A5073661790- Liver Disease Diagnosis and Treatment
- Cholesterol and Lipid Metabolism
- Porphyrin Metabolism and Disorders
- Adipose Tissue and Metabolism
- Heme Oxygenase-1 and Carbon Monoxide
- Peroxisome Proliferator-Activated Receptors
- Folate and B Vitamins Research
- Liver physiology and pathology
- Air Quality and Health Impacts
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Cancer, Lipids, and Metabolism
- Drug Transport and Resistance Mechanisms
- Pancreatic function and diabetes
- Lipid metabolism and disorders
- Gastrointestinal disorders and treatments
- Metabolism, Diabetes, and Cancer
- Cancer-related gene regulation
- Genetic factors in colorectal cancer
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic Associations and Epidemiology
- Neonatal Health and Biochemistry
- Lipid metabolism and biosynthesis
- Diet, Metabolism, and Disease
- Microscopic Colitis
University of California, Los Angeles
2012-2024
Los Angeles Medical Center
2022-2023
Olive View-UCLA Medical Center
2020-2022
UCLA Health
2015-2018
Howard Hughes Medical Institute
2006-2016
Centre For Digestive Diseases
2014
Icahn School of Medicine at Mount Sinai
2006
Cedars-Sinai Medical Center
2004
Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male female gonadal hormones. Here, we report that the number X chromosomes within cells also contributes these sex differences. We employed a unique mouse model, known as “four core genotypes,” distinguish between (testes or ovaries) (XX XY). With this produced mice carrying XX XY chromosome complements. Mice were gonadectomized remove acute hormones uncover...
Impaired estrogen action is associated with the metabolic syndrome in humans. We sought to determine whether impaired female C57Bl6 mice, produced by whole body Esr1 ablation, could recapitulate aspects of this syndrome, including inflammation, insulin resistance, and obesity. Indeed, we found that global knockout (KO) receptor (ER)α leads reduced oxygen uptake caloric expenditure compared wild-type (WT) mice. In addition, fasting insulin, leptin, PAI-1 levels were markedly elevated, whereas...
Impaired estrogen receptor α (ERα) action promotes obesity and metabolic dysfunction in humans mice; however, the mechanisms underlying these phenotypes remain unknown. Considering that skeletal muscle is a primary tissue responsible for glucose disposal oxidative metabolism, we established reduced ERα expression associated with intolerance adiposity women female mice. To test this relationship, generated muscle-specific knockout (MERKO) homeostasis increased were paralleled by diminished...
The most abundant immune cell type is the neutrophil, a key first responder after pathogen invasion. Neutrophil numbers in periphery are tightly regulated to prevent opportunistic infections and aberrant inflammation. In healthy individuals, more than 1 × 109 neutrophils per kilogram body weight released from bone marrow every 24 hours. To maintain homeostatic levels, an equivalent number of senescent cells must be cleared circulation. Recent studies indicate that clearance by resident...
The hepatitis C virus (HCV) infects more than 180 million people worldwide, with long-term consequences including liver failure and hepatocellular carcinoma. Quercetin bioflavonoids can decrease HCV production in tissue culture, part through inhibition of heat shock proteins. If quercetin demonstrates safety antiviral activity patients, then it could be developed into an inexpensive treatment for third world countries or other affected populations that lack financial means to cover the cost...
We report the genetic analysis of a “humanized” hyperlipidemic mouse model for progressive nonalcoholic steatohepatitis (NASH) and fibrosis. Mice carrying transgenes human apolipoprotein E*3‐Leiden cholesteryl ester transfer protein fed “Western” diet were studied on backgrounds over 100 inbred strains. The mice developed hepatic inflammation fibrosis that was highly dependent background, with vast differences in degree Histological showed features characteristic NASH, including...
Objective: Air pollution is associated with increased cardiovascular morbidity and mortality, as well dyslipidemia metabolic syndrome. Our goal was to dissect the mechanisms involved. Approach Results: We assessed effects of exposure air on lipid metabolism in mice through assessment plasma lipids lipoproteins, oxidized fatty acids 9-HODE (9-hydroxyoctadecadienoic) 13-HODE (13-hydroxyoctadecadienoic), lipid, carbohydrate metabolism. Findings were corroborated, further HepG2 hepatocytes...
