Katia Carneiro de Paula, Ph.D.

Research

My lab studies mechanisms by which epigenetic signatures are established at very early developmental stages and how epigenetic profiles are propagated throughout development, giving rise to gene expression patterns that are crucial for organ morphogenesis. Soon after the egg has been fertilized, the growth and development of the early embryo will be regulated by maternal determinants such as mRNA and proteins, present in the unfertilized egg. Ultimately, maternal components will be key players for defining the major axes of the developing embryo important for late organ morphogenesis. One important aspect of early animal development, taking place before zygotic transcription starts, is the establishment of epigenetic programs. Although the epigenome of somatic cells is generally stable, epigenetic modifications occur on a genome-wide scale during initial stages of animal development. Epigenetic reprogramming plays a major role in imprinting, acquisition of totipotency and pluripotency and epigenetic inheritance across generations. Although it has been shown a clear role for epigenetic signatures linked to transcriptional activity, the maternal mechanisms that poise genes for late expression under transcriptional silence are not well understood. Currently, I am investigating the role of maternal Histone Deacetylases (HDACs) during organ morphogenesis. HDACs are enzymes that play a central in controlling the levels of histone acetylation on the DNA. The knockdown of maternal HDAC activity by either pharmacological or molecular approaches disrupts the establishment of the embryonic left-right axis, leading to congenital mal-formations. Our main goal is to elucidate, at the molecular level, how epigenetic signatures are established by early maternal HDAC activity, their importance for axial patterning and subsequent organogenesis.