A5047956491- Porphyrin Metabolism and Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Neonatal Health and Biochemistry
- Folate and B Vitamins Research
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Metabolism and Genetic Disorders
- Erythrocyte Function and Pathophysiology
- Hemoglobin structure and function
- Methemoglobinemia and Tumor Lysis Syndrome
- Probiotics and Fermented Foods
- Microbial Inactivation Methods
- Trace Elements in Health
- Milk Quality and Mastitis in Dairy Cows
- Listeria monocytogenes in Food Safety
- Meat and Animal Product Quality
- Natural Language Processing Techniques
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Epigenetics and DNA Methylation
- Identification and Quantification in Food
- Blood donation and transfusion practices
- Speech and dialogue systems
- Food Safety and Hygiene
- RNA modifications and cancer
University of Utah
2015-2024
Huntsman Cancer Institute
2017-2023
Primary Children's Hospital
2023
Salt Lake Regional Medical Center
2018
Association of American Medical Colleges
2015
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2015
Creative Commons
2015
Brookhaven National Laboratory
2008
Leicester General Hospital
2008
Georgetown University
2005
Up-regulation of hepatic delta-aminolevulinic acid synthase 1 (ALAS1), with resultant accumulation (ALA) and porphobilinogen, is central to the pathogenesis acute attacks chronic symptoms in porphyria. Givosiran, an RNA interference therapy, inhibits ALAS1 expression.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned symptomatic patients porphyria receive either subcutaneous givosiran (2.5 mg per kilogram body weight) or placebo monthly for 6 months. The primary...
Erythropoietic protoporphyria is a severe photodermatosis that associated with acute phototoxicity. Patients this condition have excruciating pain and markedly reduced quality of life. We evaluated the safety efficacy an α-melanocyte-stimulating hormone analogue, afamelanotide, to decrease improve life.We conducted two multicenter, randomized, double-blind, placebo-controlled trials subcutaneous implants containing 16 mg afamelanotide. in European Union (74 patients) United States (94 were...
Induction of delta aminolevulinic acid synthase 1 (ALAS1) gene expression and accumulation neurotoxic intermediates result in neurovisceral attacks disease manifestations patients with acute intermittent porphyria, a rare inherited heme biosynthesis. Givosiran is an investigational RNA interference therapeutic agent that inhibits hepatic ALAS1 synthesis.
Background and Aims Acute hepatic porphyria comprises a group of rare genetic diseases caused by mutations in genes involved heme biosynthesis. Patients can experience acute neurovisceral attacks, debilitating chronic symptoms, long‐term complications. There is lack multinational, prospective data characterizing the disease current treatment practices severely affected patients. Approach Results EXPLORE prospective, natural history study activity clinical management patients with who...
Iron regulatory proteins (IRP1 and IRP2) are RNA-binding that bind to specific structures, termed iron-responsive elements (IREs), located in the 5′- or 3′-untranslated regions of mRNAs encode involved iron homeostasis. IRP1 IRP2 RNA binding activities regulated by iron; IREs with high affinity iron-depleted cells low iron-repleted cells. The decrease activity occurs a switch between apoprotein 4Fe-4S forms, without changes levels, whereas reflects reduction levels. To determine mechanism...
Hemochromatosis occurs in approximately 5 white people per 1000 and is usually due to homozygosity for mutations the HLA-linked HFE gene. Although screening has been proposed, proportion of homozygotes with conditions related hemochromatosis uncertain.
Significance It has been accepted dogma that eukaryotes and heme-synthesizing bacteria use the same metabolic intermediates in their heme synthesis pathways, where protoporphyrin is final intermediate into which iron inserted to make protoheme. Herein, we present data demonstrating Gram-positive do not as an but, instead, have altered set of terminal reactions oxidize coproporphyrinogen coproporphyrin insert ferrous coproporphyrin, resulting formation coproheme. A newly characterized enzyme,...
Porphyria cutanea tarda (PCT), the most common form of porphyria in humans, is due to reduced activity uroporphyrinogen decarboxylase (URO-D) liver. Previous studies have demonstrated that protein levels URO-D do not change when catalytic reduced, suggesting an inhibitor generated hepatocytes. Here, we describe identification and characterization liver cytosolic extracts from two murine models PCT: wild-type mice treated with iron, delta-aminolevulinic acid, polychlorinated biphenyls; one...
Proteases and lipases from a number of different species psychrotrophic bacteria isolated dairy products are resistant to heat treatments 77°C for holding time 17 s 140°C 5s. A further treatment combining the heating process with involving temperature 55°C 1 h was also examined. The proteases and, lesser extent, were in combination. resistance inactivation by varied between within species. Therefore, this may not have widespread practical application.
The acute hepatic porphyrias are inherited disorders of heme biosynthesis characterized by life-threatening neurovisceral attacks. Factors that induce the expression 5-aminolevulinic acid synthase 1 (ALAS1) result in accumulation neurotoxic porphyrin precursors (ALA) and porphobilinogen (PBG), which recent studies indicate primarily responsible for Current treatment these attacks involves i.v. administration hemin, but a faster-acting, more effective, safer therapy is needed. Here, we...
Heme is an iron-containing cofactor essential for multiple cellular processes and fundamental activities such as oxygen transport. To better understand the means by which heme synthesis regulated during erythropoiesis, affinity purification coupled with mass spectrometry (MS) was performed to identify putative protein partners interacting ferrochelatase (FECH), terminal enzyme in biosynthetic pathway. Both progesterone receptor membrane component 1 (PGRMC1) 2 (PGRMC2) were identified these...
Heme is an essential prosthetic group in proteins that reside virtually every subcellular compartment performing diverse biological functions. Irrespective of whether heme synthesized the mitochondria or imported from environment, this hydrophobic and potentially toxic metalloporphyrin has to be trafficked across membrane barriers, a concept heretofore poorly understood. Here we show, using subcellular-targeted, genetically encoded hemoprotein peroxidase reporters, both extracellular...
Heme is an essential cofactor for most organisms and all metazoans. While the individual enzymes involved in synthesis utilization of heme are fairly well known, less known about intracellular trafficking porphyrins heme, or regulation biosynthesis via protein complexes. To better understand this process we have undertaken a study macromolecular assemblies associated with synthesis. Herein utilized mass spectrometry coimmunoprecipitation tagged biosynthetic pathway developing erythroid cell...
<h3>Importance</h3> Autosomal recessive erythropoietic protoporphyria (EPP) and X-linked (XLP) are rare photodermatoses presenting with variable degrees of painful phototoxicity that markedly affects quality life. The clinical variability, determinants severity, genotype/phenotype correlations these diseases not well characterized. <h3>Objective</h3> To describe the baseline characteristics, genotypes, disease severity in a large patient cohort EPP or XLP. <h3>Design, Setting,...
We present an overview of TARSQI, a modular system for automatic temporal annotation that adds time expressions, events and relations to news texts.
Iron regulatory proteins (IRP1 and IRP2) are RNA-binding that bind to stem-loop structures, termed iron-responsive elements (IREs), present in either the 5'- or 3'-untranslated regions of specific mRNAs. The binding IRPs 5'-IREs inhibits translation mRNA, whereas 3'-IREs stabilizes mRNA. To study structure regulation IRP2, we isolated cDNAs for rat human IRP2. derived amino acid sequence IPR2 is 93% identical with IRP2 lower eukaryotes, indicating highly conserved. IRP1 share 61% overall...