A5089145597- Hormonal Regulation and Hypertension
- Cardiac tumors and thrombi
- Adrenal and Paraganglionic Tumors
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Peptidase Inhibition and Analysis
- Diabetes Treatment and Management
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Diet and metabolism studies
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Protein Kinase Regulation and GTPase Signaling
- Memory and Neural Mechanisms
- Nicotinic Acetylcholine Receptors Study
- Adrenal Hormones and Disorders
- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Congenital heart defects research
- Cancer, Hypoxia, and Metabolism
- Pharmacological Effects of Natural Compounds
- Ion Transport and Channel Regulation
- Neuropeptides and Animal Physiology
- Genomics and Rare Diseases
- Antioxidant Activity and Oxidative Stress
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2013-2025
National Institutes of Health
2013-2025
Government of the United States of America
2024
Pediatrics and Genetics
2020
University of Maryland, College Park
2006-2010
Center for Food Safety and Applied Nutrition
2006
Carney complex (CNC) is a multiple neoplasia syndrome caused by PRKAR1A-inactivating mutations. One-third of the patients, however, have no detectable PRKAR1A coding sequence defects. Small deletions gene were previously reported in few but large chromosomal locus not been studied systematically cohort patients with CNC.A tertiary care referral center was setting for analysis an international CNC.Methods included genome-wide array followed fluorescent situ hybridization, mRNA, and other...
The increased prevalence of overweight and obesity in the United States during past three decades coincides with a trend sugar intake, especially fructose, leading to speculation that two trends may be linked. enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1), regulates intracellular tissue‐specific glucocorticoid levels, is adipose suppressed liver obese humans animals. Hexose‐6‐phosphate (H6PDH) colocalized 11β‐HSD1 generates nicotinamide adenosine dinucleotide phosphate, required...
The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism all organ systems affected by obesity. PKA four regulatory (RIα, RIIα, RIβ, RIIβ) catalytic (Cα, Cβ, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIβ, the primary adipose tissue or Cβ resulted lean phenotype resists diet-induced obesity associated metabolic complications. Here we report disruption...
The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations drive emotion, reward addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels brain, remarkably little known as how they impact mHb/IPN circuit function at granular level. In this study, our systematic functional pharmacogenetic analyses demonstrate that mOR...
The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations drive emotion, reward addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels brain, remarkably little known as how they impact mHb/IPN circuit function at granular level. In this study, our systematic functional pharmacogenetic analyses demonstrate that mOR...
Carney complex (CNC) is a rare disease associated with multiple neoplasias, including predisposition to pancreatic tumors; it caused most frequently by the inactivation of PRKAR1A gene, regulator cyclic AMP (cAMP)-dependent kinase (PKA). The method used was create null alleles prkar1a in mouse cells expressing pdx1 (Δ-Prkar1a). We found that these mice developed endocrine or mixed endocrine/acinar cell carcinomas 100% penetrance age 4-5 months. Malignant behavior tumors seen as evidenced...
We characterize the clinical and molecular phenotypes of six unrelated individuals with intellectual disability autism spectrum disorder who carry heterozygous missense variants PRKAR1B gene, which encodes R1β subunit cyclic AMP-dependent protein kinase A (PKA).
Abstract Familial primary aldosteronism (PA) is rare and mostly diagnosed in early-onset hypertension (HT). However, ‘sporadic’ bilateral adrenal hyperplasia (BAH) the most frequent cause of PA remains without genetic etiology cases. Our aim was to investigate new defects associated with BAH PA. We performed whole-exome sequencing (paired blood tissue) six patients caused by that underwent unilateral adrenalectomy. Additionally, we conducted functional studies hyperplastic tissue transfected...
SUMMARY Within the adult rodent hippocampus, opioids suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting local micro-circuits. However, it is unknown if this disinhibitory motif conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition robustly suppressed by hippocampus proper but not primary neocortex mice and nonhuman primates, with spontaneous tone resected human tissue also following a consistent...
Opioid receptors within the CNS regulate pain sensation and mood are key targets for drugs of abuse. Within adult rodent hippocampus (HPC), μ-opioid receptor agonists suppress inhibitory parvalbumin-expressing interneurons (PV-INs), thus disinhibiting circuit. However, it is uncertain if this disinhibitory motif conserved in other cortical regions, species, or across development. We observed that PV-IN mediated inhibition robustly suppressed by opioids HPC but not neocortex mice nonhuman...
The cAMP signaling pathway is implicated in bilateral adrenocortical hyperplasias. Bilateral hyperplasia often associated with ACTH-independent Cushing syndrome (CS) and may be caused by mutations genes such as PRKAR1A, which responsible for primary pigmented nodular disease (PPNAD). PRKAR1A regulates cAMP-dependent protein kinase (PKA), an essential enzyme the regulation of adiposity. Although CS invariably obesity, its different forms, including those PKA defects, have not been...
To investigate how supplementation of the monkey's diet with high doses lutein (L), zeaxanthin (Z), or a combination two affects plasma levels and ocular tissue deposition these carotenoids their metabolites over time to determine whether can cause toxicity.Eighteen female rhesus monkeys were divided into groups control (n = 3 control), L-treated 5, 9.34 mg lutein/kg 0.66 zeaxanthin/kg), Z-treated 10 L/Z-treated zeaxanthin, each 0.5 mg/kg). After 12 months daily supplementation, one animal,...
The cAMP-dependent protein kinase (PKA) is an essential regulator of lipid and glucose metabolism that plays a critical role in energy homeostasis. impact diet on PKA signaling has not been defined, although perturbations individual subunits are associated with changes adiposity, physical activity intake mice humans. We hypothesized high fat (HFD) would elicit peripheral central alterations the system differ depending length exposure to HFD; these differences could protect against or promote...
Genetic variants in components of the protein kinase A (PKA) enzyme have been associated with various defects and neoplasms context Carney complex (CNC) isolated cases, such as primary pigmented nodular adrenocortical disease (PPNAD), cortisol-producing adrenal adenomas (CPAs), cancers. PRKAR1A mutations found subjects impaired cAMP-dependent signaling skeletal defects; bone tumors also develop both humans mice PKA abnormalities. We studied PRKACB gene 148 PPNAD related disorders, who did...
Carney complex (CNC) is a syndrome characterized by hyperplasia of endocrine organs and may present with clinical features Cushing acromegaly due to functional adrenal pituitary gland tumors. CNC has been linked mutations in the regulatory subunit protein kinase A type I-alpha (PRKAR1A) gene.Tissue samples were taken from hypothalamus or thalamus tumors patients adenomas seen operated on neurosurgeon Harvey between 1913 1932. Following DNA extraction, sequencing for genes interest was...
The protein kinase A (PKA) signaling system mediates the effects of numerous hormones, neurotransmitters, and other molecules to regulate metabolism, cardiac function, more. PKA defects may lead diverse phenotypes that largely depend on unique expression profile affected subunit. Deletion Prkarcb gene, which codes for catalytic subunit β (Cβ), protects against diet-induced obesity (DIO), yet mechanism this phenotype remains unclear. We hypothesized metabolic rate would be increased in Cβ...
The habenula (Hb) is a bilateral, evolutionarily conserved epithalamic structure connecting forebrain and midbrain structures that has gained attention for its roles in depression, addiction, rewards processing, motivation. Of 2 major subdivisions, the medial Hb (MHb) lateral (LHb), MHb circuitry function are poorly understood relative to those of LHb. Prkar2a codes cAMP-dependent protein kinase (PKA) regulatory subunit IIα (RIIα), component PKA holoenzyme at center one cell-signaling...