A5011471240- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Adipose Tissue and Metabolism
- PI3K/AKT/mTOR signaling in cancer
- Neuropeptides and Animal Physiology
- Protein Kinase Regulation and GTPase Signaling
- Treatment of Major Depression
- Cholesterol and Lipid Metabolism
- Stress Responses and Cortisol
- Adipokines, Inflammation, and Metabolic Diseases
- Sleep and Wakefulness Research
- Metabolism, Diabetes, and Cancer
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neuropharmacology Research
- Anesthesia and Neurotoxicity Research
- Cancer, Hypoxia, and Metabolism
- Smoking Behavior and Cessation
- Genomics and Chromatin Dynamics
- Aquaculture Nutrition and Growth
- Peroxisome Proliferator-Activated Receptors
- Dietary Effects on Health
- Primate Behavior and Ecology
- Advanced Power Generation Technologies
- Cellular Mechanics and Interactions
- Muscle Physiology and Disorders
University of Cincinnati
2004-2017
University of Cincinnati Medical Center
1998-2013
Information Technology University
2013
City of Hope
2012
Beckman Research Institute
2012
Cincinnati Children's Hospital Medical Center
2012
City Of Hope National Medical Center
2012
Veterans Health Administration
1997-1999
Significance Cancer cells reprogram their metabolism for optimal growth and survival. AMPK-activated protein kinase (AMPK) is a key energy sensor that controls many metabolic pathways including reprogramming. However, its role in cancer poorly understood. Some studies claim it has tumor suppressor while others show protumor role. Two AMPK-activating compounds (including metformin, now clinical trials) are widely used to suppress cell proliferation. We found AMPK abundantly expressed...
The G-protein–mediated Rho guanine nucleotide exchange factor (GEF)–Rho GTPase signaling axis has been implicated in human pathophysiology and is a potential therapeutic target. By virtual screening of chemicals that fit into surface groove the DH-PH domain LARG, G-protein–regulated GEF involved RhoA activation, subsequent validations biochemical assays, we have identified class chemical inhibitors represented by Y16 are active specifically inhibiting LARG binding to RhoA. binds junction...
Proliferating cell nuclear antigen (PCNA), a potential anticancer target, forms homotrimer and is required for DNA replication numerous other cellular processes. The purpose of this study was to identify novel small molecules that modulate PCNA activity affect tumor proliferation. An in silico screen compound library against crystal structure subsequent structural similarity search the ZINC chemical database were carried out derive relevant docking partners. Nine compounds, termed inhibitors...
Mice respond to fatty acid synthase (FAS) inhibitors by profoundly reducing their food intake and body weight. Evidence indicates that the central nervous system (CNS) may be critical site of action; however, a peripheral contribution cannot ruled out. We compared doses FAS inhibitor C75 in CNS (third ventricle [i3vt]) periphery (intraperitoneal [IP]) reduce weight rats. Centrally, threshold dose was 3 μg, whereas 10 mg/kg required peripherally. Such data argue for activity as potent target...
HIV-1 Nef triggers down-regulation of cell-surface MHC-I by assembling a Src family kinase (SFK)-ZAP-70/Syk-PI3K cascade. Here, we report that chemical disruption the Nef-SFK interaction with small molecule inhibitor 2c blocks assembly multi-kinase complex and represses HIV-1–mediated in primary CD4 + T-cells. did not interfere PACS-2–dependent trafficking required for or AP-1 PACS-1–dependent sequestering internalized MHC-I, suggesting specifically interfered triggering down-regulation....
Abstract ABCG4 is an ATP-binding cassette transmembrane protein which has been shown, in vitro , to participate the cellular efflux of desmosterol and amyloid-β peptide (Aβ). highly expressed brain, but its localization function at blood-brain barrier (BBB) level remain unknown. We demonstrate by qRT-PCR confocal imaging that mouse Abcg4 brain capillary endothelial cells. Modelling studies dimer suggested showed thermodynamically favorable binding putative sterol-binding site, this was...
In general, tropical birds have a "slow pace of life," lower rates whole-animal metabolism and higher survival rates, than temperate species. A fundamental challenge facing physiological ecologists is the understanding how variation in life-history at whole-organism level might be linked to cellular function. Because metabolism, we hypothesized that cells from species would also similar body size common phylogenetic history. We cultured primary dermal fibroblasts 17 phylogenetically-paired...
Removal of adrenal steroids by adrenalectomy (ADX) reduces food intake and body weight in rodents prevents excessive gain many genetic dietary models obesity. Thus, glucocorticoids appear to play a key role promote positive energy balance normal pathological conditions. By comparison, central nervous system melanocortin signaling provides critical inhibitory tone regulate balance. The present experiments sought test whether influence altering the sensitivity receptor ligands. Because...
OBJECTIVE: To screen for dopaminergic abnormalities in tobacco smokers and patients with posttraumatic stress disorder (PTSD), the authors determined serial CSF plasma concentrations of dopamine metabolite homovanillic acid (HVA). METHOD: Continuous subarachnoid sampling was used to obtain 37 samples over 6 hours 13 normal volunteers 11 combat-related PTSD; 10 smoked 14 had never smoked. The were abstinent from 17 hours. RESULTS: markedly lower CSF, but not plasma, HVA levels. Their averaged...
Abstract Leptin (OB protein) is an important signal in the regulation of energy balance. levels correlate with adiposity, but also decrease acutely caloric restriction and increase refeeding. The brain established critical site leptin function, yet little known about concentrations central nervous system relative to plasma levels, psychiatric diagnoses, other endocrine parameters. Therefore, using a novel ultrasensitive assay, we explored relationships human cerebrospinal fluid (CSF) body...
Myostatin, a member of the transforming growth factor (TGF)-β family secreted ligands, is strong negative regulator muscle growth. As such, therapeutic inhibitors myostatin are actively being investigated for their potential in treatment muscle-wasting diseases such as muscular dystrophy and sarcopenia. Here, we sought to develop high-throughput screening (HTS) method small-molecule that target myostatin. We created HEK293 stable cell line expresses (CAGA)12-luciferase reporter construct...
When neuropeptide Y (NPY) is administered centrally, meal-anticipatory responses are elicited. If an increase of endogenous NPY a signal that heralds imminent large caloric load, timed daily injections may be expected to condition facilitate ingestion. Rats received 4-h access food beginning in the morning and then (1600 h), third-ventricular or saline for 7 days. On test day (day 8), animals conditioning drug (NPY saline) opposite drug. Food was available immediately after injection on day,...
Removal of glucocorticoids by adrenalectomy (ADX) reduces food intake and body weight in rodents prevents excessive gain many genetic dietary models obesity. Glucocorticoids play a key role to promote positive energy balance normal pathological conditions, at least part, altering the sensitivity hypothalamic peptides. The hyperphagia after central neuropeptide Y administration, for example, is attenuated ADX, there evidence that influence both MCH orexin A activity. In present study, feeding...