A5055736876- Plant Molecular Biology Research
- RNA and protein synthesis mechanisms
- Machine Learning in Bioinformatics
- Gene Regulatory Network Analysis
- Protein Structure and Dynamics
- Bioinformatics and Genomic Networks
- Genetic Mapping and Diversity in Plants and Animals
- RNA regulation and disease
- Light effects on plants
- RNA Interference and Gene Delivery
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Natural Antidiabetic Agents Studies
- Plant Gene Expression Analysis
- Health and Lifestyle Studies
- Connexins and lens biology
- Cellular transport and secretion
- Phytochemistry and biological activities of Ficus species
- RNA Research and Splicing
- Circadian rhythm and melatonin
- Advanced biosensing and bioanalysis techniques
- Silk-based biomaterials and applications
- Genetic Associations and Epidemiology
- Mobile Health and mHealth Applications
- Diabetes Management and Education
North Carolina State University
2016-2024
Wave Life Sciences (United States)
2022-2024
Harvard University
2012-2014
Boston Children's Hospital
2012-2014
HealthPartners
2012-2014
Johnson University
2008
Advanced Pharma
2008
Although recent regulatory approval of splice-switching oligonucleotides (SSOs) for the treatment neuromuscular disease such as Duchenne muscular dystrophy has been an advance field, current SSO chemistries have shown limited clinical benefit due to poor pharmacology. To overcome limitations existing technologies, we engineered chimeric stereopure with phosphorothioate (PS) and phosphoryl guanidine-containing (PN) backbones. We demonstrate that these markedly improved pharmacology efficacy...
Abstract Herein, we report the systematic investigation of stereopure phosphorothioate (PS) and phosphoryl guanidine (PN) linkages on siRNA-mediated silencing. The incorporation appropriately positioned configured PS PN to N-acetylgalactosamine (GalNAc)-conjugated siRNAs based multiple targets (Ttr HSD17B13) increased potency durability mRNA silencing in mouse hepatocytes vivo compared with reference molecules clinically proven formats. observation that same modification pattern had...
Significance The effects of warmer nighttime temperatures (WNT) on crops are one poorly understood dimension climate change. WNT result from the asymmetrical increase in versus daytime temperatures. In rice, reduce grain yield and quality. amplitude daily temperature cycles plants use to set their circadian clock. Therefore, we examined how affect timing molecular activities. field-grown plants, alter pattern transcriptome. Genes with strong rhythmic expression those under control affected...
The vacuolated lens (vl) mouse mutant causes congenital cataracts and neural tube defects (NTDs), with the NTDs being caused by abnormal fold apposition fusion. Our positional cloning of vl indicates these phenotypes result from a deletion mutation in an uncharacterized orphan G protein-coupled receptor (GPCR), Gpr161. Gpr161 displays restricted expression to lateral folds, developing lens, retina, limb, CNS. Characterization that C-terminal tail is truncated, leading multiple effects on...
The circadian clock controls many molecular activities, impacting experimental interpretation. We quantify the genome-wide effects of time-of-day on heat-shock response and "diurnal bias" in stress experiments. Heat has significant adverse plant productivity worldwide. Most experiments examining heat are performed during daytime hours, generating a 'diurnal bias' pathways regulatory mechanisms identified. Such bias may confound downstream interpretations limit our understanding full to...
Sorghum is often exposed to suboptimal low temperature stress under field conditions, particularly at the seedling establishment stage. Enhancing chilling tolerance will facilitate earlier planting and so minimize negative impacts of other stresses experienced later growth stages. Genome-wide association mapping was performed on a sorghum panel grown control (30/20 °C; day/night) (20/10 °C) conditions. Genomic regions chromosome 7, controlling emergence index (root shoot) vigor, were...
Organisms respond to changes in their environment through transcriptional regulatory networks (TRNs). The hierarchy of these can be inferred from expression data. Computational approaches identify TRNs applied any species where quality RNA acquired, However, ChIP-Seq and similar validation methods are challenging employ non-model species. Improving the accuracy computational inference significantly reduce cost time subsequent experiments. We have developed ExRANGES, an approach that improves...
