A5025119335- Toxic Organic Pollutants Impact
- Carcinogens and Genotoxicity Assessment
- Effects and risks of endocrine disrupting chemicals
- Estrogen and related hormone effects
- Hematopoietic Stem Cell Transplantation
- Pharmacogenetics and Drug Metabolism
- Immunotoxicology and immune responses
- Tea Polyphenols and Effects
- Drug Transport and Resistance Mechanisms
- T-cell and B-cell Immunology
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Heavy Metal Exposure and Toxicity
- Epigenetics and DNA Methylation
- Heat shock proteins research
- Selenium in Biological Systems
- Pesticide Exposure and Toxicity
- Free Radicals and Antioxidants
- Adipose Tissue and Metabolism
- Microbial bioremediation and biosurfactants
- Cancer, Hypoxia, and Metabolism
- Porphyrin Metabolism and Disorders
- Exercise and Physiological Responses
- Meat and Animal Product Quality
- Mass Spectrometry Techniques and Applications
University of Rochester
2006-2023
University of Rochester Medical Center
2005-2018
Alkermes (United States)
2005
The Barbara Ann Karmanos Cancer Institute
1999
Wayne State University
1999
Environmental Protection Agency
1995
Research Triangle Park Foundation
1982-1995
Stanford University
1990
Vanderbilt University
1979-1981
2,3,7,8-Tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) is a widespread environmental pollutant with many toxic effects, including endocrine disruption, reproductive dysfunction, immunotoxicity, liver damage, and cancer. These are mediated by TCDD binding to activating the aryl hydrocarbon receptor (AhR), basic helix-loop-helix transcription factor. In this regard, targeting AhR using novel small molecule inhibitors an attractive strategy for development of potential preventive agents. study,...
The strains of mice, C57BL/6J, DBA/2J, and B6D2F1/J, have been used as models to study the mechanism action 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). distribution, excretion, metabolism this compound was studied in male B6D2F1/J mice following intraperitoneal administration radiolabeled TCDD at a dose 10 micrograms/kg. In all strains, liver adipose tissue were major sites for accumulation 3H-TCDD, with more 3H-TCDD being distributed livers C57BL/6J compared DBA/2J strain. While feces route...
Diseases such as chronic obstructive pulmonary disease and lung cancer caused by cigarette smoke affect millions of people worldwide. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that influences responses to certain environmental pollutants tobacco smoke. However, the physiological function(s) AhR unknown. Herein we propose physiologic role limit inflammation. We show fibroblasts from AhR–/– mice produce heightened inflammatory response smoke, typified...
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to mediate the toxic effects of numerous environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs). Historically, binding PAHs AhR and events leading generation DNA adducts have been associated with chemical carcinogenesis. Previous investigations implicated green tea (GT) as affording protection against PAH-induced cancers in animal models. Investigations our laboratory demonstrated that...
Abstract Estrogens affect the development, maturation, and function of multiple organ systems, including immune system. One main targets estrogens in system is thymus, which undergoes atrophy phenotypic alterations when exposed to elevated levels estrogen. To determine how influence thymus T cell estrogen receptor α (ERα) knockout (ERKO) mice were examined. ERKO have significantly smaller thymi than their wild-type (WT) littermates. Construction ER radiation bone marrow chimeras indicated...
(−)-Epigallocatechin-3-gallate (EGCG), a major component of green tea, protects against certain types cancers, although the mechanism has not yet been determined. It was previously demonstrated that EGCG blocks aryl hydrocarbon receptor (AhR)-mediated transcription induced by potent carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Unlike other AhR antagonists directly bind to AhR, inhibits AhR-mediated binding hsp90. We hypothesize exerts anti-AhR and anticancer effects acting as an...
The presence and properties of the Ah receptor were examined in guinea pig, rat, hamster, monkey, three different strains mice. These species have demonstrated differences sensitivity variability response to 2,3,7,8-tetrachlorodibenzo-p-dioxin related compounds. All examined, with exception DBA/2J mice, possess similar amounts binding protein high affinity for hepatic tissue. Numerous dibenzo-p-dioxin congeners polycyclic aromatic hydrocarbons a rank order ability bind molecules from these...
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related congeners affect the immune system, causing immunosuppression thymic atrophy in a variety of animal species. TCDD is believed to exert its effects primarily through ligand-activated transcription factor, aryl hydrocarbon receptor (AhR). Although AhR found at high levels both thymocytes stroma, it uncertain which cells activating cause alterations thymus. Some investigators have suggested that stromal elements, epithelial cells, within...
The Ah receptor in rat hepatic cytosol was transformed to a DNA-binding form by incubation vitro with the ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin. covalently cross-linked bromodeoxyuridine-substituted DNA recognition motif exposure ultraviolet irradiation. Analyses of protein-DNA complexes gel electrophoresis and autoradiography imply that liganded is composed two protein components, whose molecular masses are about 110 100 kDa. Protease digestion studies suggest components have different...
Perinatal exposure of experimental animals to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads thymic atrophy and a suppression cell-mediated immunity that is more severe persistent than caused by adult exposure, suggesting events involved in maturation immune system are particularly sensitive TCDD. We report here perinatal TCDD produces an alteration lymphocyte stem cell population fetus neonate, as evidenced significant reduction cell-specific enzyme terminal...
The aryl hydrocarbon receptor (AhR) belongs to the basic helix-loop-helix family of DNA-binding proteins that play a role in toxicity and carcinogenicity certain chemicals. most potent ligand AhR known is 2,3,7,8-tetracholorodibenzo-p-dioxin. We previously reported tetrachlorodibenzo-p-dioxin-induced alterations numbers function hematopoietic stem cells (HSCs). To better understand possible hematopoiesis, studies were undertaken young adult null-allele (KO) mice. These mice have enlarged...
It is well established that hypoxia contributes to tumor progression in a inducible factor-2α (HIF-2α)-dependent manner renal cell carcinoma (RCC), yet the role of long noncoding RNAs (LncRNAs) involved hypoxia-mediated RCC remains unclear. Here we demonstrate LncRNA-SARCC (Suppressing Androgen Receptor Renal Cell Carcinoma) differentially regulated by von Hippel-Lindau (VHL)-dependent both culture and clinical specimens. can suppress hypoxic cycle VHL-mutant cells while derepress it...