A5079657055- Circadian rhythm and melatonin
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Dermatology and Skin Diseases
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Acute Myeloid Leukemia Research
- Hereditary Neurological Disorders
- Gastrointestinal motility and disorders
- Inflammasome and immune disorders
- PARP inhibition in cancer therapy
- Allergic Rhinitis and Sensitization
- Metabolomics and Mass Spectrometry Studies
- interferon and immune responses
- Genetic Mapping and Diversity in Plants and Animals
- Autophagy in Disease and Therapy
- Light effects on plants
- Forensic and Genetic Research
- Asthma and respiratory diseases
- Sleep and Wakefulness Research
- Immune responses and vaccinations
- Plant Molecular Biology Research
- Genomic variations and chromosomal abnormalities
- Adrenal Hormones and Disorders
- Lymphoma Diagnosis and Treatment
Vanda Pharmaceuticals (United States)
2019-2025
Cleveland Clinic
2007-2024
Case Western Reserve University
2018-2024
Mayo Clinic in Arizona
2024
Royal Holloway University of London
2009-2023
University of Washington
2018
Dr. John T. Macdonald Foundation
2018
University of Miami
2018
New York Hospital Queens
2018
Columbia University
2018
Recent COVID-19 (coronavirus disease 2019) host genetics studies suggest enrichment of mutations in genes involved the regulation type I and III interferon (IFN) immunity patients with severe infection. We performed whole-genome sequencing analysis samples obtained from participating ongoing ODYSSEY phase 3 study hospitalised infection receiving supplemental oxygen support. focused on burden testing categories rare common loss-of-function (LOF) variants all IFN pathway genes, specifically...
Neurokinin receptor 1 antagonists are effective in reducing nausea and vomiting chemotherapy-induced emesis. We investigated the safety efficacy of tradipitant, a neurokinin antagonist, patients with idiopathic diabetic gastroparesis.
Abstract The genetic background of Atopic Dermatitis (AD) with chronic pruritus is complex. Filaggrin ( FLG ) an essential gene in the epidermal barrier formation s. Loss-of-function (LOF) variants associated skin dysfunction constitute most well-known risk factor for AD. In this study, we focused on frequency and effect loss-of-function association self-reported age-of-onset dataset consisted 386 whole-genome sequencing (WGS) samples. We observe a significant between LOF status...
Elevated Interleukin-6 (IL-6) may play an important role in the pathophysiology of COVID-19 yet attenuated response is not seen across all severe patients. We aimed to determine effect IL-6 baseline levels and other clinical variables on mortality outcomes hospitalized patients as well explore genetic variants associated with response.Baseline cytokine were measured participating ongoing ODYSSEY phase 3 randomized study tradipitant placebo who are receiving supplemental oxygen support....
Objective: To determine if iloperidone, a second-generation antipsychotic, reduces symptoms of bipolar mania.Methods: This phase 3, randomized, double-blind, placebo-controlled study was conducted in adults with mania at 27 US and international sites between April 2021 September 2022.Participants were randomized 1:1 to iloperidone (up 24 mg/d given twice daily) or placebo for 4 weeks.The primary efficacy endpoint change from baseline week Young Mania Rating Scale (YMRS) total score versus...
Immunoglobulin mu-binding protein 2 (IGHMBP2) pathogenic variants lead to a spectrum of disorders characterized by alpha-motor neuron degeneration. We describe compound heterozygous patient diagnosed with Charcot-Marie-Tooth disease type 2S in IGHMBP2: missense variant acting trans confirmed intronic cryptic splice site variant. This was shown result the creation new acceptor site, loss reading frame and nonsense-mediated decay. designed 19-mer antisense oligonucleotide targeting this...
Genome-wide association studies have recently identified 3p21.31, with lead variant pointing to the CXCR6 gene, as strongest thus far reported susceptibility risk locus for severe manifestation of COVID-19. In order determine its role, we measured plasma levels Chemokine (C-X-C motif) ligand 16 (CXCL16) in COVID-19 hospitalized patients. CXCL16 interacts promoting chemotaxis or cell adhesion. The CXCR6/CXCL16 axis mediates homing T cells lungs disease and hyper-expression is associated...
The heterogeneity of the whole-exome sequencing (WES) data generation methods present a challenge to joint analysis. Here we bioinformatics strategy for joint-calling 20,504 WES samples collected across nine studies and sequenced using ten capture kits in fourteen centers Alzheimer's Disease Sequencing Project. joint-genotype called variant-called format (VCF) file contains only positions within union kits. VCF was then processed specifically account batch effects arising from use different...
