A5077828620- Carcinogens and Genotoxicity Assessment
- Toxic Organic Pollutants Impact
- Effects and risks of endocrine disrupting chemicals
- Bioinformatics and Genomic Networks
- Arsenic contamination and mitigation
- Genomics, phytochemicals, and oxidative stress
- Air Quality and Health Impacts
- Epigenetics and DNA Methylation
- Spaceflight effects on biology
- Pharmaceutical and Antibiotic Environmental Impacts
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Safe Handling of Antineoplastic Drugs
- Genomics and Chromatin Dynamics
- Heme Oxygenase-1 and Carbon Monoxide
- Liver Disease Diagnosis and Treatment
- Gene Regulatory Network Analysis
- Non-Destructive Testing Techniques
- Glutathione Transferases and Polymorphisms
- Climate Change and Health Impacts
- Single-cell and spatial transcriptomics
- Computational Drug Discovery Methods
- Heavy Metal Exposure and Toxicity
- Drug-Induced Hepatotoxicity and Protection
- Infrastructure Maintenance and Monitoring
University of Cincinnati Medical Center
2005-2024
Johnson Space Center
2023
University of Cincinnati
2008-2022
Lamar University
2019
Icahn School of Medicine at Mount Sinai
2017
University of Miami
2017
Miami University
2017
National Center for Environmental Assessment (EPA)
2013-2016
University of Colorado Anschutz Medical Campus
2004-2006
University of Colorado Health
1999-2003
Oxidative stress activates the transcription factor NRF2, which in turn binds cis -acting antioxidant response element (ARE) enhancers and induces expression of protective genes. In contrast, transcriptional repressor BACH1 ARE-like cells naïve to oxidative antagonizes NRF2 binding until it becomes inactivated by pro-oxidants. Here, we describe dynamic roles heme oxygenase-1 ( HMOX1 ) gene. induction, elicited arsenite-mediated stress, follows inactivation precedes activation NRF2....
The Library of Integrated Network-based Cellular Signatures (LINCS) program is a national consortium funded by the NIH to generate diverse and extensive reference library cell-based perturbation-response signatures, along with novel data analytics tools improve our understanding human diseases at systems level. In contrast other large-scale generation efforts, LINCS Data Signature Generation Centers (DSGCs) employ wide range assay technologies cataloging cellular responses. Integration of,...
There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses visualization do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an web-based platform analysis of signatures cellular perturbations. The facilitates mining re-analysis the large collection datasets (>34,000), pre-computed (>200,000), their connections, as well user-submitted diseases workflows vast resources range analytics...
The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. naive believed reside in an inactive cytosolic complex translocates the nucleus induces of xenobiotic detoxification genes after activation by ligand.We conducted integrative genomewide analysis AHR gene targets mouse hepatoma cells determined whether regulatory functions may take place absence exogenous ligand.The...
Pharmaceuticals selected for exploration space missions must remain stable and effective throughout mission timeframes. Although there have been six spaceflight drug stability studies, has not a comprehensive analytical analysis of these data. We sought to use studies quantify the rate degradation time-dependent probability failure resulting from loss active pharmaceutical ingredient (API). Additionally, existing were reviewed identify research gaps be addressed prior missions. Data...
Abstract There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses visualization do not require programming skills. Among these, iLINCS is unique in scope versatility of the provided analytics facilitated. ( http://ilincs.org ) an web-based platform analysis signatures cellular perturbations. The facilitates user-submitted diseases perturbations context large compendium pre-computed (>200,000), as well mining...
Intracellular heme is a redox active molecule that can be detrimental to cells at high concentrations or under oxidizing conditions. To prevent accumulation, the inducible enzyme oxygenase-1 (HMOX1) catalyzes degradation of heme. In absence elevated intracellular oxidative stress, basic region leucine zipper transcriptional regulator BACH1 binds HMOX1 antioxidant response elements and represses transcription. Conversely, increased sulfhydryl oxidation inactivate BACH1, permitting induction...
Complex mixtures of carcinogenic metalloids, such as arsenic, and polycyclic aromatic hydrocarbons or halogenated are common environmental contaminants. The biological consequences exposure to these unpredictable and, although the health effects individual chemicals may be known, toxicity is largely unexplored. Arsenic, not a potent mutagen by itself, co-mutagenic with many DNA-damaging agents. Mixtures arsenite plus benzo[<i>a</i>]pyrene (B[<i>a</i>]P) augment B[<i>a</i>]P mutagenicity,...
TCDD and other polyhalogenated aromatic hydrocarbon ligands of the aryl receptor (AHR) have been classically considered as non-genotoxic compounds because they fail to be directly mutagenic in either bacteria or most vitro assay systems. They do so spite having repeatedly linked oxidative stress carcinogenic outcomes. Oxidative stress, on hand, has used a marker for toxicity dioxin its congeners. We focused this review connection between induction toxic effects fetal adult exposure, with...
Pharmaceutical products brought for space missions must remain effective and safe throughout the mission. Previous NASA experiments suggest that radiation exposure could threaten drug stability during long-duration missions. The Exploration Medical Capability (ExMC) Element has evaluated this possibility by exposing four medications to simulated Galactic Cosmic Radiation (GCRSim) at Space Laboratory followed a three-year storage period. solid oral Acetaminophen, Amoxicillin, Ibuprofen,...
Arsenic, first among the top environmentally hazardous substances, is associated with skin, lung, liver, kidney, prostate, and bladder cancer. Arsenic also a cardiovascular central nervous system toxicant, it has genotoxic immunotoxic effects. Paradoxically, arsenic trioxide used successfully in treatment of acute promyelocytic leukemia multiple myeloma. induces oxidative stress, its toxicity decreased by free thiols increased glutathione depletion. To further characterize role stress...
Identifying transcription factors (TF) involved in producing a genome-wide transcriptional profile is an essential step building mechanistic model that can explain observed gene expression data. We developed statistical framework for constructing signatures of TF activity, and using such the analysis data produced by complex regulatory programs. Our integrates ChIP-seq appropriately matched profiles to identify True REGulatory (TREG) TF-gene interactions. It provides quantification...
Previous work has shown that the weight of evidence supports hypothesis 1,4-dioxane causes liver tumors in rodents through cytotoxicity and subsequent regenerative hyperplasia. Questions regarding a lack concordant findings for this mode action (MOA) mice have not been resolved, however. In current work, reanalysis data from two chronic mouse cancer bioassays on 1,4-dioxane, one 13-week study, seven rat bioassays, coupled with other such as 1,4-dioxane's negative mutagenicity, its...
1,4-Dioxane is found in consumer products and used as a solvent manufacturing. Studies rodents show liver tumors to be consistently reported after chronic oral exposure. However, there were differences the reporting of non-neoplastic lesions livers rats mice. In order clarify these differences, reread mouse slides from 1978 NCI bioassay on 1,4-dioxane drinking water was conducted. This clearly identified dose-related changes liver; specifically, increase hypertrophic response hepatocytes,...
(1) Background: Cardio-metabolic diseases (CMD), including cardiovascular disease, stroke, and diabetes, have numerous common individual environmental risk factors. Yet, few studies to date considered how these multiple factors together affect CMD disparities between Blacks Whites. (2) Methods: We linked daily fine particulate matter (PM2.5) measures with survey responses of participants in the Southern Community Cohort Study (SCCS). Generalized linear mixed modeling (GLMM) was used estimate...