A5049555114- PI3K/AKT/mTOR signaling in cancer
- Dermatology and Skin Diseases
- Psoriasis: Treatment and Pathogenesis
- RNA Research and Splicing
- RNA modifications and cancer
- Nail Diseases and Treatments
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- SARS-CoV-2 detection and testing
- Acute Myeloid Leukemia Research
- Viral Infectious Diseases and Gene Expression in Insects
- Animal Virus Infections Studies
- Cancer Cells and Metastasis
- CRISPR and Genetic Engineering
- Influenza Virus Research Studies
- Bacillus and Francisella bacterial research
- Environmental DNA in Biodiversity Studies
- Renal and related cancers
- Gut microbiota and health
- Gastric Cancer Management and Outcomes
Johns Hopkins University Applied Physics Laboratory
2020-2024
New York University
2015-2023
NYU Langone’s Laura and Isaac Perlmutter Cancer Center
2020
York University
2020
American Association For Cancer Research
2019
NYU Langone Health
2018
University of Kansas
2013-2017
Translation initiation of most mammalian mRNAs is mediated by a 5' cap structure that binds eukaryotic factor 4E (eIF4E). However, inactivation eIF4E does not impair translation many capped mRNAs, suggesting an unknown alternate mechanism may exist for cap-dependent but eIF4E-independent translation. We show DAP5, eIF4GI homolog lacks binding, utilizes eIF3d to facilitate approximately 20% mRNAs. Genome-wide transcriptomic and translatomic analyses indicate DAP5 required transcription...
Cancer cell plasticity enables survival in harsh physiological environments and fate transitions such as the epithelial-to-mesenchymal transition (EMT) that underlies invasion metastasis. Using genome-wide transcriptomic translatomic studies, an alternate mechanism of cap-dependent mRNA translation by DAP5/eIF3d complex is shown to be essential for metastasis, EMT, tumor directed angiogenesis. carries out selective mRNAs encoding EMT transcription factors regulators, migration integrins,...
Abstract Regulatory T cells (Treg cells) inhibit effector and maintain immune system homeostasis. Treg cell maturation in peripheral sites requires inhibition of protein kinase mTORC1 TGF-beta-1 (TGF-beta). While synthesis, downregulates it, leaving unanswered how achieve essential mRNA translation for development suppression activity. Using human CD4 + differentiated culture genome-wide transcription profiling, here we report that TGF-beta transcriptionally reprograms naive to express...
Skin, the largest organ of human body by weight, hosts a diversity microorganisms that can influence health. The microbial residents skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various disorders. Still, much remains to be discovered terms pathways influenced microorganisms, as well higher-level properties impacted through these microbe-host interactions. Towards this direction, recent efforts using mouse models point...
The ability to predict the evolution of a pathogen would significantly improve control, prevent, and treat disease. Machine learning, however, is yet be used evolutionary progeny virus. To address this gap, we developed novel machine learning framework, named MutaGAN, using generative adversarial networks with sequence-to-sequence, recurrent neural generator accurately genetic mutations future biological populations. MutaGAN was trained generalized time-reversible phylogenetic model protein...
The majority of breast cancers expresses the estrogen receptor (ER + ) and is treated with anti-estrogen therapies, particularly tamoxifen in premenopausal women. However, resistance responsible for a large proportion cancer deaths. Using small molecule inhibitors, phospho-mimetic proteins, tamoxifen-sensitive tamoxifen-resistant cells, patient-derived xenograft model, patient tumor tissues, genome-wide transcription translation studies, we show that involves selective mRNA translational...
The early COVID-19 pandemic was characterized by rapid global spread. In Maryland and Washington, DC, United States, more than 2500 cases were reported within 3 weeks of the first detection in March 2020. We aimed to use genomic sequencing understand initial spread SARS-CoV-2 — virus that causes region. analyzed 620 samples collected from Johns Hopkins Health System during 11–31, 2020, comprising 28.6% total DC. From these samples, we generated 114 complete viral genomes. Analysis genomes...
Gene interaction networks specify how genes interact to produce an organism's phenotype. These are often incomplete due absent or unobserved information. Predicting these missing links is critical for many applications, including genome-wide association studies and phenotype prediction. Efforts have previously applied graph neural (GNNs) this missing-link prediction problem, but techniques too limitations when the sparsity of very high. Here, we apply a novel feature engineering technique...
mTOR coordinates growth signals with metabolic pathways and protein synthesis is hyperactivated in many human cancers. exists two complexes: mTORC1, which stimulates protein, lipid, ribosome biosynthesis, mTORC2, regulates cytoskeleton functions. While known to be involved the DNA damage response, little actually regarding functions of mTORC1 compared mTORC2 this regard or respective impacts on transcriptional versus translational regulation. We show that are both required enact repair cell...
