Research in this laboratory focuses on regulation of mammalian gamete and embryo development and function. Specifically we are investigating:

1) intracellular regulation of oocyte chromatin remodeling and segregation during meiosis,
2) factors and forces influencing sperm function,
3) microenvironment and its influence on preimplantation embryos and human embryos stem cell (hESC) development.

Studies in this laboratory range from very basic in nature to translational research aimed at introducing new or improving existing means of fertility preservation or infertility treatment.
Investigations on oocyte meiosis within our lab focus on interplay of kinases (cdc2-kinase, MAP-kinases, glycogen synthase kinase-3, and aurora kinases) and phosphatases (PPP1 and PPP2A) in regulation of nuclear membrane integrity, spindle formation and function, and chromatin condenstation, separation, and congression failure. Thus, molecular, cellular, and functional studies aid in elucidating roles of reversible phosphorylation in nuclear and cytoplasmic oocyte maturation and subsequent embryonic developmental competence.

Gamete cryopreservation for preservation of fertility post-cancer therapy is of increasing importance. Practical studies on ultra-rapid freezing of semen, vitrification of oocytes, and slow-rate cryopreservation of ovarian tissue are examples of ongoing projects. These technical studies are coupled with cellular assessments to determine cryo-damage at the structural, functional (sperm motility; oocyte meiotic spindle) and developmental (in vitro folliculogenesis and preimplantation embryogenesis) levels.

Lastly, in collaboration with laboratories in BioMedical Engineering, Chemical Engineering, and Chemistry we investigate importance of microenvironment on oocyte, preimplantation embryo, and hESC development. These studies use microfluidics, hydrogels, capillary electrophoresis and nano-sensors to modify and analyze cells in culture in hopes of closing gaps between cellular growth and development in vivo and that which occurs in culture.

Representative Publications:
Wang X, Liu XT, Dunn RL, Ohl DA, Smith GD. Glycogen synthase kinase-3 regulates oocyte homologue segregation. Mol Reprod Dev (2003) 64:96-105.

Swain JE, Wang X, Saunders TL, Dunn R, Smith GD. Specific inhibition of mouse oocyte nuclear protein phosphatase-1 stimulates germinal vesicle breakdown. Mol Reprod Dev (2003) 65:96-103.

Cho B, Schuster T, Zhu X, Chang D, Smith GD, Takayama S. Passively driven integrated microfluidic system for separation of motile sperm. Anal Chem (2003) 75:1671-1675.

Swain JE and Smith GD. Direct effects of leptin on mouse folliculogenesis, oocyte maturation, fertilization, and preimplantation embryo development. Biol Reprod (2004) 71:1446-1452.

Suh RS, Phadke N, Ohl DA, Takayama S, Smith GD. In vitro fertilization within microchannels requires lower total numbers and lower concentrations of spermatozoa. Human Reprod (2006) 21: 477-483.

Kwok R, Liu XT, Smith GD. Distributions of co-activators CBP and p300 during mouse oocyte and embryo development. Mol Reprod Dev (2006) 73:885-894.

Acevedo N, Wang X, Dunn RL, Smith GD. Glycogen synthase kinase 3 regulation of chromatin segregation and cytokinesis in mouse preimplantation embryos. Mol Reprod Dev (2007) 74:178-188.

Swain JE, Ding J, Brautigan DL, Villa-Moruzzi E, Smith GD. Proper Chromatin condensation and maintenance of histone-H3 phosphorylation during mouse oocyte meiosis requires regulation of protein phosphatase activity. Biol Reprod (2007) 76:628-638.

Heo YS, Cabrera LM, Smith GD, Takayama S. Characterization and resolution of evaporation-mediated osmolality shifts that constrain microfluidic cell culture in poly(dimethylsiloxane) devices. Analytical Chem (2007) 79:1126-1134.

Acevedo NA, Ding J, Dunn R, Smith GD. Insulin signaling in mammalian oocytes. Biol Reprod (2007) 77(5):872-879.

Smith GD and Takayama S. Gamete and embryo isolation and culture with microfluidics. Theriogenology (2007) 68:S190-S195.

Swain JE, Ding J, Wu J, Smith GD. Regulation of spindle and chromatin dynamics during early and late stages of oocyte maturation by aurora kinases. Mol Human Reprod (2008) in press.

Gomes C, Silva C, Acevedo NA, Serafini P, Baracat E, Smith GD. Influence of vitrification on mouse metaphase II oocyte spindle dynamics and chromatin alignment. Fert and Steril (2008) in press.

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