A5065931037- HIV/AIDS drug development and treatment
- Protein Degradation and Inhibitors
- Fungal and yeast genetics research
- Trace Elements in Health
- Multiple Myeloma Research and Treatments
- Environmental Toxicology and Ecotoxicology
- HIV Research and Treatment
- Plant Micronutrient Interactions and Effects
- Radioactive element chemistry and processing
- DNA Repair Mechanisms
- Chromium effects and bioremediation
- Molecular Biology Techniques and Applications
- Lanthanide and Transition Metal Complexes
- Hemoglobinopathies and Related Disorders
- Endoplasmic Reticulum Stress and Disease
- Carcinogens and Genotoxicity Assessment
- Plant Gene Expression Analysis
- Genomics, phytochemicals, and oxidative stress
- Iron Metabolism and Disorders
- Research on Leishmaniasis Studies
- CRISPR and Genetic Engineering
- Microbial Metabolic Engineering and Bioproduction
- Indoor Air Quality and Microbial Exposure
- Pharmaceutical and Antibiotic Environmental Impacts
- Geochemistry and Elemental Analysis
University of Florida
2017-2024
Florida College
2021
University of California, Berkeley
2007-2018
United States Army
2009
Jackson State University
2009
U.S. Army Engineer Research and Development Center
2009
Iron and copper are essential nutrients for life as they required the function of many proteins but can be toxic if present in excess. Accumulation these metals human body a consequence overload disorders and/or high environmental exposures has detrimental effects on health. The budding yeast Saccharomyces cerevisiae is an accepted cellular model iron metabolism humans primarily because degree conservation between pathways involved. Here we report systematic screen using deletion mutants to...
Zinc is an essential nutrient because it a required cofactor for many enzymes and transcription factors. To discover genes processes in yeast that are growth when zinc limiting, we used genome-wide functional profiling. Mixed pools of ∼4,600 deletion mutants were inoculated into zinc-replete zinc-limiting media. These cells grown several generations, the prevalence each mutant pool was then determined by microarray analysis. As result, identified more than 400 different optimal under...
Significance The growing use of lanthanides in various industries has increased the potential for human exposure to large concentrations these heavy metals throughout life cycle new technologies, requiring more detailed investigations into their toxicological properties. eukaryote model organism Saccharomyces cerevisiae is ideal apply functional toxicogenomics tools at system level and probe fundamental cellular functions disrupted by rare-earth metals. A comprehensive mechanistic assay was...
Benzene is a ubiquitous environmental contaminant and widely used in industry. Exposure to benzene causes number of serious health problems, including blood disorders leukemia. undergoes complex metabolism humans, making mechanistic determination toxicity difficult. We functional genomics approach identify the genes that modulate cellular three phenolic metabolites benzene, hydroquinone (HQ), catechol (CAT) 1,2,4-benzenetriol (BT), model eukaryote Saccharomyces cerevisiae. generate oxidative...
Background & AimsMulticopper ferroxidases (MCFs) facilitate intestinal iron absorption and systemic recycling, likely by a mechanism involving the oxidization of Fe2+ from exporter ferroportin 1 for delivery to circulating Fe3+ carrier transferrin. Hephaestin (HEPH), only MCF known be expressed in enterocytes, aids basolateral transfer dietary blood. Mice lacking HEPH whole body (Heph-/-) or intestine alone (Hephint/int) exhibit defects but still survive grow. Circulating ceruloplasmin (CP)...
Arsenic is a human toxin and carcinogen commonly found as contaminant in drinking water. Arsenite (AsIII) the most toxic inorganic form, but recent evidence indicates that metabolite monomethylarsonous acid (MMAIII) even more toxic. We have used chemical genomics approach to identify genes modulate cellular toxicity of MMAIII AsIII yeast Saccharomyces cerevisiae. Functional profiling using homozygous deletion mutants provided requirement highly conserved biological processes response against...
The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations neuronal expression can be observed even following single injection. To investigate the extent of these changes, medial striatum lumbar part spinal cord was monitored by cDNA microarray injection morphine. Using robust resistant linear regression (MM-estimator) with simultaneous prediction confidence intervals, we detected differentially...
Toxicogenomics, the genome-wide analysis of gene expression to study effect toxicants, has great potential for use in environmental toxicology. Applied standard test organisms, it possible applications aquatic toxicology as a sensitive monitoring tool detect presence contaminants while providing information on mechanisms action these pollutants. We describe complementary DNA (cDNA) microarray fathead minnow (Pimephales promelas) sentinel organism toxicology, better understand toxicity...
Ecotoxicogenomic approaches are emerging as alternative methods in environmental monitoring because they allow insight into pollutant modes of action and help assess the causal agents potential toxicity beyond traditional end points death, growth, reproduction. Gene expression analysis has shown particular promise for identifying gene biomarkers chemical exposure that can be further used to monitor specific exposures environment. We focused on development markers detect discriminate between...
