A5023542431- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Retinal Diseases and Treatments
- Ferroptosis and cancer prognosis
- Adipose Tissue and Metabolism
- Retinal Development and Disorders
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- Mitochondrial Function and Pathology
- Molecular Biology Techniques and Applications
- Nuclear Receptors and Signaling
- Genetics and Neurodevelopmental Disorders
- Alzheimer's disease research and treatments
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Muscle Physiology and Disorders
- Advanced Proteomics Techniques and Applications
- Genetics, Aging, and Longevity in Model Organisms
Oklahoma Medical Research Foundation
2019-2025
Oklahoma City VA Medical Center
2018-2025
University of Oklahoma Health Sciences Center
2015-2024
Veterans Health Administration
2019-2024
Oklahoma Foundation for Digestive Research
2023
Human Gene Therapy Research Institute
2022
Oklahoma State University Oklahoma City
2020
OU Health Stephenson Cancer Center
2020
Center for Neurosciences
2019
Star Center
2017-2019
Diabetic retinopathy remains a frightening prospect to patients and frustrates physicians. Destruction of damaged retina by photocoagulation the primary treatment nearly 50 years after its introduction. The diabetes pandemic requires new approaches understand pathophysiology improve detection, prevention, retinopathy. This perspective considers how unique anatomy physiology may predispose it metabolic stresses diabetes. roles neural retinal alterations impaired insulin action in pathogenesis...
Abstract Ovarian aging leads to diminished fertility, dysregulated endocrine signaling and increased chronic disease burden. These effects begin emerge long before follicular exhaustion. Female humans experience a sharp decline in fertility around 35 years of age, which corresponds declines oocyte quality. Despite growing body work, the field lacks comprehensive cellular map transcriptomic changes mouse ovary identify early drivers ovarian decline. To fill this gap we performed single-cell...
<b>Background:</b> Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges respect to diagnosis and monitoring of progression. <b>Objectives:</b> To identify biomarker panel elucidates ALS pathogenesis, distinguishes patients from neurologic controls, correlates characteristics, determine the effect <i>HFE</i> gene variants, potential risk factor for sporadic ALS, on profile. <b>Methods:</b> We obtained CSF samples by...
The necessity of including both males and females in molecular neuroscience research is now well understood. However, there relatively limited basic biological data on brain sex differences across the lifespan despite age-related neurological dysfunction disease between females. Whole genome gene expression young (3 months), adult (12 old (24 months) male female C57BL6 mice hippocampus was analyzed. Subsequent bioinformatic analyses confirmations changes hippocampal protein were performed....
The growing interest in the role of epigenetic modifications human health and disease has led to development next-generation sequencing methods for whole genome analysis DNA methylation patterns. However, many projects require targeted specific genes or genomic regions. We have developed an approach, termed BiSulfite Amplicon Sequencing (BSAS), hypothesis driven focused absolute analysis. This approach is applicable both studies as well confirmation genome-wide studies.BSAS uses PCR...
J. Neurochem. (2010) 113 , 1577–1588. Abstract Decreased cognitive performance reduces independence and quality of life for aging individuals. Healthy brain does not involve significant neuronal loss, but little is known about the effects at synaptic terminals. Age‐related decline likely reflects manifestation dysregulated function ineffective neurotransmission. In this study, hippocampal synaptosomes were enriched from young‐adult (3 months), adult (12 aged (26 months) Fischer 344 × Brown...
A decline in mitochondrial function and biogenesis as well increased reactive oxygen species (ROS) are important determinants of aging. With advancing age, there is a concomitant reduction circulating levels insulin-like growth factor-1 (IGF-1) that closely associated with neuronal aging neurodegeneration. In this study, we investigated the effect IGF-1 signaling age on astrocyte metabolism its association learning memory.Learning memory was assessed using radial arm water maze young old...
Abstract Background Age-related cognitive dysfunction, including impairment of hippocampus-dependent spatial learning and memory, affects approximately half the aged population. Induction a variety neuroinflammatory measures has been reported with brain aging but relationship between neuroinflammation decline non-neurodegenerative, normative remains largely unexplored. This study sought to comprehensively investigate expression MHC II immune response pathway glial activation in hippocampus...
Insulin-like growth factor-1 (IGF-1) is an important anabolic hormone that decreases with age. In the past two decades extensive research has determined reduction in IGF-1 component of age-related decline cognitive function multiple species including humans. Deficiency circulating results impairment processing speed and deficiencies both spatial working memory. Replacement or factors increase to old animals humans reverses many these deficits. Despite overwhelming evidence for as...
There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate in aging associated with a heightened state systemic inflammation, which exacerbates blood-brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis synergistic inflammatory processes exert hippocampal function, young aged C57BL/6 mice were rendered obese by chronic feeding high-fat diet followed assessment...
Abstract The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued the could be important factor aging, resulting relaxation gene expression regulation abnormal expression. Since was initially observed decreased age 1974, 16 articles have published describing effect on various tissues from rodents humans. We critically reviewed publications enzymes involved to evaluate validity aging. On basis current...
Modern molecular and biochemical neuroscience studies require analysis of specific cellular populations derived from brain tissue samples to disambiguate cell type-specific events. This is particularly true in the minority glial brain, such as microglia, which may be obscured whole analyses. Microglia have central functions development, aging, neurodegeneration are a current focus research. A long-standing concern for biologists using
Abstract Background Microglia, the brain’s principal immune cells, have been implicated in pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences microglial function and transcriptomic programming described across development models AD, no studies comprehensively identified divergences that emerge aging mouse hippocampus. Further, existing AD generally develop pathology (amyloid plaques tau tangles) early life fail recapitulate...
Abstract Microglia, the brain’s resident macrophages, maintain brain homeostasis and respond to injury infection. During aging they undergo functional changes, but underlying mechanisms their contributions neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia sex dimorphic, so we compared microglial in mice of both sexes. RNA-sequencing hippocampal revealed more aging-associated changes female than male microglia, differences old young microglia....
Abstract Background Despite advances in the understanding of diabetic retinopathy, nature and time course molecular changes retina with diabetes are incompletely described. This study characterized functional phenotype increasing durations diabetes. Results Using streptozotocin-induced rat model diabetes, levels retinal permeability, caspase activity, gene expression were examined after 1 3 months Gene identified by whole genome microarray confirmed qPCR same set animals as used analyses...
Diabetic retinopathy can result in vision loss and involves progressive neurovascular degeneration of the retina. This study tested hypothesis that diabetes decreases retinal expression presynaptic proteins involved synaptic function. The protein mRNA contents for synapsin I, synaptophysin, vesicle-associated membrane 2, synaptosomal-associated 25 kDa postsynaptic density 95 were measured by immunohistochemistry, immunoblotting real-time quantitative polymerase chain reaction whole retinas...
The role of epigenetic processes in the control gene expression has been known for a number years. DNA methylation at cytosine residues is particular interest studies as it demonstrated to be both long lasting and dynamic regulator expression. Efforts examine changes health disease have hindered by lack high-throughput, quantitatively accurate methods. With advent popularization next-generation sequencing (NGS) technologies, these tools are now being applied epigenomics addition existing...