The Niakan Lab is based in the Loke Centre for Trophoblast Research (Loke CTR) within the Department of Physiology, Development and Neuroscience (PDN) at the University of Cambridge. We are affiliated members of the Cambridge Stem Cell Institute (CSCI) and the Epigenetics Programme at the Babraham Institute. In addition, we are members of the Cambridge Reproduction Interdisciplinary Research Centre.
Research interests
The goal of our research is to understand how cells specialise and organise into functional tissues, organs and ultimately the entire human organism by integrating genetic, cellular and tissue-scale dynamics. Our focus is on pre- and early post-implantation development, where our knowledge of these processes in humans remains rudimentary, despite its importance for understanding pregnancy complications, developmental disorders, and stem and progenitor cells. While model organisms have provided foundational insights into principles of development, human embryogenesis is unique in many critical respects, particularly around the time of implantation. These differences include unique strategies for embryo implantation and placentation, developmental timing, and morphogenesis.
To achieve an integrated, comprehensive understanding of human embryogenesis, we study human embryos directly to elucidate the molecular, cellular, temporal, lineage, and morphogenetic mechanisms of pre to post-implantation development. We seek to uncover when and how human embryonic epiblast, yolk sac and placental progenitor cells are established and maintained, and to understand the molecular mechanisms that distinguish cells lineages.
Dysregulated human embryonic development and implantation results in miscarriage, pregnancy complications, developmental disorders and infertility, with long-term impacts on both maternal and fetal health. Understanding the mechanisms underlying these earliest stages of development is essential to clinical intervention. Determining the molecular mechanisms regulating development of human embryonic cells is also essential to optimise the generation of stem cell lines used in regenerative medicine, and to expand our repertoire of organoid and stem cell-based embryo model systems. 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 expertise
Our laboratory has pioneered approaches to investigate gene function in human embryonic development. We obtained the first nationally regulated research licence to perform CRISPR-Cas9 genome editing in human embryos. We have optimised protein depletion and signalling perturbation methods to uncover the timing and mechanisms underlying the first and second cell fate decisions in humans. We have used novel single-cell multi-omics, comprehensive protein expression and genome editing approaches to discover gene regulatory networks specific to human embryos. We have used single-cell and functional studies to define mechanisms that are evolutionarily conserved across mammals. We have applied novel technologies including light-sheet microscopy and machine learning-based image analysis of labelled human embryos to demonstrate de novo mutations at late stages of development, which has implications for clinical screening. These discoveries validate that, despite the immense challenges, there is a need to study human embryos directly. We have improved human stem cell culture media by leveraging insights from functional analysis of human embryos to more closely recapitulate physiologically relevant conditions. 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 to yolk sac or placental progenitor cells.
Other links
Lab’s PDN departmental profile
Niakan lab 