A5036550290- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Calcium signaling and nucleotide metabolism
- RNA modifications and cancer
- Toxin Mechanisms and Immunotoxins
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- RNA regulation and disease
- DNA Repair Mechanisms
- Chromatin Remodeling and Cancer
- Plant Virus Research Studies
- Genomics and Chromatin Dynamics
- Circular RNAs in diseases
- Electrostatic Discharge in Electronics
- Autophagy in Disease and Therapy
- CRISPR and Genetic Engineering
- Integrated Circuits and Semiconductor Failure Analysis
- Mosquito-borne diseases and control
- SARS-CoV-2 and COVID-19 Research
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- Cancer-related molecular mechanisms research
- Advancements in Semiconductor Devices and Circuit Design
Johns Hopkins Medicine
2016-2025
Johns Hopkins University
2016-2025
Cleveland Clinic
2023-2024
Akron General Medical Center
2023-2024
Sidney Kimmel Comprehensive Cancer Center
2019-2024
Interface (United States)
2024
Bloomberg (United States)
2024
Summa Health System
2008-2014
University of Baltimore
2012
Massachusetts Institute of Technology
2005-2011
Argonaute proteins associate with microRNAs (miRNAs) that bind mRNAs through partial base-pairings to primarily repress translation in animals. A fraction of and miRNAs biochemically cosediment polyribosomes, yet another paradoxically accumulates ribosome-free processing bodies (PBs) the cytoplasm. In this report, we give a quantitative account protein localization dynamics living cells different cellular states. We find majority is distributed diffusely cytoplasm, and, when are subjected...
ADP‐ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage viral infection is involved intra‐ extracellular signaling, chromatin transcriptional regulation, protein biosynthesis, cell death. ADP‐ribosylation catalyzed ADP‐ribosyltransferases (ARTs), which transfer ADP‐ribose from NAD + onto substrates. The modification, occurs as mono‐ or poly‐ADP‐ribosylation, reversible due...
Significance Viral outbreaks can be sudden and result in devastating social economic consequences. Chikungunya virus (CHIKV) of rash, arthritis, neurologic disease have occurred Africa, Asia, Europe, the Americas. There are no licensed vaccines to prevent or drugs treat CHIKV infection, mechanisms generation poorly understood. Here, we identify a macrodomain-containing protein with enzymatic ADP-ribosylhydrolase activity that is critical for virulence mammals define substrate specificity...
During mitosis, chromosomes are highly condensed and transcription is silenced globally. One explanation for transcriptional repression the reduced accessibility of factors. To directly test this hypothesis to investigate dynamics mitotic chromatin, we evaluate exchange kinetics several RNA polymerase I factors nucleosome components on chromatin in living cells. We demonstrate that these rapidly off ribosomal DNA clusters varies at different phases mitosis. In addition, component H1c-GFP...
Distinct properties of poly(ADP-ribose)-including its structural diversity, nucleation potential, and low complexity, polyvalent, highly charged nature-could contribute to organizing cellular architectures. Emergent data indicate that poly(ADP-ribose) aids in the formation nonmembranous structures, such as DNA repair foci, spindle poles, RNA granules. Informatics analyses reported here show granule proteins enriched for complexity regions, which aid self-assembly, are preferentially modified...
Alphaviruses are plus-strand RNA viruses that cause encephalitis, rash, and arthritis. The nonstructural protein (nsP) precursor polyprotein is translated from genomic processed into four nsPs. nsP3 has a highly conserved macrodomain (MD) binds ADP-ribose (ADPr), which can be conjugated to as posttranslational modification involving transfer of ADPr NAD+ by poly polymerases (PARPs). nsP3MD also removes mono ADP-ribosylated (MARylated) substrates. To determine aspects alphavirus replication...
Poly(ADP-ribose), or PAR, is a cellular polymer implicated in DNA/RNA metabolism, cell death, and stress response via its role as post-translational modification, signaling molecule, scaffolding element. PAR synthesized by family of proteins known poly(ADP-ribose) polymerases, PARPs, which attach polymers to various amino acids substrate proteins. The nature these (large, charged, heterogeneous, base-labile) has made attachment sites difficult study mass spectrometry. Here we propose new...
Somatic inactivating mutations in ARID1A, a component of the SWI/SNF chromatin remodeling complex, are detected various types human malignancies. Loss ARID1A compromises DNA damage repair. The induced burden may increase reliance on PARP-dependent repair cancer cells to maintain genome integrity and render susceptibility PARP inhibitor therapy.Experimental Design: Isogenic ARID1A-/- wild-type cell lines were used for assessing response, compactness, profiling global serine/threonine...
MicroRNA (miRNA) is a type of noncoding RNA that can repress the expression target genes through posttranscriptional regulation. In addition to numerous physiologic roles for miRNAs, they play an important role in pathophysiologic processes affecting cardiovascular health. Previously, we reported nuclear encoded microRNA (miR-181c) present heart mitochondria, and importantly, its overexpression affects mitochondrial function by regulating gene expression.To investigate further how miR-181...
Significance Alphaviruses are mosquito-borne RNA viruses that cause rash, arthritis, and neurologic disease. Despite a continued risk of outbreaks, there no licensed interventions for any alphavirus. For progress in control, an understanding the molecular targets affect virus replication virulence is essential. This paper characterizes conserved macrodomain factor nonstructural protein 3 (nsP3). We discovered ADP-ribosylhydrolase activity critical controlling composition cellular...