<h3>Objective</h3> To identify genetic variation influencing late-onset Alzheimer disease (LOAD), we used a large data set of non-Hispanic white (NHW) extended families multiply-affected by LOAD performing whole genome sequencing (WGS). <h3>Methods</h3> As part the Disease Sequencing Project, WGS were generated for 197 NHW participants from 42 (affected individuals and unaffected, elderly relatives). A two-pronged approach was taken. First, variants prioritized using heterogeneity logarithm...
Abstract SARS-coronavirus 2 is the causal agent of COVID-19 outbreak. SARS-Cov-2 entry into a cell dependent upon binding viral spike (S) protein to cellular receptor and on cleavage by host proteases such as Cathepsin L B. CTSL/B are crucial elements lysosomal pathway both enzymes almost exclusively located in lysosomes.CTSL disruption offers potential for CoVID-19 therapies. The mechanisms include: decreasing expression CTSL, direct inhibition CTSL activity affecting conditions environment...
Abstract Recurrent waves of SARS CoV2 infections remain a major global health concern. Emergence highly infectious variants with reduced sensitivity to neutralization by vaccines and monoclonal antibodies (mAb) necessitates deeper understanding factors involved in identification drug candidates halt infection. Here, we determined the primacy endosomal protease cathepsin-L mediating entry screened library well-annotated bioactive compounds for potent inhibitory activity. Whilst inhibitors...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels generate electrical rhythmicity in various tissues although primarily heart, retina and brain. The HCN channel blocker compound, Ivabradine (Corlanor), is approved by the US Food Drug Administration (FDA) as a medication to lower heart rate blocking hyperpolarization activated inward current sinoatrial node. In addition, growing body of evidence suggests role for regulation sleep/wake behavior. Zebrafish larvae are ideal...
Effective approaches for assessing mitochondrial DNA (mtDNA) variation are important to multiple scientific disciplines. Mitochondrial haplogroups characterize branch points in the phylogeny of mtDNA. Several tools exist haplogroup classification. However, most require full or partial mtDNA sequence which is often cost prohibitive studies with large sample sizes. The purpose this study was develop Hi-MC, a high-throughput method classification that effective and applicable sizes making...
Animals are used as preclinical models for human diseases in drug development. Dogs, especially, research to support clinical safety evaluations during Comparisons of patterns regions homozygosity (ROH) and phenotypes between dogs humans not well known. We conducted a genome-wide analysis (GWHA) on the dog genomes. calculated ROH across distinct cohorts, including Amish, 1000 genomes, Vanda 1 k Alzheimer’s cohort. The Amish provided large cohort extended kinships, allowing in-depth...
Gastroparesis is a serious medical condition characterized by delayed gastric emptying and symptoms of nausea, vomiting, bloating, fullness after meals, abdominal pain.To ascertain the genetic risk factors for gastroparesis, we conducted largest thus far whole-genome sequencing study gastroparesis. We investigated frequency effect rare loss-of-function variants in patients with both idiopathic diabetic gastroparesis enrolled clinical gastroparesis.Among variants, reported an increased...
Sweet basil is a popular culinary herb used in many cuisines around the world and widely grown commercially for retail as live potted plant. However, easily damaged by temperatures below 12 °C meaning plants must be transported from grower to retailer warm transport chain, adding considerable commercial cost temperate countries. Improvement of chilling tolerance has been demonstrated post-harvest crops such tomato fruits and, indeed, fresh cut basil, manipulation red:far red ratio light...
HIV-associated neurocognitive impairment (NCI) is a term established to capture wide spectrum of HIV related deficits ranging in severity from asymptomatic dementia. The genetic underpinnings this complex phenotype are incompletely understood. Mitochondrial function has long been thought play role neurodegeneration, along with iron metabolism and transport. In work, we aimed characterize the interplay mitochondrial DNA (mtDNA) haplogroup nuclear associations NCI phenotypes CHARTER cohort,...
We aimed to test the proposal that progressive combinations of multiple promoter elements acting in concert may be responsible for full range phases observed plant circadian output genes. In order allow reliable selection informative phase groupings genes our purpose, intrinsic cyclic patterns expression were identified using a novel, non-biased method identification Our approach two dominant, inherent orthogonal trends underlying publicly available microarray data from plants maintained...