A5028299159- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Cardiovascular Function and Risk Factors
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Superconducting and THz Device Technology
- ATP Synthase and ATPases Research
- Advanced MEMS and NEMS Technologies
- Muscle metabolism and nutrition
- Cardiomyopathy and Myosin Studies
- Muscle Physiology and Disorders
- Photonic and Optical Devices
- Metabolomics and Mass Spectrometry Studies
- Pancreatic function and diabetes
- Physics of Superconductivity and Magnetism
- Fuel Cells and Related Materials
- Cardiac Fibrosis and Remodeling
- Heart Failure Treatment and Management
- Schizophrenia research and treatment
- Biochemical and Molecular Research
- Semiconductor Lasers and Optical Devices
- Retinoids in leukemia and cellular processes
University of Pennsylvania
2017-2025
Cardiovascular Institute of the South
2018-2025
Children's Hospital of Philadelphia
2024
Hospital of the University of Pennsylvania
2020-2024
University of Glasgow
2023
Goddard Space Flight Center
2009-2022
Thomas Jefferson University
2021
Discovery Institute
2015-2020
Sanford Burnham Prebys Medical Discovery Institute
2011-2020
Translational Therapeutics (United States)
2019
Objective: Recognizing the prodrome of a first psychotic episode prospectively creates opportunity intervention, which could delay, ameliorate or even prevent onset. Valid criteria and reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, Comprehensive Assessment At-Risk Mental States (CAARMS), has been designed such purpose. It two functions: (i) to assess psychopathology thought indicate imminent development first-episode disorder; (ii)...
Cardiac mitochondrial function is altered in a variety of inherited and acquired cardiovascular diseases. Recent studies have identified the transcriptional coactivator peroxisome proliferator–activated receptor γ coactivator-1 (PGC-1) as regulator tissues specialized for thermogenesis, such brown adipose. We sought to determine whether PGC-1 controlled biogenesis energy-producing capacity heart, tissue high-capacity ATP production. found that gene expression induced mouse heart after birth...
Peroxisome proliferator-activated receptor alpha (PPARalpha) plays a key role in the transcriptional control of genes encoding mitochondrial fatty acid beta-oxidation (FAO) enzymes. In this study we sought to determine whether recently identified PPAR gamma coactivator 1 (PGC-1) is capable coactivating PPARalpha FAO Mammalian cell cotransfection experiments demonstrated that PGC-1 enhanced PPARalpha-mediated activation reporter plasmids containing target elements. also transactivation...
Endurance exercise induces increases in mitochondria and the GLUT4 isoform of glucose transporter muscle. Although little is known about mechanisms underlying these adaptations, new information has accumulated regarding how mitochondrial biogenesis expression are regulated. This includes findings that transcriptional coactivator PGC-1 promotes NRF-1 NRF-2 act as activators genes encoding enzymes. We tested hypothesis PGC-1, NRF-1, involved initial adaptive response muscle to exercise. Five...
We hypothesized that the lipid-activated transcription factor, peroxisome proliferator-activated receptor α (PPARα), plays a pivotal role in cellular metabolic response to fasting. Short-term starvation caused hepatic steatosis, myocardial lipid accumulation, and hypoglycemia, with an inadequate ketogenic adult mice lacking PPARα (PPARα −/− ), phenotype bears remarkable similarity of humans genetic defects mitochondrial fatty acid oxidation enzymes. In +/+ mice, fasting induced cardiac...
The gene encoding the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) was targeted in mice. PGC-1alpha null (PGC-1alpha(-/-)) mice were viable. However, extensive phenotyping revealed multi-system abnormalities indicative of an abnormal energy metabolic phenotype. postnatal growth heart and slow-twitch skeletal muscle, organs with high mitochondrial demands, is blunted PGC-1alpha(-/-) With age, develop abnormally increased body...
Recent evidence has defined an important role for PPARα in the transcriptional control of cardiac energy metabolism. To investigate genesis metabolic and functional derangements diabetic cardiomyopathy, mice with cardiac-restricted overexpression (MHC-PPAR) were produced characterized. The expression target genes involved fatty acid uptake oxidation pathways was increased MHC-PPAR mice. Surprisingly, glucose transport utilization reciprocally repressed hearts. Consistent gene profile,...