Levy, Cynthia; Dickey, Amy K.; Wang, Bruce; Thapar, Manish; Naik, Hetanshi; Keel, Siobán B.; Saberi, Behnam; Beaven, Simon W.; Rudnick, Sean R.; Elmariah, Sarina Erwin, Angelika L.; Goddu, Robert J.; Hedstrom, Karli; Leaf, Rebecca Karp; Kazamel, Mohamed; Mazepa, Marshall; Philpotts, Lisa Liang; Quigley, John; Raef, Haya; Ungar, Jonathan; Anderson, Karl E.; Balwani, Manisha; on behalf of the Porphyrias Consortium Rare Diseases Clinical Network. Author Information
Purpose of review Inflammatory bowel disease is characterized by chronic intestinal inflammation in the absence a recognized pathogen. In its classic description, there are two principal forms inflammatory disease: Crohn and ulcerative colitis. The clinical heterogeneity these disorders alludes to possibility diverse pathogenetic mechanisms underlying diseases. purpose this summarize latest information on biomarkers Recent findings authors have focused serologic markers for which emerging...
The liver X receptors (LXRs) function as nutritional sensors for cholesterol and have important roles in lipid metabolism, glucose homeostasis, inflammation. We provide the first evidence that LXRs are phosphorylated proteins. Mutational analysis metabolic labeling indicate LXRα is on serine 198 hinge region. This a consensus target MAPK family. A phosphorylation‐deficient mutant, S198A, remains nuclear responds to ligands like wild‐type protein. biological significance of LXR...
Liver X receptors (LXRs) are determinants of hepatic stellate cell (HSC) activation and liver fibrosis. Freshly isolated HSCs from Lxr αβ −/− mice have increased lipid droplet (LD) size, but the functional consequences this unknown. Our aim was to determine whether LXRs link cholesterol retinoid storage in how impacts activation. Primary wild‐type were profiled by gene array during vitro Lipid content quantified high‐performance liquid chromatography mass spectroscopy. treated with nuclear...
Background & AimsLiver fibrosis is a multifactorial trait that develops in response to chronic liver injury. Our aim was characterize the genetic architecture of carbon tetrachloride (CCl4)-induced using Hybrid Mouse Diversity Panel, panel more than 100 genetically distinct mouse strains optimized for genome-wide association studies and systems genetics.MethodsChronic injury induced by CCl4 injections twice weekly 6 weeks. Four hundred thirty-seven mice received 256 vehicle, after which...
Significance The saccharide ribose is naturally present in food and circulates the blood. Previous studies suggest that cells internalize directly from extracellular space, but how, why, where this occurs body are not well understood. Here, we developed a new PET probe to monitor process vivo. Using [ 14 C]ribose, show salvage concentrated liver. We identify solute carrier family 2, member 2 one of potentially several transporters. demonstrate down-regulated during metabolic syndrome. This...
Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics. We aimed to identify noninvasive independent endoscopic retrograde cholangiopancreatography (ERCP)-confirmed and accordingly developed predictive machine learning models (MLMs).Clinical data consecutive patients undergoing first-ever ERCP for suspected from 2015-2019 were abstracted a prospectively-maintained database. Multiple logistic regression was used ERCP-confirmed...
Krüppel-like factor 6 (KLF6) is a cancer gene (). Here, we demonstrate that KLF6 protein rapidly degraded when apoptosis induced via the intrinsic pathway by cisplatin, adriamycin, or UVB irradiation in multiple cell lines (HCT116, SW40, HepG2, PC3-M, Skov3, NIH-3T3, 293T, GM09706, and MEF, IMR-90). degradation occurred presence absence of p53, was associated with ubiquitination, mediated proteasome (half-life 16min, unstimulated), independent caspases calpain. unchanged...
Abstract Background Acute hepatic porphyria (AHP) is a group of rare but treatable conditions associated with diagnostic delays 15 years on average. The advent electronic health records (EHR) data and machine learning (ML) may improve the timely recognition diseases like AHP. However, prediction models can be difficult to train given limited case numbers, unstructured EHR data, selection biases intrinsic healthcare delivery. We sought characterize for identifying patients Methods This study...