Journal Publications

Aug 16

Toward Good Read-Across Practice (GRAP) Guidance

Aug 16, 2017
Grouping of substances and utilizing read-across of data within those groups represents an important data gap filling technique for chemical safety assessments. Categories/analogue groups are typically developed based on structural similarity and, increasingly often, also on mechanistic (biological) similarity. While read-across can play a key role in complying with legislation such as the European REACH

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Aug 16

Stem Cell-Based Methods for Identifying Developmental Toxicity Potential

Aug 16, 2017
There is an increasing need for reliable, high-throughput in vitro developmental toxicity screens in both the pharmaceutical and chemical industries. Establishing predictive human cell-based assays to aid in the early discovery-phase detection of potential developmental toxicants is strongly warranted as these tests could reduce product development time and costs. Stemina authors include Jessica Palmer, Bob

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Aug 16

A human induced pluripotent stem cell-based in vitro assay predicts developmental toxicity through a retinoic acid receptor-mediated pathway for a series of related retinoid analogues

Aug 16, 2017
[Accepted manuscript] The relative developmental toxicity potency of a series of retinoid analogues was evaluated using a human induced pluripotent stem (iPS) cell assay that measures changes in the biomarkers ornithine and cystine. A human induced pluripotent stem cell-based in vitro assay predicts developmental toxicity …

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Aug 16

Supporting Read-Across Using Biological Data

Aug 16, 2017
Read-across, i.e., filling toxicological data gaps by relating to similar chemicals for which test data are available, is usually done based on chemical similarity. Besides structure and physico-chemical properties, biological similarity based on biological data adds extra strength to this process. In the simplest case, chemically similar substances also show similar test results in relevant

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Nov 7

Metabolomics as a Tool for Discovery of Biomarkers of Autism Spectrum Disorder in the Blood Plasma of Children

Nov 7, 2014
PLOS One (November 7, 2014) The diagnosis of autism spectrum disorder (ASD) at the earliest age possible is important for initiating optimally effective intervention. In the United States the average age of diagnosis is 4 years. Identifying metabolic biomarker signatures of ASD from blood samples offers an opportunity for development of diagnostic tests for detection

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Aug 1

Establishment and Assessment of a New Human Embryonic Stem Cell-Based Biomarker Assay for Developmental Toxicity Screening

Aug 1, 2013
Birth Defects Research (Volume 98, Issue 4, August 2013, Pages 343-363) A metabolic biomarker-based in vitro assay utilizing human embryonic stem (hES) cells was developed to identify the concentration of test compounds that perturbs cellular metabolism in a manner indicative of teratogenicity. This assay is designed to aid the early discovery-phase detection of potential human

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Nov 4

The ABCs of membrane transporters in health and disease (SLC series): Introduction

Nov 4, 2012
Molecular Aspects of Medicine (Volume 34, 2013, Pages 95-107) The field of transport biology has steadily grown over the past decade and is now recognized as playing an important role in manifestation and treatment of disease. The SLC (solute carrier) gene series has grown to now include 52 families and 395 transporter genes in the

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Sep 23

The sodium-dependent ascorbic acid transporter family SLC23

Sep 23, 2012
Molecular Aspects of Medicine (Volume 34, 2013, Pages 436-454) Transporters for vitamin C and its oxidized form dehydroascorbic acid (DHA) are crucial to maintain physiological concentrations of this important vitamin that is used in a variety of biochemical processes. The human SLC23 family consists of the Na+-dependent vitamin C transporters SVCT1 (encoded by the SLC23A1

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Aug 15

Metabolomics in Toxicology and Preclinical Research

Aug 15, 2012
ALTEX: Alternatives to Animal Experimentation (Article in Press) Metabolomics, the comprehensive analysis of metabolites in a biological system, provides detailed information about the biochemical/physiological status of a biological system, and about the changes caused by chemicals. Metabolomics analysis is used in many fields, ranging from the analysis of the physiological status of genetically modified organisms

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Aug 11

Metabolic Biomarkers of Prenatal Alcohol Exposure in Human Embryonic Stem Cell–Derived Neural Lineages

Aug 11, 2012
Alcoholism: Clinical and Experimental Research (Volume 36, Issue 8, August 2012, Pages 1314-24) Fetal alcohol spectrum disorders (FASD) are a leading cause of neurodevelopmental disability. The mechanisms underlying FASD are incompletely understood, and biomarkers to identify those at risk are lacking. Here, we perform metabolomic analysis of embryoid bodies and neural lineages derived from human

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Jan 26

A Roadmap for the Development of Alternative (Non-Animal) Methods for Systemic Toxicity Testing

Jan 26, 2012
ALTEX: Alternatives to Animal Experimentation (Volume 29, Issue 1, January 2012, Pages 5-91) Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as

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Nov 15

Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

Nov 15, 2011
Toxicology and Applied Pharmacology Volume 257, Issue 1, 15 November 2011, Pages 111-121 Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA’s ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultures were evaluated

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Aug 15

Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics

Aug 15, 2010
Toxicology and Applied Pharmacology Volume 247, Issue 1, 15 August 2010, Pages 18-27. Teratogens, substances that may cause fetal abnormalities during development, are responsible for a significant number of birth defects. Animal models used to predict teratogenicity often do not faithfully correlate to human response. Here, we seek to develop a more predictive developmental toxicity

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Dec 25

Identification of Small Molecules from Human Embryonic Stem Cells Using Metabolomics

Dec 25, 2007
Stem Cells and Development Volume 16, Issue 6, 25 December 2007, Pages 869-882 Metabolomics enables the discovery of small molecules that may serve as candidate biomarkers of pharmacological efficacy or toxicity. Biochemical pathways of human development are likely active in human embryonic stem (hES) cells and derivatives, since they recapitulate organogenesis in vitro. We hypothesized

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Mar 2

Embryonic Stem Cells in Predictive Cardiotoxicity: Laser Capture Microscopy Enables Assay Development

Mar 2, 2006
Toxicological Sciences Volume 90, Issue 1, March 2006, Pages 149-158 Embryonic stem (ES) cells offer unprecedented opportunities for in vitro drug discovery and safety assessment of compounds. Cardiomyocytes derived from ES cells enable development of predictive cardiotoxicity models to increase the safety of novel drugs. Heterogeneity of differentiated ES cells limits the development of reliable

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