|Life Sciences Building Rutgers University 145 Bevier Rd Piscataway, NJ, 08854|
|Understanding the molecular mechanisms that lead to aneuploidy in female gametes|
Haploid gametes (sperm and eggs) are generated by meiosis and are essential for sexual reproduction. In females, meiosis is highly error-prone as ~5-20% of a young, healthy woman’s eggs contain an abnormal number of chromosomes (aneuploid). Aneuploidy is the leading cause of infertility, miscarriage and, in the case of live birth, developmental disorders such as Down Syndrome. Little is known, however, about how meiosis in females is regulated and why it is so prone to chromosome segregation mistakes. Research in our group uses the mouse oocyte model to understand how signal transduction networks, specifically at the level of protein kinases and protein phosphatases, regulate female meiosis.
Nguyen AL, Drutovic D, Vazquez B, El Yakoubi W, Gentilello AS, Malumbres M, Solc P, Schindler K. Genetic interactions among the three Aurora kinases reveal new functions in mammalian female meiosis. Current Biology. In press.
Nguyen AL, Marin D, Scott R, Schindler K. (2018). A method to determine human gene function in meiosis using mouse oocytes. Journal of Visualized Experiments. (134), e57442, doi:10.3791/57442.
Balboula AZ, Blengini C, Gentilello AS, Takahasi M, Schindler K. (2017). Maternal RNA regulates Aurora C kinase during mouse oocyte maturation in a translation-independent fashion. Biology of Reproduction. 96(6): 1197-1209.
Quartuccio SM, Dipali SS, Schindler K. 2017. Haspin inhibition reveals functional differences of interchromatid axis-localized AURKB and AURKC. Molecular Biology of the Cell. doi: 10.1091/mbc.E16-12-0850. Epub ahead of print.
Nguyen AL, Marin D, Zhou A, Smoak EM, Gentilello AS, Cao Z, Fedick A, Wang Y, Taylor D, Scott Jr. RT, Xing J, Treff N, Schindler K. 2017. Identification and characterization of Aurora Kinase B and C variants associated with maternal aneuploidy. Molecular Human Reproduction. 23(6): 406-16.
Nguyen AL and Schindler K. 2017. Specialize and divide (twice): Functions of 3 Aurora kinase homologs in mammalian oocyte meiotic maturation. Trends in Genetics. 33(5): 349-63.
Radford SJ, Nguyen AL, Schindler K, McKim KS. 2017. The chromosomal basis of meiotic acentrosomal spindle assembly and function in oocytes. Chromosoma. 126(3): 351-64.
Ohring J and Schindler K. A Scrambled Mess. The Scientist. May 2016.
Balboula AZ, Nguyen AL, Gentilello AS, Quartuccio SM, Drutovic D, Solc P, Schindler K. 2016. Haspin kinase regulates microtubule-organizing center clustering and stability through Aurora kinase C in mouse oocytes. Journal of Cell Science. 129(19): 3648-60.
Fellmeth JE, Ghanaim ES, Schindler K. 2016. Characterization of macrozoospermia-associated AURKC mutations in a mammalian meiotic system. Human Molecular Genetics. 25(13): 2698-711.
Quartuccio SM and Schindler K. 2015. Functions of Aurora kinase C in meiosis and cancer. Frontiers in Cell and Developmental Biology. 3: 50.
Fellmeth JE, Gordon D, Robins CE, Scott RT, Treff NR, Schindler K. 2015. Expression and characterization of three Aurora kinase C splice variants found in human oocytes. Molecular Human Reproduction. 21(8): 633-44.
Balboula AZ, Stein P, Schultz RM, Schindler K. 2015. RBBP4 regulates histone deacetylation and bipolar spindle assembly during oocyte maturation in the mouse. Biology of Reproduction. 92(4): 105, 1-12.
Nguyen AL, Gentilello AS, Balboula AZ, Shrivastava V, Ohring J, Schindler K. 2014. Phosphorylation of threonine 3 on histone 3 by Haspin kinase is required for meiosis I in mouse oocytes. Journal of Cell Science. 127(23): 5066-78.
Balboula, AZ, and Schindler, K. 2014. Selective Disruption of Aurora C Kinase Reveals Distinct Functions From Aurora B Kinase During Meiosis in Mouse Oocytes. Plos Genetics.10(2):e1004194.
Balboula, AZ, Stein, P, Schultz, RM and Schindler, K. 2014. Knockdown of RBBP7 unveils a requirement of histone deacetylation for CPC function in mouse oocytes. Cell Cycle. 13(4):600-11.
Oh JS, Susor A, Schindler K, Schultz RM, Conti M. 2013. Cdc25A activity is required for the metaphase II arrest in mouse oocytes. Journal of Cell Science. 126(Pt 5): 1081-5.
Schindler K*, Davydenko O*, Fram B, Lampson MA, Schultz RM. 2012. Maternally-recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. PNAS 109(33): E2215-22.