A5085846525- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Immune cells in cancer
- Metabolomics and Mass Spectrometry Studies
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Cytomegalovirus and herpesvirus research
- Biochemical and Molecular Research
- Metabolism and Genetic Disorders
- Amino Acid Enzymes and Metabolism
- Biosimilars and Bioanalytical Methods
- Redox biology and oxidative stress
- Genomics, phytochemicals, and oxidative stress
- Pancreatic function and diabetes
- Adenosine and Purinergic Signaling
- Odor and Emission Control Technologies
- CAR-T cell therapy research
- RNA modifications and cancer
- Selenium in Biological Systems
- Heavy metals in environment
- Glycogen Storage Diseases and Myoclonus
- Kruppel-like factors research
- Mass Spectrometry Techniques and Applications
- Oral Health Pathology and Treatment
- Mercury impact and mitigation studies
University of Kentucky
2018-2024
Markey Cancer Center
2018-2024
The Ohio State University
2020
University of Louisville
2012
University of California, Davis
2004-2005
Abstract Profound metabolic changes are characteristic of macrophages during classical activation and have been implicated in this phenotype. Here we demonstrate that nitric oxide (NO) produced by murine is responsible for TCA cycle alterations citrate accumulation associated with polarization. 13 C tracing mitochondrial respiration experiments map NO-mediated suppression metabolism to aconitase (ACO2). Moreover, find inflammatory reroute pyruvate away from dehydrogenase (PDH) an...
T cells undergo metabolic rewiring to meet their bioenergetic, biosynthetic and redox demands following antigen stimulation. To fulfil these needs, effector must adapt fluctuations in environmental nutrient levels at sites of infection inflammation. Here, we show that can utilize inosine, as an alternative substrate, support cell growth function the absence glucose vitro. metabolize inosine into hypoxanthine phosphorylated ribose by purine nucleoside phosphorylase. We demonstrate subunit...
Upon antigen stimulation, T lymphocytes undergo dramatic changes in metabolism to fulfill the bioenergetic, biosynthetic and redox demands of proliferation differentiation. Glutathione (GSH) plays an essential role controlling balance cell fate. While GSH can be recycled from disulfide (GSSG), inhibition this recycling pathway does not impact content murine By contrast, de novo synthesis GSH, by deleting either catalytic (Gclc) or modifier (Gclm) subunit glutamate-cysteine ligase (Gcl),...
Robust and effective T cell immune surveillance cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth cytokine production. Here, we show that asparagine (Asn) restriction on CD8
Effective T cell-mediated immune responses require the proper allocation of metabolic resources to sustain growth, proliferation, and cytokine production. Epigenetic control genome also governs cell transcriptome lineage commitment maintenance. Cellular programs interact with epigenetic regulation by providing substrates for covalent modifications chromatin. By using complementary genetic, epigenetic, approaches, we revealed that tricarboxylic acid (TCA) cycle flux fueled biosynthetic...
Conventional two-dimensional (2D) cell cultures are grown on rigid plastic substrates with unrealistic concentration gradients of O2, nutrients, and treatment agents. More importantly, 2D lack cell–cell cell–extracellular matrix (ECM) interactions, which critical for regulating behavior functions. There several three-dimensional (3D) culture systems such as Matrigel, hydrogels, micropatterned plates, hanging drop that overcome these drawbacks but they suffer from technical challenges...
Hepatocyte nuclear factor 4α (HNF4α) is a master regulator of liver function and tumor suppressor in hepatocellular carcinoma (HCC). In this study, we explore the reciprocal negative regulation HNF4α cyclin D1, key cell cycle protein liver. Transcriptomic analysis cultured hepatocyte HCC cells found that D1 knockdown induced expression large network HNF4α-regulated genes. Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated inhibits binding to thousands targets liver, thereby...
It is well established that the liver-specific miR-122, a bona fide tumor suppressor, plays critical role in lipid homeostasis. However, its role, if any, amino acid metabolism has not been explored. Since glutamine (Gln) energy and anaplerotic source for mammalian cells, we assessed Gln control wild type (WT) mice miR-122 knockout (KO) by stable isotope resolved metabolomics (SIRM) studies. Six-to eight-week-old WT KO 12- to 15-month-old liver tumor-bearing were injected with...
