Areas of Interest
Research in this laboratory focuses on regulation of mammalian gamete and embryo development and function. Specifically we are investigating:
- intracellular regulation of oocyte chromatin remodeling and segregation during meiosis,
- factors and forces influencing sperm function,
- 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 condensation, 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, as well as elucidate intracellular regulatory pathways of normal development and differentiation.
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.
Acevedo NA, Ding J, Dunn R, Smith GD. Insulin signaling in mammalian oocytes. Biol Reprod (2007) 77:872-879.
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) 14: 291-299.
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) 90:1396-1404.
Schulte R, Keller LM, Hiner MR, Ohl DA, Smith GD. Temporal decreases in sperm motility: which patients should have motility checked at both one and two hours after collection? J of Andrology (2008) 29:558–563.
Villa-Diaz LG, Pacut C, Slawny NA, Ding J, O’Shea KS, Smith GD. Analysis of the factors that limit the ability of feeder-cells to maintain the undifferentiated state of human embryonic stem cells. Stem Cell and Development (2009) 18:641-651.
Villa-Diaz, LG, Torisawa Y, Uchida T, Ding J, Nogueira-de-Souza NC, O’Shea KS, Takayama S, Smith GD. Microfluidic culture of single human embryonic stem cell colonies. Lab on a Chip (2009) 9:1749 -1755.
Motta EL, Smith GD, Serafini PC, Coslovsky M, Hassun P, Rocha A, Yadid I. Human choriogonadotropin prior to controlled ovarian stimulation and in vitro fertilization improves embryo development, implantation, and pregnancy rates. J of Assist Reprod and Genetics (2009) 26:305-311.
Heo YS, Cabrera LM, Bormann C, Shah CT, Takayama S, Smith GD. Dynamic microfunnel culture enhances embryo development and pregnancy rates. Human Reproduction (2010) 25:613-622.
Villa-Diaz LG, Nandivada H, Ding J, O’Shea, KS, Lahann J, Smith GD. Synthetic polymeric coatings for long-term maintenance of undifferentiated human embryonic stem cell growth. Nature Biotech (2010) 28:581-583 (http://www.ncbi.nlm.nih.gov/pubmed/20512122).
Jackson RE, Bormann CL, Hassun PA, Rocha AM, Motta ELA, Serafini PC, Smith GD. Effects of semen storage and separation techniques on sperm DNA fragmentation. Fertility and Sterility (2010) in press (http://www.ncbi.nlm.nih.gov/pubmed/20542505).
Smith GD, Serafini PC, Fioravanti J, Yadid I, Coslovsky M, Hassun P, Alegretti JR, Motta EL. Prospective randomized comparison of human oocyte cryopreservation with slow-rate freezing and vitrification. Fertility and Sterility (2010) in press (http://www.ncbi.nlm.nih.gov/pubmed/20171613).
PhD - Washing State Uinversity