My work will elucidate how chromosome and centrosome dynamics are coordinately regulated by Polo-Like Kinase 4 (PLK4) during meiotic prophase I to ensure fertility and healthy embryonic development. To study these processes, I am implementing a combination of cellular, genetic, and biochemical approaches to further our understanding of how polo-like kinases influence cell cycle progression and quality-control in the mammalian germline.
Polo-like kinases represent a family of evolutionarily conserved serine-threonine protein kinases that are involved in various cell-cycle related processes. Polo-Like Kinase 4 (PLK4) is a structurally divergent member of the PLK family that acts as the master-regulator of centrosome duplication’ during S-phase in somatic cells, and following completion of DNA repair and synapsis in during meiosis in spermatocytes. Mutations in PLK4 have been implemented in various disorders that affect human health, including microcephaly, dwarfism, retinopathy, poor cancer prognosis, and infertility.
The role of PLK4 during the meiotic centrosome cycle is not well-characterized, however, we recently discovered that in addition to the centrosome, PLK4 specifically localizes to discrete nuclear subdomains during meiotic progression in both males and females, suggesting that PLK4 is directly involved in nuclear DNA repair processes, as well as in mediating crosstalk between the centrosome and the nucleus during meiotic DNA damage checkpoint responses.
My current work entails using a mutant mouse model that expresses a dominant-negative allele of Plk4 to study how PLK4-mediated post-translational modifications contribute toward meiotic progression at both the centrosomes and within the nucleus in developing spermatocytes and oocytes. In addition to our mouse model, I am using additional phosphoproteomic and molecular approaches to further test our hypothesis that PLK4 mediates cross-talk between nuclear and centrosomal processes throughout prophase I.
Past research experience:
July 2012-June 2013: Tang Lab, JHSPH, Division of Molecular Toxicology
I determined and assessed epigenetic biomarkers of Bisphenol A and allergen exposure, specifically methylation changes within CpG islands of genes involved in Th1/Th2 immune responses during childhood asthma pathogenesis.