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.
PhD - Washington State University
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.
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. Fert and Steril (2010) 94:2626-2630. (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. Fert and Steril (2010) 94:2088-2095. (http://www.ncbi.nlm.nih.gov/pubmed/20171613).
Ding J, Swain JE, Smith GD. Aurora kinase-a regulates microtubule organizing center (MTOC) localization, chromosome dynamics and histone-H3 phosphorylation in mouse oocytes. Mol Reprod Dev (2011), 78:80-90.
Bormann CL, Padmanabhan V, Smith GD, Lee TM. Prenatal testosterone and dihydrotestosterone exposure alters ram testes development. Reproduction (2011) 142:167-173.
Swain JE and Smith GD. Advances in IVF culture platforms: Novel approaches to improve preimplantation embryo development through modification of microenvironments Hum Reprod Update (2011) 17: 541-557.