Wei Cui

Wei Cui, Ph.D.

Extension Assistant Professor

Principal Investigator

he, him, his

Office: 

S521 LSL

Mailing address: 

University of Massachusetts
240 Thatcher Road
Amherst, MA 01003 

Office phone: 

413-545-0673

 
Ph.D.: Shandong Agricultural University, China, 2013
Postdoctoral Training
University of Kansas Medical Center, 2013-2014 
University of Massachusetts Amherst, 2014-2017
 
Honors:
The Lalor Foundation Postdoctoral Fellowship, 2015
 

 
Classes: 

ANIMLSCI 521- Physiology of Reproduction Laboratory
ANIMLSCI 697J - Cells, Genes and Development
ANIMLSCI 795A - Journal Club in Cells, Genes and Development

Research Interests

 
Research in my laboratory aims at: 1) understanding the cellular and molecular mechanisms underlying mammalian oocyte meiosis, activation, and aging; 2) discovering novel genes, factors, and signaling pathways that are functionally required during mammalian preimplantation embryo development; 3) creating animal models of human genetic diseases using knock-out, knock-in, and transgenesis strategies.

Mammalian oocyte meiosis, activation, and aging

Mammalian oocytes enter meiosis during fetal development, and arrest at diplotene stage of meiotic prophase I - also called germinal vesicle (GV) stage, until puberty. During this prolonged arrest, oocytes grow, differentiate and stockpile maternal components. Following puberty, oocytes resume meiosis under the action of gonadotropin hormones. For most mammals, after going through germinal vesicle breakdown (GVBD), metaphase I (MI), as well as anaphase/telophase I, oocyte extrudes the first polar body and reaches metaphase II (MII). The matured MII oocyte is then ovulated and is ready for fertilization. In some cases, if fertilization or parthenogenetic activation cannot take place right away, oocyte will arrest at MII stage but postovulatory aging then occurs. However, in some species (rat, hamster, some mouse strains, and some patients), spontaneous exit from MII arrest - also named spontaneous activation, can occur quickly in vitro and/or in vivo. A tremendous investment and complicated network (cell-cell interactions, hormones, second messenger molecules, cell cycle regulators, organelle and cytoskeletal systems, transcription and translation factors, ion channels, etc.) has been generated by the body to ensure a high quality oocyte, however, this machinery is also being challenged by environmental exposures, diet, lifestyle, and age. Thus, only understanding the full developmental network, specifically under current challenging situations, can guide our management of human reproduction, including assisted reproductive technology (ART).  

Mammalian preimplantation embryo development

Preimplantation development refers to the period from fertilization to implantation, during which the fertilized oocyte progresses through a number of cleavage divisions and major transcriptional and morphogenetic events that lead to the first cell-fate decision (inner cell mass [ICM] and trophectoderm [TE]) and development into a blastocyst capable of implantation. During this brief but dynamic time window, several events occur, which include: 1) maternal-to-zygotic transition (MZT), namely, degradation of maternal mRNAs and replacement with zygotic transcripts; 2) embryo compaction and polarization, which initiate during the 8-cell stage in mouse embryos; 3) blastomere allocation and ICM/TE separation, which is the very first cell fate determination of our life. Previous microarray and current RNA-seq both confirmed more than 10,000 genes expressed during this period; however, for most of these genes, we do not know their function. More importantly, this time window is right clinically relevant: after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), human preimplantation embryos need to be cultured in a dish and incubator for several days, then transferred into mother’s uterus. Thus, understanding the role of each expressed gene and what happens during the culture is an essential next step for elucidating developmental networks at play and improving human assisted reproduction.

