A5066389423- Liver Disease Diagnosis and Treatment
- Alcohol Consumption and Health Effects
- Eicosanoids and Hypertension Pharmacology
- Adipose Tissue and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Carcinogens and Genotoxicity Assessment
- Cancer, Hypoxia, and Metabolism
- Toxic Organic Pollutants Impact
- Liver Disease and Transplantation
- Endoplasmic Reticulum Stress and Disease
- Liver Diseases and Immunity
- Fatty Acid Research and Health
- Lipid metabolism and disorders
- Peroxisome Proliferator-Activated Receptors
- Immune cells in cancer
- Drug-Induced Hepatotoxicity and Protection
- Genomics, phytochemicals, and oxidative stress
- Pharmacogenetics and Drug Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Hepatitis C virus research
- Gut microbiota and health
- Cancer, Lipids, and Metabolism
- Phagocytosis and Immune Regulation
University of Louisville
2016-2025
University of Louisville Hospital
2020-2024
Laboratory of Molecular Genetics
2015
Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. ω-6 PUFAs exert pro-inflammatory activity, while ω-3 promote anti-inflammatory activity that is mediated, part, through specialized pro-resolving mediators [e.g., resolvin D1 (RvD1)]. We tested the hypothesis a decrease ω-6:ω-3 PUFA ratio would attenuate EtOH-mediated gut-liver axis. FA desaturase-1 (fat-1) mice, which endogenously increase levels, were protected against...
Mixed lineage kinase domain-like pseudokinase (MLKL), a key terminal effector of necroptosis, also plays role in intracellular vesicle trafficking that is critical for regulating liver inflammation and injury alcohol-associated disease (ALD). Although receptor interacting protein 3 (Rip3)-/- mice are completely protected from ethanol-induced injury, Mlkl-/- only partially protected. Therefore, we hypothesized cell-specific functions MLKL may contribute to injury.
Polychlorinated biphenyls (PCBs) are environmental pollutants associated with non-alcoholic-steatohepatitis (NASH), diabetes, and obesity. We previously demonstrated that the PCB mixture, Aroclor 1260, induced steatohepatitis activated nuclear receptors in a diet-induced obesity mouse model. This study aims to evaluate interactions pregnane-xenobiotic receptor (Pxr: Nr1i2) constitutive androstane (Car: Nr1i3) NASH. Wild type C57Bl/6 (WT), Pxr−/− Car−/− mice were fed high fat diet (42% milk...
The purpose of this study is to identify an environmentally relevant shared receptor target for endocrine and metabolism disrupting chemical pollutants. A feature the tested chemicals was that they induced Cyp2b10 in vivo implicating activation constitutive androstane (CAR). Recent studies suggest these compounds could be indirect CAR activators via epidermal growth factor (EGFR) inhibition. Assays included a activity reporter assay, EGF endocytosis EGFR phosphorylation assay. Docking...
1. Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that disrupt hepatic xenobiotic and intermediary metabolism, leading to metabolic syndrome nonalcoholic steatohepatitis (NASH). 2. Since phenobarbital indirectly activates Constitutive Androstane Receptor (CAR) by antagonizing growth factor binding the epidermal receptor (EGFR), we hypothesized PCBs may also diminish EGFR signaling. 3. The effects of PCB mixture Aroclor 1260 on protein phosphorylation cascade...
Dioxin-like molecules have been associated with endocrine disruption and liver disease. To better understand aryl hydrocarbon receptor (AHR) biology, metabolic phenotyping proteomics were performed in mice following ligand-activation or whole-body genetic ablation of this receptor. Male wild type (WT) Ahr-/- (Taconic) fed a control diet exposed to 3,3',4,4',5-pentachlorobiphenyl (PCB126) (61 nmol/kg by gavage) vehicle for two weeks. PCB126 increased expression canonical AHR targets (Cyp1a1...
During the coronavirus disease 2019 (COVID-19) pandemic, there was a marked increase in alcohol consumption. COVID-19 superimposed on underlying liver notably worsens outcome of many forms injury. The goal current pilot study to test dual exposure and infection an experimental animal model alcohol-associated (ALD).
Background: The evolution of “omic” technologies, which measure all biological molecules a specific type (e.g., genomics), has enabled rapid and cost-effective data acquisition, depending on the technique sample size. This, however, generates new hurdles that need to be addressed should improved upon. This includes selecting appropriate statistical test based study design in high-throughput manner. Methods: An automated analysis pipeline for omic datasets we coined STATom@ic (pronounced...
Alcoholic liver disease (ALD) comprises a spectrum of pathology, including steatosis, steatohepatitis, and cirrhosis. Previous work from our group others suggests that dietary fat, both the amount composition, plays pivotal role in ALD development progression; however, impact specific fatty acids on pathogenesis is not fully elucidated. Preclinical rodent models revealed deleterious effects omega-6 polyunsaturated (n-6 PUFAs), specifically linoleic acid (LA), this may be partially attributed...
Alcohol‐associated liver disease (ALD) is a spectrum of disorders ranging from steatosis to steatohepatitis, fibrosis, and cirrhosis. hepatitis (AH) an acute often severe form ALD with substantial morbidity mortality. The mechanisms mediators progression severity are not well understood, effective therapeutic options limited. Various bioactive lipid have recently emerged as important factors in pathogenesis. current study aimed examine alterations linoleic acid (LA)‐derived metabolites the...
Alcohol-associated liver disease (ALD) is a prevalent disorder and significant global healthcare burden with limited effective therapeutic options. The gut-liver axis critical factor contributing to susceptibility injury due alcohol consumption. In the current study, we tested whether human beta defensin-2 (hBD-2), small anti-microbial peptide, attenuates experimental chronic ALD. Male C57Bl/6J mice were fed an ethanol (EtOH)-containing diet for 6 weeks daily administration of hBD-2 (1.2...
Background: Alcohol-associated hepatitis (AH) is one of the clinical presentations alcohol-associated liver disease. AH has poor prognosis, and corticosteroids remain mainstay drug therapy. However, ~40% patients do not respond to this treatment, mechanisms underlying altered response are understood. The current study aimed identify changes in hepatic protein expression associated with responsiveness prognosis AH. Methods: Patients were enrolled based on National Institute Alcohol Abuse...
Environmental pollution contributes to fatty liver disease pathogenesis. Polychlorinated biphenyl (PCB) exposures have been associated with enzyme elevation and suspected steatohepatitis in cohort studies. Male mice treated the commercial PCB mixture, Aroclor 1260 (20 mg/kg), fed high fat diet (HFD) for 12 weeks developed steatohepatitis. Receptor-based modes of action including inhibition epidermal growth factor (EGF) receptor were previously proposed, but other mechanisms likely exist....
Alcohol-associated liver disease (ALD) is a major human health issue for which there are limited treatment options. Experimental evidence suggests that nutrition plays an important role in ALD pathogenesis, and specific dietary fatty acids, example, n6 or n3-PUFAs, may exacerbate attenuate ALD, respectively. The purpose of the current study was to determine whether beneficial effects n3-PUFA enrichment were mediated, part, by improvement Wnt signaling. Wild-type (WT) fat-1 transgenic mice...
Alcohol-associated liver disease (ALD) is a major health problem with limited effective treatment options. hepatitis (AH) subset of severe ALD high rate mortality due to infection, inflammation, and ultimately multi-organ failure. There an urgent need for novel therapeutic approaches alleviate the human suffering associated this condition. Resolvin D1 (RvD1) promotes resolution inflammation regulates immune responses. The current study aimed test efficacy mechanisms RvD1-mediated effects on...