The mammalian DREAM complex is responsible for the transcriptional repression of hundreds cell-cycle-related genes in quiescence. How recruits chromatin-modifying entities to aid its remains unknown. Using unbiased proteomics analysis, we have uncovered a robust association between chromatin-associated Sin3B protein and complex. We determined that genetic inactivation results de-repression target during quiescence but insufficient allow quiescent cells resume proliferation. However,...
// Gizelka David-West 1,4,* , Amanda Ernlund 2,* Abhilash Gadi 2 and Robert J. Schneider 2,3 1 Division of Gynecologic Oncology, New York University School Medicine, York, NY, USA Department Microbiology, 3 Perlmutter Cancer Center, 4 Medical College, Westchester Hawthorne, * These authors have contributed equally to this work Correspondence to: Schneider, email: Robert.schneider@nyumc.org Keywords : mTOR; ovarian cancer; platinum resistance; translational regulation Received: October 31,...
Translatomics data, particularly genome-wide ribosome profiling and polysome profiling, provide multiple levels of gene regulatory information that can be used to assess general transcription translation, as well translational efficiency. The increasing popularity these techniques has resulted in algorithms detect regulation, typically distributed the form command line tools require a basic level programming ability. Additionally, due static nature current software, dynamic transcriptional...
Abstract Background The early COVID-19 pandemic has been characterized by rapid global spread. In the United States National Capital Region, over 2,000 cases were reported within three weeks of its first detection in March 2020. We aimed to use genomic sequencing understand initial spread SARS-CoV-2, virus that causes COVID-19, region. By correlating genetic information disease phenotype, we also gain insight into any correlation between viral genotype and case severity or transmissibility....
Background Cancers induce gene expression alterations in stroma surrounding tumors that supports cancer progression. However, it is actually not at all known the extent of altered stromal enacted by nor to which penetrates tissue. Presently, post-surgical "tumor-free" tissue determined be cancer-free based on solely morphological normality—a criteria has changed more than 100 years despite existence sophisticated data contrary. We therefore investigated breast alter three dimensions women...
An optimized, well-tested and validated targeted genomic sequencing-based high-throughput assay is currently not available ready for routine biodefense biosurveillance applications. Earlier, we addressed this gap by developing establishing baseline comparisons of a multiplex end-point Polymerase Chain Reaction (PCR) followed Oxford Nanopore Technology (ONT) based amplicon sequencing to real time PCR customized data processing. Here, expand upon effort identifying the optimal ONT library...
Common treatment for venous leg wounds includes topical wound dressings with compression. At each dressing change, are debrided and washed; however, the effect of washing procedure on microbiome has not been studied. We hypothesized that may alter microbiome. To characterize changes respect to washing, swabs from 11 patients chronic were sampled before after patient microbiomes characterized using 16S rRNA sequencing culturing. Microbiomes across samples prior typically polymicrobial but...
Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in model organism. One such oncogene, Musashi-1 (Msi-1), regulates translation mRNAs and is implicated promoting the colon other tissues. Msi-1 targets include tumor suppressor adenomatous polyposis coli (Apc), Wnt pathway antagonist lost ∼80% all colorectal cancers. Cell culture experiments have established target, thus positioning Apc as mutual...
Military trainees are at increased risk for infectious disease outbreaks because of the unique circumstances training environment (e.g., close proximity areas and physiologic/psychologic stress). Standard medical countermeasures in military settings include routine immunization influenza adenovirus) as well chemoprophylaxis [e.g., benzathine penicillin G (Bicillin) prevention group A streptococcal disease] pathogens associated with these settings. In a population U.S. Army Infantry trainees,...
BackgroundDuring the 2017–18 influenza season in USA, there was a high incidence of illness and mortality. However, no apparent antigenic change identified dominant H3N2 viruses, severity could not be solely attributed to vaccine mismatch. We aimed investigate whether altered virus properties resulting from gene reassortment were underlying causes increased case number disease associated with season.MethodsSamples included collected patients who prospectively recruited during 2016–17 seasons...
Abstract Background Skin, the largest organ of human body by weight, hosts a diversity microorganisms that can influence health. The microbial residents skin are now appreciated for their roles in host immune interactions, wound healing, colonization resistance, and various disorders. Still, much remains to be discovered terms pathways influenced microorganisms, as well higher-level properties impacted through these microbe-host interactions. Towards this direction, recent efforts using...
Meeting abstracts The immunological composition of the primary cancer, metastatic sites, and stromal tissue determine cancer progression treatment response. Breast cancers produce cytokines chemokines that attract polarize immune cells in a manner promotes disease
Abstract Regulatory T cells (Tregs) maintain immune system homeostasis in the organism. In tumor microenvironment, however, Tregs can hinder antitumor response. Treg maturation peripheral sites (pTregs) requires inhibition of protein kinase mTORC1, which paradoxically blocks mRNA translation. mTORC1 phosphorylates (inactivates) 4E-BP1, a negative regulator translation initiation factor eIF4E. When is active, 4E-BP1 hyperphosphorylated and releases eIF4E, then bind cap structure promote eIF4F...