Project Leader, David J. Waxman (Boston University, Department of Biology)
Studying exposure to xenoestrogens and other endocrine-disrupting chemicals associated with a variety of developmental and reproductive abnormalities.
Environmental exposure to foreign chemicals with estrogenic and other endocrine activities is widespread and is proposed to impact adversely on the health of humans, fish and wildlife. Exposure to xenoestrogens and other endocrine-disrupting chemicals has been associated with a variety of developmental and reproductive abnormalities, with observed toxicities ranging from infertility in rodents and domestic animals, to abnormal reproductive behavior and development in birds, to decreased hormone levels and early mortality in fish. This project investigates the actions of environmental chemicals that exert reproductive toxicities, with special emphasis on environmental estrogens and anti-androgens that induce gonadal toxicities in exposed mammals. A major goal of these studies is to elucidate the role of nuclear receptors and other xenochemical-activated transcription factors, such as aryl hydrocarbon (Ah) receptor, and their interactions with nuclear receptors that mediate environmental chemical-induced reproductive toxicities. A second major goal is to elucidate the action of environmental chemicals that exert endocrine disruptor activity indirectly, through the actions of protein kinases on nuclear receptor-dependent transcription, as exemplified by the action of methoxyacetic acid, the active metabolite of the industrial solvent ethylene glycol monomethyl ether. A third goal is to apply computational methods developed by the Bioinformatics Core to further our understanding of the receptor-based and metabolic actions of endocrine-active environmental chemicals through the study of nuclear receptors and cytochromes P450 that, respectively, interact with and metabolize these chemicals. Together, these studies will enhance our understanding of the nuclear receptor-dependent mechanisms through which endocrine-active environmental chemicals induce gonadal toxicities, and may, ultimately, help to identify strategies to improve the detection and prevention of adverse effects in exposed individuals.
Principal Investigator: David Waxman
websites:
http://blogs.bu.edu/djwweb
http://www.bu.edu/biology/people/faculty/waxman/