Recent evidence has defined an important role for PPARα in the transcriptional control of cardiac energy metabolism. To investigate genesis metabolic and functional derangements diabetic cardiomyopathy, mice with cardiac-restricted overexpression (MHC-PPAR) were produced characterized. The expression target genes involved fatty acid uptake oxidation pathways was increased MHC-PPAR mice. Surprisingly, glucose transport utilization reciprocally repressed hearts. Consistent gene profile,...
Background During the development of heart failure (HF), chief myocardial energy substrate switches from fatty acids to glucose. This metabolic switch, which recapitulates fetal cardiac preferences, is thought maintain aerobic energetic balance. The regulatory mechanisms involved in this response are unknown. Methods and Results To characterize expression genes mitochondrial acid β-oxidation (FAO) failing heart, levels mRNA encoding enzymes that catalyze first third steps FAO cycle were...
Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo , due primarily to recruitment of insulin-sensitive transporter (GLUT4) plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4. We show here that adenovirus-mediated expression transcriptional coactivator PGC-1, which expressed but also deficient cells, causes total restoration GLUT4 mRNA levels those observed . This increased correlates with a 3-fold increase transport,...
Background— Significant evidence indicates that the failing heart is energy starved. During development of failure, capacity to utilize fatty acids, chief fuel, diminished. Identification alternate pathways for myocardial fuel oxidation could unveil novel strategies treat failure. Methods and Results— Quantitative mitochondrial proteomics was used identify metabolic derangements occur during cardiac hypertrophy failure in well-defined mouse models. As expected, amounts proteins involved acid...
Medium-chain acyl-CoA dehydrogenase (MCAD) catalyzes a pivotal reaction in mitochondrial fatty acid (FA) beta-oxidation. To examine the potential role of FAs and their metabolites regulation MCAD gene expression, we measured mRNA levels animals fed inhibitors long-chain FA import. Administration carnitine palmitoyltransferase I to mice or rats resulted tissue-limited increases steady-state levels. HepG2 cell cotransfection experiments with promoter reporter plasmids demonstrated that this...
To explore the role of peroxisome proliferator-activated receptor α (PPARα)-mediated derangements in myocardial metabolism pathogenesis diabetic cardiomyopathy, insulinopenic mice with PPARα deficiency (PPARα −/− ) or cardiac-restricted overexpression [myosin heavy chain (MHC)-PPAR] were characterized. Whereas protected from development diabetes-induced cardiac hypertrophy, combination diabetes and MHC-PPAR genotype resulted a more severe cardiomyopathic phenotype than either did alone....
The transcriptional coactivator PPARγ coactivator-1α (PGC-1α) has been characterized as a broad regulator of cellular energy metabolism. Although PGC-1α functions through many transcription factors, the partners identified to date are unlikely account for all its biologic actions. orphan nuclear receptor estrogen-related α (ERRα) was in yeast two-hybrid screen cardiac cDNA library novel PGC-1α-binding protein. ERRα implicated previously regulating gene encoding medium-chain acyl-CoA...
Estrogen-related receptors (ERRs) are orphan nuclear activated by the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) 1α (PGC-1α), a critical regulator of cellular energy metabolism. However, metabolic target genes downstream ERRα have not been well defined. To identify ERRα-regulated pathways in tissues with high demand such as heart, gene expression profiling was performed primary neonatal cardiac myocytes overexpressing ERRα. upregulated subset PGC-1α...
We sought to delineate the molecular regulatory events involved in energy substrate preference switch from fatty acids glucose during cardiac hypertrophic growth. alpha(1)-adrenergic agonist-induced hypertrophy of myocytes culture resulted a significant decrease palmitate oxidation rates and reduction expression gene encoding muscle carnitine palmitoyltransferase I (M-CPT I), an enzyme mitochondrial acid uptake. Cardiac myocyte transfection studies demonstrated that M-CPT promoter activity...
To explore the gene regulatory mechanisms involved in metabolic control of cardiac fatty acid oxidative flux, expression muscle-type carnitine palmitoyltransferase I (M-CPT I) was characterized primary myocytes culture following exposure to long-chain mono-unsaturated acid, oleate. Oleate induced steady-state levels M-CPT mRNA 4.5-fold. The transcription a plasmid construct containing human promoter region fused luciferase reporter transfected into myocytes, over 20-fold by...