Animal model generation

There are multiple strategies to create genetically modified animal models. The earliest one is microinjection of foreign DNA into pronucleus to make transgenic animals. This method is straightforward (direct injection into 1-cell embryo); however, integration locus and copy numbers are random. When gene targeting technology is available, we can accurately modify specific locus of interest; but, due to the very low rate of homologous recombination, we have to rely on an excess of somatic cells or stem cells cultured in vitro, then, positive cells are selected to perform somatic cell nuclear transfer (SCNT) to get cloned animals, or through stem cell blastocoel injection to make chimera. In other words, these methods are effective but indirect and not straightforward, thus time consuming. When engineered nucleases (ZFN, TALEN, CRISPR/Cas9) are utilized, things become easier. These nucleases can accurately find precise locus of interest with high efficiency, so we can do direct microinjection into 1-cell embryos for directed gene editing. Compared with ZFN and TALEN, CRISPR/Cas9 system is easier to design, more flexible and cost effective. Currently, we are taking advantage of CRISPR/Cas9 system to perform gene editing. In addition to knock-out, knock-in and transgenic models, my laboratory also works on generation of patient-derived xenograft (PDX) cancer models.
 

Lab Personnel

Name Email Phone Office
Houh, Angela
Undergraduate Student
ahouh [at] umass.edu 413-545-0673 LSL S560F
Miao, Xiaosu (Sue)
Graduate Student - ABBS
xiaosumiao [at] umass.edu 413-545-0673 LSL S560F
Sun, Tieqi
Undergraduate Student
tieqisun [at] umass.edu 413-545-0673 LSL S560F

Publications

Wu, X., Liu, Y., Wang, W., Crimmings, K., Williams, A., Mager, J., & Cui, W.. (2022). Early embryonic lethality of mice lacking POLD2. Molecular Reproduction and Development, 90, 98–108. doi:10.1002/mrd.23663
Cui, W. (2021). Oocyte Spontaneous Activation: An Overlooked Cellular Event That Impairs Female Fertility in Mammals. Front Cell Dev Biol, 9, 648057. presented at the 2021. doi:10.3389/fcell.2021.648057
Hawkins, J., Miao, X., Cui, W., & Sun, Y.. (2021). Biophysical optimization of preimplantation embryo culture: what mechanics can offer ART. Mol Hum Reprod, 27(1). presented at the 2021 01 22. doi:10.1093/molehr/gaaa087
Su, J., Miao, X., Archambault, D., Mager, J., & Cui, W.. (2021). ZC3H4-a novel CCCH-type zinc finger protein-is essential for early embryogenesis in mice†.. Biol Reprod, 104(2), 325-335. presented at the 2021 02 11. doi:10.1093/biolre/ioaa215
Cui, W. (2020). SOHLHs are essential for fertility regardless of gender or population. Fertil Steril, 114(2), 283-284. presented at the 2020 08. doi:10.1016/j.fertnstert.2020.06.010
Miao, X., Sun, T., Golan, M., Mager, J., & Cui, W.. (2020). Loss of POLR1D results in embryonic lethality prior to blastocyst formation in mice. Molecular Reproduction and Development, 87, 1152–1158. doi:10.1002/mrd.23427
Cui, W., Cheong, A., Wang, Y., Tsuchida, Y., Liu, Y., Tremblay, K. D., & Mager, J.. (2020). MCRS1 is essential for epiblast development during early mouse embryogenesis. Reproduction, 159(1), 1-13. presented at the 2020 01. doi:10.1530/REP-19-0334
Zhang, Y., Qu, P., Ma, X., Qiao, F., Ma, Y., Qing, S., et al.. (2018). Tauroursodeoxycholic acid (TUDCA) alleviates endoplasmic reticulum stress of nuclear donor cells under serum starvation. PLoS One, 13(5), e0196785. presented at the 2018. doi:10.1371/journal.pone.0196785
Kubota, K., Cui, W., Dhakal, P., Wolfe, M. W., Rumi, M. A. Karim, Vivian, J. L., et al.. (2016). Rethinking progesterone regulation of female reproductive cyclicity. Proceedings of the National Academy of Sciences, 113, 4212–4217. presented at the mar. Retrieved from https://doi.org/10.1073/pnas.1601825113