Professor Kathy Niakan

The goal of our research to understand the molecular mechanisms that control early human development. The mechanisms that regulate early cell fate decisions in human development remain poorly understood, despite their fundamental biological importance and wide-reaching clinical implications for understanding infertility, miscarriages, developmental disorders and therapeutic applications of stem cells. We seek to uncover when and how human embryonic epiblast cells are established and maintained, and to understand the molecular mechanisms that distinguish these pluripotent cells from extra-embryonic cells during embryogenesis. We will further develop pioneering methods to investigate gene function during human embryogenesis using CRISPR-Cas9-mediated genome editing, TRIM-Away protein depletion, constitutively active and kinase dead variants of proteins and small molecule inhibitors and activators. These approaches will enable us to directly test the function of genes involved in signalling pathways, and key transcription factors downstream of these pathways, which we hypothesize are involved in the first and second cell fate decisions. Altogether, we seek to make significant advances in our understanding of the molecular programs that shape early human embryogenesis, which has the potential to provide fundamental insights and to drive clinical translation.

Our laboratory has pioneered approaches to investigate the function of genes that regulate human preimplantation embryo development. To date, we have uncovered a mechanism underlying the first lineage decision in human embryogenesis; discovered gene regulatory networks specific to human embryos, which are not found in mouse embryos; and identified mechanisms that are evolutionarily conserved across mammals. These discoveries validate the need to study human embryos directly. By integrating signalling insights gained from transcriptomic analysis of human blastocysts, we have defined human embryonic stem cell (hESC) culture conditions that more closely recapitulate the embryonic niche. The foundational knowledge we have generated will be informative to further improve ex vivo models to better understand human biology. By applying the knowledge we gained from dissecting the molecular programs in the developing embryo, we are identifying signalling pathways and transcription factors that mediate a cell fate switch from a pluripotent embryonic stem cell (ESC) to yolk sac or placental progenitor cells.