Although T cell expansion depends on glycolysis, effector differentiation requires signaling via the production of reactive oxygen species (ROS). Because pentose phosphate pathway (PPP) regulates ROS by generating nicotinamide adenine dinucleotide (NADPH), we examined how PPP blockade affects and function. Here, show that genetic ablation or pharmacologic inhibition enzyme 6-phosphogluconate dehydrogenase (6PGD) in oxidative results generation superior CD8
Cellular metabolism has key roles in T cells differentiation and function. CD4+ helper-1 (Th1), Th2, Th17 subsets are highly glycolytic while regulatory (Tregs) use glucose during expansion but rely on fatty acid oxidation for Upon uptake, can enter pentose phosphate pathway (PPP) or be used glycolysis. Here, we showed that blocking 6-phosphogluconate dehydrogenase (6PGD) the oxidative PPP resulted substantial reduction of Tregs suppressive function shifts toward Th1, phenotypes which led to...
Ammonia emissions contribute to the formation of secondary particulate matter (PM) and violations National Ambient Air Quality Standard. mass concentration measurements were made in February 1999 upwind downwind an open-lot dairy California, using a combination active bubbler passive filter samplers. fluxes calculated from concentrations measured at 2, 4, 10 m above ground three locations on edge dairy, micrometeorological techniques. A new method was developed interpolate six additional...
Immunomodulatory (IM) metabolic reprogramming in macrophages (Mϕs) is fundamental to immune function. However, limited information available for human Mϕs, particularly response plasticity, which critical understanding the variable efficacy of immunotherapies cancer patients. We carried out an in-depth analysis by combining multiplex stable isotope-resolved metabolomics with reversed phase protein array map dynamic changes IM network and key regulators four donors' Mϕs differential...
Cell proliferation requires metabolic reprogramming to accommodate biosynthesis of new cell components, and similar alterations occur in cancer cells. However, the mechanisms linking cycle machinery metabolism are not well defined. Cyclin D1, along with its main partner cyclin-dependent kinase 4 (Cdk4), is a pivotal regulator driver oncogene that overexpressed many cancers. Here, we examine hepatocyte define novel effects cyclin D1 on biosynthetic metabolism. Metabolomic studies reveal...
Abstract Ammonia (NH3) emissions contribute to the formation of secondary particulate matter (PM) 10 μm and under (PM10). Dairies are significant sources NH3 in San Joaquin Valley (SJV) California, where National Ambient Air Quality Standard for PM10 is frequently exceeded. Detailed descriptions diets, animal demographics, production levels were obtained two commercial open-lot dairies SJV used compute nitrogen intake each feeding group (g N day−1). Models derived from nutrition trials with...
Glucose metabolism comprises numerous amphibolic metabolites that provide precursors for not only the synthesis of cellular building blocks but also ATP production. In this study, we tested how phosphofructokinase-1 (PFK1) activity controls fate glucose-derived carbon in murine hearts vivo. PFK1 was regulated by cardiac-specific overexpression kinase- or phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase transgenes mice (termed GlycoLo GlycoHi mice, respectively)....
The loss-of-function mutation of fumarate hydratase (FH) is a driver hereditary leiomyomatosis and renal cell carcinoma (HLRCC). Fumarate accumulation results in activation stress-related mechanisms leading to upregulation survival-related genes. To better understand how cells compensate for the loss FH HLRCC, we determined amino acid nutrient requirements FH-deficient UOK262 line (UOK262) its FH-repleted control (UOK262WT). We growth rates survival lines response depletion supplementation....
Ataxia telangiectasia (A-T) is a rare genetic disorder characterized by neurological defects, immunodeficiency, cancer predisposition, radiosensitivity, decreased blood vessel integrity, and diabetes. ATM, the protein mutated in A-T, responds to DNA damage oxidative stress, but its functional relationship progressive clinical manifestation of A-T not understood. CD98HC chaperones cystine/glutamate (x
Glycogen is a readily deployed intracellular energy storage macromolecule composed of branched chains glucose anchored to the protein glycogenin. Although glycogen primarily occurs in liver and muscle, it found most tissues, its metabolism has been shown be important cancers immune cells. Robust analysis turnover requires stable isotope tracing plus reliable means quantifying total labeled derived from precursors such as 13C6-glucose. Current methods for analyzing are time- sample-consuming,...
Abstract T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic, biosynthetic, and redox demands following antigen stimulation. A robust adaptive immune system requires effector to respond adapt fluctuations in environmental nutrient levels imposed by infectious inflammatory sites different tissues. Inevitably, such responsiveness adaptation reflect plasticity, allowing elicit functions using wide range of substrates. Here, we show utilize...