A5037436368- Liver Disease Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Ferroptosis and cancer prognosis
- Epigenetics and DNA Methylation
- Systemic Lupus Erythematosus Research
- Bioinformatics and Genomic Networks
- Cardiac Arrhythmias and Treatments
- Ubiquitin and proteasome pathways
- Folate and B Vitamins Research
- Rheumatoid Arthritis Research and Therapies
- Cancer, Lipids, and Metabolism
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Atrial Fibrillation Management and Outcomes
- Neonatal Respiratory Health Research
- Cytokine Signaling Pathways and Interactions
- Adipose Tissue and Metabolism
- Extracellular vesicles in disease
- Metabolism and Genetic Disorders
- Salivary Gland Disorders and Functions
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
Oklahoma Medical Research Foundation
2016-2025
Human Gene Therapy Research Institute
2022-2023
Oklahoma Foundation for Digestive Research
2023
University of Oklahoma Health Sciences Center
2017-2022
Florida International University
2022
Florida Atlantic University
2022
Auburn University
2022
University of South Alabama
2022
USA Mitchell Cancer Institute
2022
Mayo Clinic in Florida
2011-2012
A common challenge in the analysis of genomics data is trying to understand underlying phenomenon context all complex interactions taking place on various signaling pathways. statistical approach using models universally used identify most relevant pathways a given experiment. Here, we show that existing pathway methods fail take into consideration important biological aspects and may provide incorrect results certain situations. By systems biology approach, developed an impact includes...
Summary Gene expression is dynamically regulated in a variety of mammalian physiologies. During aging, there are changes that occur protein highly controlled by the regulatory steps transcription, post‐transcription, and post‐translation. Although global profiles human transcripts during aging processes available, mechanism(s) which differentially expressed between young old cohorts remains unclear. Here, we report on N6‐methyladenosine (m6A) RNA modification peripheral blood mononuclear...
Summary DNA methylation is a central regulator of genome function, and altered patterns are indicative biological aging mortality. Age‐related cellular, biochemical, molecular changes in the hippocampus lead to cognitive impairments greater vulnerability neurodegenerative disease that varies between sexes. The role hippocampal epigenomic with these processes unknown as no genome‐wide analyses age‐related have considered factor sex controlled animal model. High‐depth, bisulfite sequencing...
In dividing cells, DNA replication occurs in a precise order, but many questions remain regarding the mechanisms of timing establishment and regulation. We now have generated genome-wide, high-resolution maps throughout zebrafish development. Unexpectedly, rapid cell cycles preceding midblastula transition, defined program was present that predicted initial wave zygotic transcription. Replication thereafter progressively continuously remodeled across majority genome, epigenetic changes...
Epigenetic alterations are a hallmark of aging and age-related diseases. Computational models using DNA methylation data can create "epigenetic clocks" which proposed to reflect "biological" aging. Thus, it is important understand the relationship between predictive clock sites biology. To do this, we examined over 450,000 from 9,699 samples. We found ~20% measured genomic cytosines be used make many different epigenetic clocks whose age prediction performance surpasses that telomere length....
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in United States and primarily caused by cigarette smoking. Increased numbers mucus-producing secretory ("goblet") cells, defined as goblet cell metaplasia or hyperplasia (GCMH), contributes significantly to COPD pathophysiology. The objective this study was determine whether NOTCH signaling regulates differentiation response smoke. Primary human bronchial epithelial cells (HBECs) from nonsmokers smokers with...
Sepsis remains a leading cause of death for humans and currently has no pathogenesis-specific therapy. Hampered progress is partly due to lack insight into deep mechanistic processes. In the past decade, deciphering functions small noncoding miRNAs in sepsis pathogenesis became dynamic research topic. To screen new miRNA targets therapeutics, we used samples array analysis PBMCs from patients with control individuals, blood 2 cohorts sepsis, multiple animal models: mouse cecum ligation...
Abstract Nonalcoholic fatty liver disease (NAFLD) is one of the etiologies that contribute to hepatocellular carcinoma (HCC), and chronic inflammation proposed mediators HCC. Because necroptosis a cell death pathway induces inflammation, we tested whether necroptosis-induced contributes progression NAFLD HCC in mouse model diet-induced Male female wild-type (WT) mice models where blocked (Ripk3−/− or Mlkl−/− mice) were fed either control diet, choline-deficient low-fat diet high-fat diet....
