Perinatal toxicology is the focus of this laboratory. How viruses, metals, anti-HIV therapy, and vitamins (A, B12, C and E) affect normal development of the embryo/ fetus are being investigated. In particular, the role of the placenta as the anchor, controller, and conduit during pregnancy as well as a site for toxic action is examined.

      HIV. Why do only 25-40% of the babies of HIV positive mothers become infected? Why not all the babies? What controls infectivity of the fetus in utero? These are questions being explored in patients who are pregnant and HIV positive. In vitro models of human placenta are used to study how the placenta may modulate HIV infection in utero. Certain strains of HIV-1 can selectively infect the human placenta, while others do not. Molecular technics are being used PCR, ISPCR to determine which cells are being infected. With these models we can test how anti-HIV therapies may best prevent the vertical transmission of HIV as well as produce toxicity in the human placenta. Further studies of the environmental interactions of ethanol exposure and HIV infection are in progress.

      Placental Toxicology. Cadmium can be a placental toxin in rodents by producing fetal death and placental necrosis. Using an in vitro dually perfused human placenta model showed that cadmium also produced necrosis. The response of the cell to cadmium toxicity may be regulated by metallothionein and calmodulin. Different isoforms of metallothionein are being identified via cDNA isolation and in situ hybridization for determination of metallothionein distribution and inducibility in placentae from women exposed during pregnancy to environmental metals

      Implantation Biology. Pregnancy loss due to implantation failures is being examined using an in vitro model consisting of both human trophoblast and endometrium to study the biology of attachment and invasion as well as the influence of hormones, immune factors, and xenobiotics.

Miller MW, Church CC, Miller RK, Edwards MJ. Fetal thermal dose considerations during the obstetrician’s watch: Implications for the pediatrician’s observations. Birth Defects Res C Embryo Today. 2007 Sep;81(3):135-143. Review.

Moore JK, Miller RK. The cyclin-dependent kinase Cdc28p regulates multiple aspects of Kar9p function in yeast. Mol Biol Cell. 2007 Apr;18(4):1187-1202.

Miller RK, D’Silva S, Moore JK, Goodson HV. The CLIP-170 orthologue Bik1p and positioning the mitotic spindle in yeast. Curr Top Dev Biol. 2006;76:49-87. Review.

Dertinger SD, Miller RK, Brewer K, Smudzin T, Torous DK, Roberts DJ, Avlasevich SL, Bryce SM, Sugunan S, Chen Y. Automated human blood micronucleated reticulocyte measurements for rapid assessment of chromosomal damage. Mutat Res. 2007 Jan 10;626(1-2):111-119.

Moore JK, D’Silva S, Miller RK. The CLIP-170 homologue Bik1p promotes the phosphorylation and asymmetric localization of Kar9p. Mol Biol Cell. 2006 Jan;17(1):178-191.

Miller RK, Genbacev O, Turner MA, Aplin JD, Caniggia I, Huppertz B. 2005. Human placental explants in culture: approaches and assessments. Placenta. Jul;26(6):439-448. Review.

Dertinger SD, Camphausen K, Macgregor JT, Bishop ME, Torous DK, Avlasevich S, Cairns S, Tometsko CR, Menard C, Muanza T, Chen Y, Miller RK, Cederbrant K, Sandelin K, Ponten I, and Bolcsfoldi G. 2004. Three-color labeling method for flow cytometric measurement of cytogenetic damage in rodent and human blood. Environ Mol Mutagen. 44(5):427-435.

Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, and Guzick DS. 2004. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Fertil Steril. Aug;82(2):421-429.

Dertinger SD, Chen Y, Miller RK, Brewer KJ, Smudzin T, Torous DK, Hall NE, Olvany KA, Murante FG, and Tometsko CR. 2003. Micronucleated CD71-positive reticulocytes: a blood-based endpoint of cytogenetic damage in humans. Mutat Res. 2003 Dec 9;542(1-2):77-87.

Miller RK, Mace K, Polliotti B, DeRita R, Hall W, and Treacy G. 2003. Marginal transfer of ReoPro (Abciximab) compared with immunoglobulin G (F105), inulin and water in the perfused human placenta in vitro. Placenta. Aug;24(7):727-738.

Polliotti BM, Fry AG, Saller DN, Mooney RA, Cox C, and Miller RK. 2003. Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe, early-onset preeclampsia. Obstet Gynecol. Jun;101(6):1266-1274