- RNA Research and Splicing
- RNA modifications and cancer
- Selenium in Biological Systems
- RNA and protein synthesis mechanisms
- Cancer Research and Treatments
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- Polyamine Metabolism and Applications
- Animal Virus Infections Studies
- Trace Elements in Health
- Ubiquitin and proteasome pathways
- Genetic Neurodegenerative Diseases
- Redox biology and oxidative stress
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Acute Myeloid Leukemia Research
- Nitrogen and Sulfur Effects on Brassica
- Aortic aneurysm repair treatments
- Genomics and Chromatin Dynamics
- Cardiovascular and Diving-Related Complications
- Traumatic Brain Injury and Neurovascular Disturbances
- Cancer-related gene regulation
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Cell Adhesion Molecules Research
University of Florida
2017-2024
Florida College
2018-2024
Cleveland Clinic
2011-2018
University of Toronto
2013-2015
Cleveland Clinic Lerner College of Medicine
2007-2014
Cerner (United States)
2014
Case Western Reserve University
2011
Charoenkrung Pracharak Hospital
2007
Genetic variations across the SARS-CoV-2 genome may influence transmissibility of virus and host's anti-viral immune response, in turn affecting frequency variants over time. In this study, we examined adjacent amino acid polymorphisms nucleocapsid (R203K/G204R) that arose on background spike D614G change describe how strains harboring these changes became dominant circulating globally.Deep-sequencing data from public databases clinical samples were analyzed to identify map genetic...
Abstract The cardiovascular system is strongly impacted by the hazards of spaceflight. Astronauts spending steadily increasing lengths time in microgravity are subject to deconditioning resulting loss vascular tone, reduced total blood volume, and diminished cardiac output. Appreciating mechanisms which cells vasculature altered during spaceflight will be integral understanding combating these deleterious effects as human presence space advances. In this study, we performed RNA-Seq analysis...
The expression of selenoproteins requires the translational recoding UGA stop codon to selenocysteine. In eukaryotes, this an RNA stem loop structure in 3′-untranslated region, termed a selenocysteine insertion sequence (SECIS), and SECIS-binding protein 2 (SBP2). This study implicates SBP2 dictating hierarchy selenoprotein expression, because it is first show that distinguishes between SECIS elements vitro. Using electrophoretic mobility shift assays, we demonstrate naturally occurring...
Selenoprotein S (SelS) is a 189 amino acid trans-membrane protein that plays an important yet undefined role in the unfolded response. It has been proposed SelS may function as reductase, with penultimate selenocysteine (Sec188) residue participating selenosulfide bond cysteine (Cys174). Cotranslational incorporation of Sec into depends on recoding UGA codon, which requires Selenocysteine Insertion Sequence (SECIS) element 3′UTR transcript. Here we identify multiple mechanisms regulate...
Abstract Background Genetic variations across the SARS-CoV-2 genome may influence transmissibility of virus and host’s anti-viral immune response, in turn affecting frequency variants over-time. In this study, we examined adjacent amino acid polymorphisms nucleocapsid (R203K/G204R) that arose on background spike D614G change describe how strains harboring these changes became dominant circulating globally. Methods Deep sequencing data from public databases clinical samples were analyzed to...
Selenium, a micronutrient, is primarily incorporated into human physiology as selenocysteine (Sec). The 25 Sec-containing proteins in humans are known selenoproteins. Their synthesis depends on the translational recoding of UGA stop codon to allow Sec insertion. This requires stem-loop structure 3' untranslated region eukaryotic mRNAs Selenocysteine Insertion Sequence (SECIS). SECIS recognized by SECIS-binding protein 2 (SBP2) and this RNA:protein interaction essential for occur. Genetic...
Short tandem repeats (STRs) are prone to expansion mutations that cause multiple hereditary neurological and neuromuscular diseases. To study pathomechanisms using mouse models recapitulate the tissue specificity developmental timing of an STR gene, we used rolling circle amplification CRISPR/Cas9-mediated genome editing generate Dmpk CTG (CTG exp ) knockin myotonic dystrophy type 1 (DM1). We demonstrate skeletal muscle myoblasts brain choroid plexus epithelial cells particularly susceptible...
eIF4a3, a DEAD-box protein family member, is component of the exon junction complex which assembles on spliced mRNAs. The also acts as transcript-selective translational repressor selenoprotein synthesis during selenium deficiency. Selenocysteine (Sec) incorporation into selenoproteins requires Sec Insertion Sequence (SECIS) element in 3′ untranslated region. During deficiency, eIF4a3 binds SECIS elements from non-essential selenoproteins, preventing insertion. We identified molecular...
ABSTRACT Skeletal muscle tissue is severely affected in myotonic dystrophy type 1 (DM1) patients, characterised by weakness, myotonia and immaturity the most severe congenital form of disease. Previously, it was not known at what stage during myogenesis DM1 phenotype appears. In this study we differentiated healthy human embryonic stem cells to myoblasts myotubes compared their differentiation potential using a comprehensive multi-omics approach. We found be abnormal with altered myotube...
Stroke is a major cause of disability for adults over 40 years age. While research into animal models has prioritized treatments aimed at diminishing post-stroke damage, no studies have investigated the response to severe stroke injury in highly regenerative adult mammal. Here we investigate effects transient ischemia on spiny mice, Acomys cahirinus, due their ability regenerate multiple tissues without scarring. Transient middle cerebral artery occlusion was performed and showed rapid...
The human selenoproteome is composed of approximately 25 selenoproteins, which cotranslationally incorporate selenocysteine, the 21st amino acid. Selenoprotein expression requires an unusual translation mechanism, as selenocysteine encoded by UGA stop codon. SECIS-binding protein 2 (SBP2) essential component insertion machinery. SBP2 also only factor known to differentiate among selenoprotein mRNAs, thereby modulating relative individual selenoproteins. Here, we show that varies widely...
Balanced processing of HIV-1 RNA is critical to virus replication and regulated by host factors. In this report, we demonstrate that overexpression either Tra2α or Tra2β results in a marked reduction Gag/ Env expression, an effect associated with changes accumulation, altered viral splice site usage, block export genomic RNA. A natural isoform (Tra2ß3), lacking the N-terminal RS domain, also suppressed expression but had different effects on processing. The functional differences between...
In vivo RNA structure analysis has become a powerful tool in molecular biology, largely due to the coupling of an increasingly diverse set chemical approaches with high-throughput sequencing. This resulted transition from single target transcriptome-wide approaches. However, these methods require sequencing depths that preclude studying low abundance targets, which are not sufficiently captured Here we demonstrate enrichment targets before reverse transcription broadens range molecules...
Background Balanced processing of HIV-1 RNA is critical to virus replication and regulated by host factors such as SR proteins. To examine the role SR-related proteins Tra2a Tra2b in regulating viral gene expression, we used both overexpression depletion analysis how these impacted splicing, transport expression mutation identify protein domains involved.
ABSTRACT Refractory disease is the greatest challenge in acute myeloid leukaemia (AML). Previously, we found vascular-associated AML cells as a source for refractory disease. In this study use bioassay of co-cultured on bone marrow-derived endothelial (BMECs) to screen 31 million compounds within mixture-based synthetic combinatorial library followed by deconvolution leading identification novel polyamine sulfonamide that selectively toxic AML. Using three distinct proteomics methods...