The vacuolated lens (vl) mouse mutant arose spontaneously on the C3H/HeSn background and exhibits neural tube defects (NTDs), congenital cataract, occasionally a white belly spot. We previously reported that 1) vl phenotypes are due to mutation in an orphan G protein-coupled receptor (GPCR), Gpr161; 2) penetrance of NTD cataract affected by genetic background, allowing three unlinked quantitative trait loci (QTL) be mapped (modifiers lens, Modvl1-3); 3) phenotype-based bioinformatics...
Summary Geminiviruses are DNA viruses that cause severe crop losses in different parts of the world, and there is a need for genetic sources resistance to help combat them. Arabidopsis has been used as source virus‐resistant genes derive from alterations essential host factors. We virus‐induced gene silencing ( VIGS ) vector derived geminivirus Cabbage leaf curl virus (Ca LC uV) assess natural variation virus–host interactions 190 accessions. Silencing CH ‐42 , encoding protein needed make...
When abruptly exposed to toxic levels of hexavalent uranium, the extremely thermoacidophilic archaeon Metallosphaera prunae, originally isolated from an abandoned uranium mine, ceased grow, and concomitantly exhibited heightened cytosolic ribonuclease activity that corresponded substantial degradation cellular RNA. The M. prunae transcriptome during 'uranium-shock' implicated VapC toxins as possible causative agents observed RNA degradation. Identifiable PIN-domain proteins encoded in genome...
RNA-seq analysis has enabled the evaluation of transcriptional changes in many species including nonmodel organisms. However, most only a single reference genome is available and reads from highly divergent varieties are typically aligned to this reference. Here, we quantify impacts choice mapping rice where three high-quality genomes available. We data popular productive variety different found that identification differentially expressed genes differed depending on which was used for...
ABSTRACT In rice, a small increase in nighttime temperatures reduces grain yield and quality. How warm ( WNT ) produce these detrimental effects is not well understood, especially field conditions where the normal day to night temperature fluctuation exceeds mild temperature. We observed genome-wide disruption of gene expression timing during reproductive phase on field-grown rice panicles acclimated 2-3°C WNT. Rhythmically expressed transcripts were more sensitive than non-rhythmic...
In many plant species, the time of day at which flowers open to permit pollination is tightly regulated. Proper flower opening, or Time Day Anther Appearance (TAA), may coordinate flowering opening with pollinator activity shift temperature sensitive developmental processes cooler times day. The genetic mechanisms that regulate timing this process in cereal crops are unknown. To address knowledge gap, it necessary establish a monocot model system exhibits variation TAA. Here, we examine...
ABSTRACT Callus and cell suspension culture techniques are valuable tools in plant biotechnology widely used fundamental applied research. For studies callus cultures to be relevant, it is essential know if the underlying biochemistry similar intact plants. This study examined expression of core circadian genes Arabidopsis from named AT2 found that rhythms were impaired. The waveforms like plants light/dark cycles, but became weaker free‐running, constant light conditions. Temperature cycles...
Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting skipping Based on Protein amino acid SequenceS), to assess criticality exon inclusion based solely information contained sequence upstream downstream junctions. By focusing sequence, predicts independent tissue species absence any intronic information. We validate model predictions using...
Gabriela Vazquez Benitez1, Jay Desai1, Emily Schroeder2, Gregory Nichols3, Jodi Segal4, Andy Karter5, John Steiner2, Katherine Newton6, Leo Morales6, Ram Pathak7 and Patrick O’Connor1 1HealthPartners 2Kaiser Permanente Colorado 3Kaiser Northwest 4Johns Hopkins University 5Kaiser Northern California 6Group Health Research Institute 7Marshfield Clinic Foundation
Patrick O’Connor1, Jay Desai1, JoAnn Sperl-Hillen1, Renuka Adibhatla1, Mary Becker1, Kris Ohnsorg1 and Gabriela Vazquez Benitez1 1HealthPartners