A5040020286- Trace Elements in Health
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Heavy Metal Exposure and Toxicity
- Amyotrophic Lateral Sclerosis Research
- Erythropoietin and Anemia Treatment
- Neurological diseases and metabolism
- Alzheimer's disease research and treatments
- Environmental Toxicology and Ecotoxicology
- Parkinson's Disease Mechanisms and Treatments
- Metal-Catalyzed Oxygenation Mechanisms
- Prion Diseases and Protein Misfolding
- Folate and B Vitamins Research
- Photosynthetic Processes and Mechanisms
- Plant Micronutrient Interactions and Effects
- Mitochondrial Function and Pathology
- Drug Transport and Resistance Mechanisms
- Pregnancy and preeclampsia studies
- Bacillus and Francisella bacterial research
- Porphyrin Metabolism and Disorders
- Cancer-related molecular mechanisms research
- Inhalation and Respiratory Drug Delivery
- Microbial Fuel Cells and Bioremediation
- Erythrocyte Function and Pathophysiology
- RNA regulation and disease
Brown University
2014-2025
John Brown University
2014-2025
North Carolina State University
2015
Boston Children's Hospital
2010-2012
Boston University
2012
Harvard University
2011
Noble (United States)
2010
Lerøy (Norway)
2006
Washington University in St. Louis
2000-2006
Mallinckrodt (United States)
1999-2003
Recent studies in Saccharomyces cerevisiae suggest that the delivery of copper to Cu/Zn superoxide dismutase (SOD1) is mediated by a cytosolic protein termed chaperone for (CCS). To determine role CCS mammalian homeostasis, we generated mice with targeted disruption alleles ( −/− mice). Although are viable and possess normal levels SOD1 protein, they reveal marked reductions activity when compared control littermates. Metabolic labeling 64 Cu demonstrated reduction direct result impaired...
Prion diseases are neurodegenerative disorders that result from conformational transformation of a normal cell surface glycoprotein, PrP<sup>C</sup>, into pathogenic isoform, PrP<sup>Sc</sup>. Although the physiological function PrP<sup>C</sup> has remained enigmatic, recent observation protein binds copper ions with micromolar affinity suggests possible role in brain metabolism. In this study, we have used mice express 0, 1, and 10 times level PrP to assess effect expression on amount...
Manganese (Mn), an essential metal and nutrient, is toxic in excess. Toxicity classically results from inhalational exposures individuals who work industrial settings. The first known disease of inherited Mn excess, identified 2012, caused by mutations the exporter SLC30A10 characterized dystonia, cirrhosis, polycythemia. To investigate role homeostasis, we generated whole-body Slc30a10–deficient mice, which developed severe excess impaired systemic biliary excretion. Slc30a10 localized to...
Abstract Manganese (Mn) is an essential trace element required for various biological functions, but excessive Mn levels are neurotoxic and lead to significant health concerns. The mechanisms underlying Mn-induced neurotoxicity remain poorly understood. Neuropathological studies of affected brain regions reveal astrogliosis, neuronal loss, along with evidence neuroinflammation. Here, we present a novel Mn-dependent mechanism linking mitochondrial dysfunction We found that disrupts...
The copper chaperone for superoxide dismutase (CCS) is an intracellular metallochaperone required incorporation of into the essential antioxidant enzyme copper/zinc (SOD1). Nutritional studies have revealed that abundance CCS inversely proportional to dietary and tissue content. To determine mechanisms copper-dependent regulation CCS, SOD1 enzymatic activity as well half-life were determined after metabolic labeling CCS-/- fibroblasts transfected with wild-type or mutant CCS. Wild-type...
The manganese (Mn) export protein SLC30A10 is essential for Mn excretion via the liver and intestines. Patients with deficiency develop excess, dystonia, disease, polycythemia. Recent genome-wide association studies revealed a link between variant T95I markers of disease. in vivo relevance this has yet to be investigated. Using vitro models, we explore impact on function. While I95 expressed at lower levels than T95 transfected cell lines, both variants protected cells similarly from...
A gene cluster which includes genes required for the expression of nitric oxide reductase in Rhodobacter sphaeroides 2.4.3 has been isolated and characterized. Sequence analysis indicates that two proximal are Nor structural genes. These four distal apparently constitute an operon. Mutational genes, norC norB, immediately downstream, norQ norD, active complex. The remaining nnrT nnrU, both Nir Nor. products norCBQD have significant identity with from other denitrifiers, whereas predicted...
Copper/zinc superoxide dismutase (SOD1) is an abundant intracellular enzyme with essential role in antioxidant defense. The activity of SOD1 dependent upon the presence a bound copper ion incorporated by chaperone for dismutase, CCS. To elucidate cell biological mechanisms this process, synthesis and turnover were examined following 64Cu metabolic labeling fibroblasts derived from CCS +/+ –/– embryos. data indicate that rapidly into both newly synthesized preformed apoprotein, each process...
Iron is essential for erythropoiesis and other biological processes, but toxic in excess. Dietary absorption of iron a highly regulated process major determinant body levels. excretion, however, considered passive, unregulated process, the underlying pathways are unknown. Here we investigated role metal transporters SLC39A14 SLC30A10 biliary excretion. While imports manganese into liver organs under physiological conditions, it conditions exports from hepatocytes bile. We hypothesized that...
The innate immune system in humans consists of both cellular and humoral components that collaborate to eradicate invading bacteria from the body. Here, we discover Gram-positive bacterium Bacillus anthracis, causative agent anthrax, does not grow human serum. Fractionation serum by gel filtration chromatography led identification transferrin as inhibiting factor. Purified blocks growth fully virulent encapsulated B. anthracis Ames non-encapsulated Sterne strain. Growth inhibition was also...
Mice have been essential for distinguishing the role of hepcidin in iron homeostasis. Currently, investigators monitor levels murine hepatic hepcidin-1 mRNA as a surrogate marker bioactive protein itself. Here, we describe and validate competitive, enzyme-linked immunosorbent assay that quantifies mouse serum urine. The exhibits biologically relevant lower limit detection, high precision, excellent linearity recovery. We also demonstrate correlation between urine values competitive by...
Manganese is an essential yet potentially toxic metal. Initially reported in 2012, mutations SLC30A10 are the first known inherited cause of manganese excess. apical membrane protein that exports from hepatocytes into bile and enterocytes lumen gastrointestinal tract. deficiency results impaired excretion, leading to excess, neurologic deficits, liver cirrhosis, polycythemia, erythropoietin Neurologic disease attributed toxicity. Polycythemia The goal this study was determine basis excess...
Upstream of the nor and nnrR cluster in Rhodobacter sphaeroides 2.4.3 is a previously uncharacterized gene that has been designated nnrS. nnrS only expressed when grown under denitrifying conditions. Expression dependent on transcriptional regulator NnrR, which also regulates expression genes required for reduction nitrite to nitrous oxide, including nirK nor. Deletion analysis indicated sequence 5′-TTGCG(N4)CACAA-3′, similar sequences found nor, expression. Mutation this consensus...
Concerns exist as to whether individuals may be at greater risk for neurotoxicity following increased manganese (Mn) oral intake. The goals of this study were determine the equivalence 3 methods exposure and rate (mg Mn/kg/day) exposure. Adult male rats allocated control diet (10 ppm), high (200 manganese-supplemented drinking water, gavage treatment groups. Animals in water groups given 10 ppm supplemented with chloride (MnCl2) or once-daily provide a daily intake equivalent that seen...