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Research Summary
The overall focus of my laboratory is to investigate how environmental agents (drugs, pollutants, industrial byproducts, pesticides, etc) induce congenital malformations, particularly ones that involve the nervous and cardiovascular systems. Although these systems are anatomically distinct, they possess biological, biochemical and molecular similarities that govern their development. Using murine models, microarray technology and standardized immunohistochemistry techniques we are trying to identify molecular and/or biochemical pathways that are altered by various teratogenic insults. One current project is to determine whether agents (drugs or environmental pollutants) that induce congenital neural and/or cardiac malformations, alter the function, expression or distribution of the NMDA (N-methyl-d-aspartate) receptors. These receptors are known to regulate developmentally important biochemical and cellular events and if they are expressed at the wrong place or time the developmental progression of the embryo may be altered ultimately leading to a congenital malformation. Another project involves determining whether homocysteine, an independent risk factor for vascular disease, is associated with congenital malformations. Using animals models along with molecular and biochemical techniques we are investigating how moderately high plasma levels of this simple amino acid leads to alterations in gene expression, protein distribution, and cellular events (such as intracellular calcium levels in specific cell types) disrupt normal embryonic development. Therefore, although the agents are varied and the techniques diverse the focus of my laboratory remains focused on trying to understand the biochemical and molecular events that when altered lead to congenital defects, particularly ones that influence the developing nervous and cardiovascular systems. |
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Research Publications
Rosenquist T, Bennett GD, Brauer P, Stewart M, Chadoin T, Finnell R. 2007. Microarray ananlysis of homocysteine-responsive genes in cardiac neural crest cells in vitro. Dev Dyn 236(4):1044-54
Bennett GD, Gelineau-van Waes J, Moser K, Chaudoin T, Starr L, Rosenquist TH. 2006 Failure of Homocysteine to Induce Neural Tube Defects in a Mouse Model. Birth Defects Research Part B: Developmental and Reproductive Toxicology 77:89-94
Bennett GD, Moser K, Chaudoin T, Rosenquist TH. 2006. The Expression of the NR1-Subunit of the NMDA Receptor during Mouse Development. Reproductive Toxicology 22:536-541
Gefridies LA, Bennett GD, Finnell RH. 2002. The effects of folate supplementation on the risk of induced and spontaneous neural tube defects in Splotch mice. Teratology 65(2) 63-9
Isoherranen N, White HS, Finnell RH, Yagen B, Woodhead JH, Bennett GD, Wilcox KS, Barton ME, Bialer M. 2002. Anticonvulsant Profile and Teratogenicity of N-methyl- tetramethylcyclopropyl carboxamide: A New Antiepileptic drug. Epilepsia ()
Spiegelstein O, Yagen B, Bennett GD, Finnell RH, Blotnik S, Bialer M. 2000. Stereoselective Pharmacokinetic Analysis of Valnoctamide, a CNS-active chiral Amide Analogue of Valproic Acid in Dogs, Rats and Mice. Ther Drug Monitor 22:574-581 Piedrahita JA, Oetama B, Bennett GD, van Waes J, Lacey SW, Kamen BA, Richardson J, Lark RH, Finnell RH. 1999. Mice lacking the folic acid binding protein folbp-1 are defective in early development. Nature Genetics 23:228-232 |
