David M. Koeller
A5013853357- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- Amino Acid Enzymes and Metabolism
- Biochemical and Molecular Research
- Folate and B Vitamins Research
- RNA and protein synthesis mechanisms
- Genomics and Rare Diseases
- Metabolomics and Mass Spectrometry Studies
- RNA modifications and cancer
- RNA regulation and disease
- Neonatal Health and Biochemistry
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- Diet and metabolism studies
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Congenital heart defects research
- Glycosylation and Glycoproteins Research
- Biomedical Text Mining and Ontologies
- Congenital Diaphragmatic Hernia Studies
- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Iron Metabolism and Disorders
Oregon Health & Science University
2013-2023
Doernbecher Children's Hospital
2006-2016
Universidade Federal do Rio Grande do Sul
2014
Agence de Médecine Préventive
2014
University of Portland
2006
University of Colorado Health
1995-2000
University of Washington
1991-1999
Frederick National Laboratory for Cancer Research
1999
University of Missouri–Kansas City
1995
Children's Mercy Hospital
1995
The biosynthetic rates for both the transferrin receptor (TfR) and ferritin are regulated by iron. An iron-responsive element (IRE) in 5′ untranslated portion of messenger RNA (mRNA) mediates iron-dependent control its translation. In this report 3′ region mRNA human TfR was shown to be necessary sufficient levels. Deletion studies identified a 678-nucleotide fragment complementary DNA that is critical iron regulation. Five potential stem-loops resemble IRE contained within Each two five...
X-linked sideroblastic anemia and ataxia (XLSA/A) is a recessive disorder characterized by an infantile to early childhood onset of non-progressive cerebellar mild with hypochromia microcytosis. A gene encoding ATP-binding cassette (ABC) transporter was mapped Xq13, region previously shown linkage analysis harbor the XLSA/A gene. This gene, ABC7, ortholog yeast ATM1 whose product localizes mitochondrial inner membrane involved in iron homeostasis. The full-length ABC7 cDNA cloned entire...
Thymidylate synthase (TS; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) is essential for the de novo synthesis of thymidylate, a precursor DNA. Previous studies have shown that cellular level this protein regulated at both transcriptional and posttranscriptional levels. The regulation human TS mRNA translation was studied in vitro with rabbit reticulocyte lysate system. addition purified recombinant to reactions inhibited mRNA. This inhibition specific had no effect...
<h3>Background</h3> Fabry disease is an X-linked lysosomal storage disorder caused by <i>GLA</i> mutations, resulting in α-galactosidase (α-Gal) deficiency and accumulation of substrates. Migalastat, oral pharmacological chaperone being developed as alternative to intravenous enzyme replacement therapy (ERT), stabilises specific mutant (<i>amenable</i>) forms α-Gal facilitate normal trafficking. <h3>Methods</h3> The main objective the 18-month, randomised, active-controlled ATTRACT study was...
Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply multidisciplinary model in the evaluation of most challenging cases and identify biologic characteristics newly discovered diseases. UDN, which is funded by National Institutes Health, formed 2014 as network seven clinical sites, two sequencing cores, coordinating center. Later, central biorepository, metabolomics core, organisms screening center were added.
The level of mRNA encoding the transferrin receptor (TfR) is regulated by iron, and this regulation mediated a portion 3' untranslated region (UTR) TfR transcript. This UTR human contains five RNA elements that have structural similarity to iron-responsive element (IRE) found as single copy in 5' for ferritin, whose translation iron. Moreover, very similar are also contained chicken mRNA. Cytosolic extracts cell lines shown gel shift assay involving RNase T1 protection contain an IRE-binding...
DNA regions of 10 and 7 kb that flank the mouse metallothionein II (MT-II) MT-I genes, respectively, were combined with a minimally marked (MT-I*) gene tested in transgenic mice. This construct resulted (i) position-independent expression MT-I* mRNA copy number-dependent expression, (ii) levels hepatic per cell transgene about half derived from endogenous (iii) appropriate regulation by metals hormones, (iv) tissue distribution resembled mRNA. These features not observed when was without...
Previous studies from this laboratory have shown that human TS mRNA translation is regulated by its protein product in a negative autoregulatory manner. In paper, we identify an RNA binding site for located within the first 188 nt of RNA. A 36-nt sequence contained 188-nt fragment, corresponding to 75-110 and including translational initiation site, binds with affinity similar both full-length sequences. Variant RNAs either deletion or mutation at region are unable compete binding. UV...
Since many lines of evidence suggest that expression the transforming growth factor-beta 1 (TGF-beta 1) gene may be regulated post-transcriptionally, we examined effect 5'-untranslated region (UTR) this on TGF-beta expression. For purpose, fragments 840-nucleotide highly GC-rich 5'-UTR were inserted into structural for human hormone driven by simian virus 40 early promoter. A portion mRNA spanning sequences from +11 to +147 was shown inhibit as much 22-fold. This cell-specific; production...
Abstract Glutaric acid (GA) and 3‐hydroxyglutaric acids (3‐OH‐GA) are key metabolites in glutaryl co‐enzyme A dehydrogenase (GCDH) deficiency both considered to be potential neurotoxins. As cerebral concentrations of GA 3‐OH‐GA have not yet been studied systematically, we investigated the tissue‐specific distribution these organic glutarylcarnitine brain, liver, skeletal heart muscle Gcdh ‐deficient mice as well hepatic –/– C57Bl/6 following intraperitoneal loading. Furthermore, determined...
Glutaric acidemia type I (GA-I) is an autosomal recessive disorder of amino acid metabolism resulting from a deficiency glutaryl-CoA dehydrogenase (GCDH). Patients accumulate glutaric (GA) and 3-OH (3-OHGA) in their blood, urine CSF. Clinically, GA-I characterized by macrocephaly, progressive dystonia dyskinesia. Degeneration the caudate putamen basal ganglia, widening Sylvian fissures, fronto-temporal atrophy severe spongiform change white matter are also commonly observed. In this report...
Turnover of the full-length human transferrin receptor (TfR) mRNA is regulated by iron, and this regulation mediated transcript's 3' untranslated region. Alterations in sequence TfR regulatory region have been identified that render unregulated iron intrinsically unstable. When cells expressing unstable are treated with inhibitors protein synthesis (cycloheximide or puromycin), steady-state level encoded increased due to a stabilization transcript. A similar set observations has made using...
Inherited deficiency of glutaryl-CoA dehydrogenase results in an accumulation glutaryl-CoA, glutaric, and 3-hydroxyglutaric acids. If untreated, most patients suffer acute encephalopathic crisis and, subsequently, striatal damage being precipitated by febrile infectious diseases during a vulnerable period brain development (age 3 36 months). It has been suggested before that some these organic acids may induce excitotoxic cell damage, however, the relevance bioenergetic impairment is not yet...
Glutaric aciduria type I, an inherited deficiency of glutaryl-coenzyme A dehydrogenase localized in the final common catabolic pathway L-lysine, L-hydroxylysine and L-tryptophan, leads to accumulation neurotoxic glutaric 3-hydroxyglutaric acid, as well non-toxic glutarylcarnitine. Most untreated patients develop irreversible brain damage during infancy that can be prevented majority cases if metabolic treatment with a low L-lysine diet L-carnitine supplementation is started newborn period....
ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a of synthase and plays an important role in coupling proton translocation production. Here, we describe two individuals, each with homozygous missense variants ATP5F1D, who presented episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, hyperammonemia. Subject 1, for c.245C>T (p.Pro82Leu), recurrent decompensation starting the neonatal period, subject 2, c.317T>G (p.Val106Gly),...