Onto-Tools is a freely available web-accessible software suite, composed of an annotation database and nine complementary data-mining tools. This article describes new tool, Onto-Express-to-go (OE2GO), as well some features implemented in Pathway-Express Onto-Miner over the past year. (PE) has been enhanced to identify significantly perturbed pathways given condition using differentially expressed genes input. OE2GO tool for functional profiling custom annotations. The development this was...
Choice of a T lymphoid fate by hematopoietic progenitor cells depends on sustained Notch–Delta signaling combined with tightly regulated activities multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis gene expression trajectories from beginning to end specification, tests short-term Notch dependence these changes, and analyses effects overexpression two essential factors, namely PU.1 GATA-3....
Proteins involved in endocytosis promote the internalization and degradation of VEGFR3, ensuring valve formation lymphatic vessels.
Current models propose that group 2 innate lymphoid cells (ILC2s) are generated in the bone marrow. Here, we demonstrate subsets of these can differentiate from multipotent progenitors and committed T cell precursors thymus, both vivo vitro. These thymic ILC2s exit circulate blood, home to peripheral tissues. Ablation E protein transcription factors greatly promotes ILC fate while impairing B development. Consistently, a transcriptional network centered on ZBTB16 factor IL-4 signaling...
Sarcopenia has a significant negative impact on healthspan in the elderly and effective pharmacologic interventions remain elusive. We have previously demonstrated that sarcopenia is associated with reduced activity of sarcoplasmic reticulum Ca2+ ATPase (SERCA) pump. asked whether restoring SERCA using activation aging mice could mitigate phenotype. treated 16-month male C57BL/6J vehicle or CDN1163, an allosteric activator, for 10 months. At 26 months, maximal was 41% gastrocnemius muscle...
Loss of innervation is a key driver age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced with the generation mitochondrial hydroperoxides lipid mediators produced downstream cPLA2 12/15 lipoxygenase (12/15-LOX). To define pathological impact generated in denervation-induced vivo, we treated mice liproxstatin-1, hydroperoxide scavenger. We adult male 5 mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection...
Five to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for demyelinating diseases central nervous system, these treatments can be limiting subsets patients due adverse effects and expense. To circumvent barriers, we investigated a nutritional intervention in mice undergoing experimental encephalomyelitis (EAE), model autoimmune-mediated demyelination that induces visual motor pathologies similar...
Abstract Acute respiratory distress syndrome ( ARDS ) induced by severe sepsis can trigger persistent inflammation and fibrosis. We have shown that experimental in baboons recapitulates progression humans, including chronic long‐lasting fibrosis the lung. Complement activation products may contribute to fibroproliferative response, suggesting complement inhibitors are potential therapeutic agents. been suggested treatment of septic with compstatin, a C3 convertase inhibitor protects against...
Lipids are essential components of the nervous system. However, functions very long-chain fatty acids (VLC-FA; ≥ 28 carbons) in brain unknown. The enzyme ELOngation Very Long-chain acids-4 (ELOVL4) catalyzes rate-limiting step biosynthesis VLC-FA (Agbaga et al., Proc Natl Acad Sci USA 105(35): 12843–12848, 2008; Logan J Lipid Res 55(4): 698–708, 2014), which we identified as saturated (VLC-SFA). Homozygous mutations ELOVL4 cause severe neuropathology humans (Ozaki JAMA Neurol 72(7): 797–805,...
Mechanisms that preserve and maintain the cellular proteome are associated with long life healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis dealt by cell through regulation antioxidants, protein degradation, repair oxidized amino acids. Methionine sulfoxide reductase A (MsrA) repairs oxidation free- protein-bound methionine residues enzymatic reduction found in both cytosol mitochondria. Previous studies Drosophila have shown increasing expression...
Abstract Defects in neuromuscular innervation contribute significantly to the age-related decline muscle mass and function (sarcopenia). Our previous studies demonstrated that denervation induces mitochondrial hydroperoxide production (H 2 O lipid hydroperoxides (LOOHs)). Here we define relative contribution of electron transport chain (ETC) derived H versus cytosolic phospholipase A (cPLA ) LOOHs neurogenic atrophy. We show increases cPLA protein content, activity, metabolites downstream...
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables that has demonstrated anti-cancer, anti-microbial and anti-oxidant properties. SFN ameliorates various disease models in rodents (e.g., cancer, diabetes, seizures) are likewise mitigated by dietary restrictions leading us to test the hypothesis this compound elicits cellular responses consistent with being a fasting/caloric restriction mimetic. Using immortalized human retinal pigment epithelial cells, we report...