Daphnia magna is a bioindicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of rely on acute and chronic toxicity that provide no insight into the cause toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to assessment. While these genomic methods providing important mechanistic toxicity, statistically robust prediction systems allow...
Exploratory outlier identification methods and confirmatory gene expression studies showed induction of the iron regulon in Saccharomyces cerevisiae lacking Mac1p, a copper-responsive transcription factor. The Aft1p/Aft2p binding motif was most discriminating between up- down-regulated genes, we identified new genes potentially regulated by Aft1p/Aft2p. In addition, multiple encoding proteins containing Fe-S clusters were suggesting metabolic reorganization to conserve mac1Delta. Null...
Abstract Background Iron-deficiency anemia is the most prevalent form of world-wide. The yeast Saccharomyces cerevisiae has been used as a model cellular iron deficiency, in part because many its pathways are conserved. To better understand how cells respond to changes availability, we profiled genome with parallel analysis homozygous deletion mutants identify essential components and processes required for optimal growth under iron-limited conditions. complement this analysis, compared...
Lanthanides are a series of elements essential to wide range applications, from clean energy production healthcare. Despite their presence in multiple products and technologies, toxicological characteristics have been only partly studied. Recently, our group has employed genomic approach extensively characterize the toxicity mechanisms lanthanides. Even though we identified substantially different behaviors for mid late lanthanides, profiles early lanthanides remained elusive. Here, overcome...
Exposure to organochlorinated pesticides such as dieldrin has been linked Parkinson's and Alzheimer's diseases, endocrine disruption, cancer, but the cellular molecular mechanisms of toxicity behind these effects remain largely unknown. Here we demonstrate, using a functional genomics approach in model eukaryote Saccharomyces cerevisiae, that alters leucine availability. This is supported by multiple lines congruent evidence: (1) mutants defective amino acid signaling or transport are...
Fundamental questions remain about the application of omics in environmental risk assessments, such as consistency data across laboratories. The objective present study was to determine congruence transcript 6 independent Male fathead minnows were exposed a measured concentration 15.8 ng/L 17α-ethinylestradiol (EE2) for 96 h. Livers divided equally and sent participating laboratories transcriptomic analysis using same minnow microarray. Each laboratory free apply bioinformatics pipelines its...
Abstract Organochlorine pesticides, once widely used, are extremely persistent and bio-accumulative in the environment. Epidemiological studies have implicated that environmental exposure to organochlorine pesticides including dieldrin is a risk factor for development of Parkinson’s disease. However, pertinent mechanisms action remain poorly understood. In this study, we carried out genome-wide (Brunello library, 19 114 genes, 76 411 sgRNAs) CRISPR/Cas9 screen human dopaminergic SH-SY5Y...
Mechanisms of gadolinium toxicity have been identified by multidimensional toxicogenomic profiling.
Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational environmental exposure to FA prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, lymphohematopoietic cancers, have been linked exposure, prompting designation of as human carcinogen by U.S. international scientific entities. Although the mechanism(s) toxicity well studied, additional insight needed in regard genetic requirements for tolerance. In...
Europium is a lanthanide metal that highly valued in optoelectronics. Even though europium used many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses different systems or bioaccumulation vivo. This paper describes genome-wide toxicogenomic study of Saccharomyces cerevisiae, which shares biological functions humans. By using multidimensional approach and functional network analyses, we have identified...
Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series be divided into three parts, namely early, mid, and late lanthanides, based on interactions with systems. In particular, demonstrate distinct, but poorly understood activity. current study, we employed genome-wide functional screening to help understand effects of exposure Yb(III) Lu(III), which were selected as...
Exposure to toxaphene, an environmentally persistent mixture of chlorinated terpenes previously utilized as insecticide, has been associated with various cancers and diseases such amyotrophic lateral sclerosis. Nevertheless, the cellular molecular mechanisms responsible for these toxic effects have not established. In this study, we used a functional approach in model eukaryote Saccharomyces cerevisiae demonstrate that toxaphene affects yeast mutants defective (1) processes transcription...
The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome (PI)-refractory multiple myeloma, nelfinavir-based therapy resulted 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option setting. mechanism of action implies it interferes fundamental aspects cancer cell biology. We combined proteome-wide affinity-purification nelfinavir-interacting...
Dimethyl sulfoxide (DMSO) is frequently utilized as a solvent in toxicological and pharmaceutical investigations. It therefore important to establish the cellular molecular targets of DMSO order differentiate its intrinsic effects from those elicited by compound interest. We performed genome-wide functional screen Saccharomyces cerevisiae identify deletion mutants exhibiting sensitivity 1% DMSO, concentration standard yeast chemical profiling studies. report that defective Golgi/ER transport...