Michael B. Black
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View article: Transcriptomic re-analyses of human hepatocyte spheroids treated with PFAS reveals chain length and dose-dependent modes of action
Transcriptomic re-analyses of human hepatocyte spheroids treated with PFAS reveals chain length and dose-dependent modes of action Open
To identify pathway perturbations and examine biological modes of action (MOAs) for various perfluoroalkyl substances, we re-analyzed published in vitro gene expression studies from human primary liver spheroids. With treatment times rangi…
View article: Integrating gene expression and splicing dynamics across dose-response oxidative modulators
Integrating gene expression and splicing dynamics across dose-response oxidative modulators Open
Toxicological risk assessment increasingly utilizes transcriptomics to derive point of departure (POD) and modes of action (MOA) for chemicals. One essential biological process that allows a single gene to generate several different RNA is…
View article: Investigating the mode of action for liver toxicity and wasting-like responses produced by high dose exposures to longer chain perfluoroacid substances (PFAS) using high throughput transcriptomics
Investigating the mode of action for liver toxicity and wasting-like responses produced by high dose exposures to longer chain perfluoroacid substances (PFAS) using high throughput transcriptomics Open
Single doses of perfluoro-n-decanoic acid (PFDA) cause wasting, a progressive loss of 30 to 50% body weight, increasing liver/body weight ratios, and death within several weeks (Olson and Andersen, 1983). Repeat high doses of perfluoroocta…
View article: Investigating the mode of action for wasting produced by tetrachlorodibenzo-p-dioxin (TCDD) in rats using transcriptomics: Evidence for roles of AHR and ARNT in circadian cycling
Investigating the mode of action for wasting produced by tetrachlorodibenzo-p-dioxin (TCDD) in rats using transcriptomics: Evidence for roles of AHR and ARNT in circadian cycling Open
Single, high doses of TCDD in rats caused wasting, a progressive loss of 30 to 50% body weight and death within several weeks. To identify pathway perturbations at or near doses causing wasting, we examined differentially gene expression (…
View article: Mining toxicogenomic data for dose-responsive pathways: implications in advancing next-generation risk assessment
Mining toxicogenomic data for dose-responsive pathways: implications in advancing next-generation risk assessment Open
Introduction: While targeted investigation of key toxicity pathways has been instrumental for biomarker discovery, unbiased and holistic analysis of transcriptomic data provides a complementary systems-level perspective. However, in a syst…
View article: Impact of gene selection criteria on transcriptomic ontology-based point of departure estimates
Impact of gene selection criteria on transcriptomic ontology-based point of departure estimates Open
Apical effects are typically associated with changes in gene expression, which allows for the use of short- term in life transcriptomic studies to derive biologically relevant points of departure (POD). These methods offer cost savings ove…
View article: Assessing the basal gene expression of cancer cell lines for in vitro transcriptomic toxicology screening
Assessing the basal gene expression of cancer cell lines for in vitro transcriptomic toxicology screening Open
In vitro toxicology has used immortalized cancer cell lines as model human systems for decades. However, these cell lines pose problems in designing toxicity testing programs as they inherently do not represent normal human biology. There …
View article: Table 1 in A new Gammarus species from Xinjiang Uygur Autonomous Region (China) with a key to Xinjiang freshwater gammarids (Crustacea, Amphipoda, Gammaridae)
Table 1 in A new Gammarus species from Xinjiang Uygur Autonomous Region (China) with a key to Xinjiang freshwater gammarids (Crustacea, Amphipoda, Gammaridae) Open
Table 1. Primer sequences of PCR products for target genes. GenePrimerSequence (5'-3')ReferenceCO1LCO1490GGTCAACAAATCATAAAGATATTGGFolmer et al. (1994)HCO2198TAAACTTCAGGGTGACCAAAAAATFolmer et al. (1994)LCO3TCNACHAAYCATAAAGAYATTGGTACKrebes e…
View article: Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology
Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology Open
There is increasing interest in using modern 'omics technologies, such as whole transcriptome sequencing, to inform decisions about human health safety and chemical toxicity hazard. High throughput methodologies using in vitro assays offer…
View article: A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidozole
A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidozole Open
The National Toxicology Program (NTP) reported that chronic dietary exposure to 4-methylimidazole (4-MeI) increased the incidence of lung adenomas/carcinomas beyond the normally high spontaneous rate in B6C3F1 mice. To examine plausible mo…
View article: Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures
Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures Open
Because of their broad biological coverage and increasing affordability transcriptomic technologies have increased our ability to evaluate cellular response to chemical stressors, providing a potential means of evaluating chemical response…
View article: A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation Open
Efficient high-throughput transcriptomics (HTT) tools promise inexpensive, rapid assessment of possible biological consequences of human and environmental exposures to tens of thousands of chemicals in commerce. HTT systems have used relat…
View article: Assessing bioactivity-exposure profiles of fruit and vegetable extracts in the BioMAP profiling system
Assessing bioactivity-exposure profiles of fruit and vegetable extracts in the BioMAP profiling system Open
The ToxCast program has generated in vitro screening data on over a thousand chemicals to assess potential disruption of important biological processes and assist in hazard identification and chemical testing prioritization. Few results ha…
View article: Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment
Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment Open
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting …
View article: Assessing molecular initiating events (MIEs), key events (KEs) and modulating factors (MFs) for styrene responses in mouse lungs using whole genome gene expression profiling following 1-day and multi-week exposures
Assessing molecular initiating events (MIEs), key events (KEs) and modulating factors (MFs) for styrene responses in mouse lungs using whole genome gene expression profiling following 1-day and multi-week exposures Open
Styrene increased lung tumors in mice at chronic inhalation exposures of 20ppm and greater. MIEs, KEs and MFs were examined using gene expression in three strains of male mice (the parental C57BL/6 strain, a CYP2F2(-/-) knock out and a CYP…
View article: Combining transcriptomics and PBPK modeling indicates a primary role of hypoxia and altered circadian signaling in dichloromethane carcinogenicity in mouse lung and liver
Combining transcriptomics and PBPK modeling indicates a primary role of hypoxia and altered circadian signaling in dichloromethane carcinogenicity in mouse lung and liver Open
Dichloromethane (DCM) is a lung and liver carcinogen in mice at inhalation exposures≥2000ppm. The modes of action (MOA) of these responses have been attributed to formation of genotoxic, reactive metabolite(s). Here, we examined gene expre…
View article: Editor’s Highlight: Screening ToxCast Prioritized Chemicals for<i>PPARG</i>Function in a Human Adipose-Derived Stem Cell Model of Adipogenesis
Editor’s Highlight: Screening ToxCast Prioritized Chemicals for<i>PPARG</i>Function in a Human Adipose-Derived Stem Cell Model of Adipogenesis Open
The developmental origins of obesity hypothesis posits a multifaceted contribution of factors to the fetal origins of obesity and metabolic disease. Adipocyte hyperplasia in gestation and early childhood may result in predisposition for ob…