A5060602654- Metabolism and Genetic Disorders
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Mitochondrial Function and Pathology
- Diet and metabolism studies
- Genetics, Aging, and Longevity in Model Organisms
- Molecular spectroscopy and chirality
- ATP Synthase and ATPases Research
- Metabolism, Diabetes, and Cancer
- Glioma Diagnosis and Treatment
- Neurological and metabolic disorders
- Schizophrenia research and treatment
- Cancer-related Molecular Pathways
- Analytical Chemistry and Chromatography
- Cardiovascular Function and Risk Factors
- RNA Research and Splicing
- FOXO transcription factor regulation
- Epilepsy research and treatment
- Protein Degradation and Inhibitors
- Crystallization and Solubility Studies
- Metabolomics and Mass Spectrometry Studies
- Crystallography and molecular interactions
- X-ray Diffraction in Crystallography
- DNA Repair Mechanisms
- Biochemical and Molecular Research
Children's Hospital of Pittsburgh
2022-2024
University of Pittsburgh
2022-2024
Center for Genomic Science
2023
Virginia Tech
2000
University of Namur
1998
MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction maintenance. Although Myc+/- mice are healthier longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe chronic consequences body-wide inactivation initiated postnatally. "MycKO" acquire numerous features premature aging, including altered body composition habitus, metabolic dysfunction, hepatic steatosis, gene...
Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder leading to a block in long-chain fatty acid β-oxidation. Mutations either HADHA and HADHB, which encode the TFPα β subunits, respectively, usually result combined TFP deficiency. A single common mutation, c.1528G>C (p.E510Q), leads isolated 3-hydroxyacyl-CoA dehydrogenase (LCHAD) also catalyzes step remodeling of cardiolipin (CL), phospholipid critical mitochondrial membrane stability function. We...
The "Mlx" and "Myc" transcription factor networks cross-communicate share many common gene targets. Myc's activity depends upon its heterodimerization with Max, whereas the Mlx Network requires that Max-like associate Myc-like factors MondoA or ChREBP. current work demonstrates body-wide inactivation, like of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus metabolism. deregulation Myc target sets is also accelerated. Among other functions, these often regulate...
Abstract Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation (FAO) in humans. Patients exhibit clinical episodes often associated with fasting. Symptoms include hypoketotic hypoglycemia and Reye-like episodes. With limited treatment options, we explored use human MCAD (hMCAD) mRNA fibroblasts from patients to provide functional protein reverse metabolic block. Transfection hMCAD into MCAD- deficient patient cells...
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive disease that prevents the body from utilizing fatty acids for energy, most needed during stress and fasting. Symptoms can appear infancy through childhood adolescence or early adulthood, include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, cardiomyopathy. REN001 a peroxisome-proliferator-activated receptor delta (PPARδ) agonist modulates expression of genes coding acid β-oxidation enzymes...
Summary MYC proto-oncogene dysregulation alters metabolism, translation and other functions in ways that support tumor induction maintenance. Although Myc+/- mice are healthier longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe chronic consequences body-wide inactivation initiated postnatally. “ KO” acquire numerous features premature aging including altered body composition habitus, metabolic dysfunction, hepatic steatosis...
Metabolic reprogramming in pediatric diffuse midline glioma is driven by gene expression changes induced the hallmark histone mutation H3K27M, which results aberrantly permissive activation of oncogenic signaling pathways. Previous studies with altered H3K27 (DMG-H3K27a) have shown that RAS pathway, specifically through its downstream kinase, extracellular-signal-related kinase 5 (ERK5), critical for tumor growth. Further effectors ERK5 and their role DMG-H3K27a metabolic not been explored....
Abstract Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disease that prevents the body from utilizing fatty acids for energy, most needed during stress and fasting. Symptoms can appear infancy through childhood adolescence or early adulthood, include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, cardiomyopathy. REN001 a peroxisome proliferator activated receptor delta (PPARδ) agonist modulates gene expression of acid β-oxidation enzymes...
In order to gain more insight into the mechanisms underlying mitochondrial inhibition by haloperidol (HP) pyridinium metabolites, we have studied three dimensional structure of these compounds. this paper report results experimental (NMR studies in solution, X-ray diffraction) and theoretical methods (molecular dynamics) applied HPP+. The chlorophenyl rings are found not be strictly coplanar a high degree mobility was observed butyroxy chain. Calculations shown that most stable structures...
MYC proto-oncogene dysregulation alters metabolism, translation and other functions in ways that support tumor induction maintenance. Although Myc+/- mice are healthier longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe chronic consequences body-wide inactivation initiated post-natally. “MycKO” acquire numerous features premature aging including altered body composition habitus, metabolic dysfunction, hepatic steatosis gene...
Triheptanoin (triheptanoylglycerol) has shown value as anaplerotic therapy for patients with long chain fatty acid oxidation disorders but is contraindicated in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency. In search MCAD deficiency, fibroblasts from three homozygous the most common mutation, ACADMG985A/G985A, were treated acids hypothesized not to require their metabolism, including heptanoic (C7; active component of triheptanoin), 2,6-dimethylheptanoic (dMC7),...
SummaryMitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder leading to a block in long-chain fatty acid β-oxidation. Mutations either HADHA and HADHB, which encode the TFPα β subunits, respectively, usually result combined TFP deficiency. A single common mutation, c.1528G>C (p.E510Q), leads isolated 3-hydroxyacyl-CoA dehydrogenase (LCHAD) also catalyzes step synthesis of cardiolipin (CL), lipid critical mitochondrial function. We explored effect mutations...
The "Mlx" and "Myc" Networks share many common gene targets. Just as Myc's activity depends upon its heterodimerization with Max, the Mlx Network requires that Max-like factor associate Myc-like factors MondoA or ChREBP. We show here body-wide inactivation, like of Myc, accelerates numerous aging-related phenotypes pertaining to body habitus metabolism. deregulation Myc target sets is also accelerated. Among other functions, these often regulate ribosomal mitochondrial structure function,...
The "reduced" haloperidol pyridinium metabolite (RHPP+) is found in the brain, plasma and urine of patients treated with neuroleptic drug (HP). RHPP+ suspected to be neurotoxic through a mechanism that entails interference mitochondrial electron transport chain. We have studied conformation this flexible molecule solution (using NMR) solid state by single crystal X-ray analysis. Using structure as initial input, molecular dynamics runs indicated preferably exists an unfolded, rather than...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”