Environmental and developmental toxicology

Francis is an environmental toxicologist whose work focuses on the irreversible effects of pesticides. One focus of her research is on alterations in gene expression following exposure to environmental agents (broadly defined). By using chemicals that affect gene expression (e.g., retinoic acid) and cause malformations in experimental animals, she attempts both to identify mechanisms by which developmental toxicants cause malformations, and to identify genes acting in normal development.

Francis also has a strong interest in pesticide in toxicology, and especially their irreversible effects. Such studies often intersect the developmental studies. For example, the herbicide nitrofen (2,4-dichlorophenyl 4'-nitrophenyl ether) causes a unique constellation of defects in rodents that is highly suggestive of perturbed gene expression as a primary mechanism.. Nitrofen causes malformations of the kidneys, heart, diaphragm, and Harderian glands if administered to mice on gestational day (GD) 8 development. It does not cause limb malformations, even though our experience shows that most teratogens that cause cell death or decrease cell proliferation will cause limb malformations on GD 8.

Another example is the delayed paralysis that follows exposure to some organophosphorus esters (OPs). In humans, both adults and children can be affected, although children seem to be less sensitive. In chickens, only mature fowl become paralyzed -- chicks do not. However, when chick embryos or very young chicks are exposed to such OPs, long-lastin functional deficits result. In some cases, birds remained abnormal even as adults. Neither the mechanism for the adult paralysis nor for the develmental effects is known.

Additional pesticide studies include comparison of structure-activity relationships among nitrofen analogs and examination of the possibility that pesticides cause endocrine disruption, either by altering estrogen metabolism (DDT) or thyroid function (nitrofen) in developing fetuses and their dams.

Finally, Francis remains interested in the ecological effects of pesticide use, and uses the Metcalf microcosm to investigate these.