts with resistance to arboviruses thereby rendering the insects ineffective vectors. To utilize effectively tool against vector-borne better understanding host- relationship needed. investigate -insect interactions we used Wolbachia/Drosophila model genetically...