Professor Kathy Niakan
Genetic regulation of early human development
Email: kkn21@cam.ac.uk
Departmental Affiliation: Physiology, Development and Neuroscience
Research
The goal of our research is 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 decision in humans. 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.
Fluorescent images showing gene expression in human embryos at early and late stage of pre-implantation development, where blue is each cell of the embryo, green is a cell membrane marker, magenta is a placental gene expression. Immunofluorescence analysis of DAPI (blue), F-ACTIN (green), GATA3 (magenta) staining in a human morula (left) and blastocyst (right) stage embryos.
Additional links
Niakan Lab at the Crick Institute
Centre for Trophoblast Research
Cambridge Reproduction SRI Steering Committee
Selected Publications
- Claudia Gerri, Afshan McCarthy, Gregorio Alanis-Lobato, Andrej Demtschenko, Alexandre Bruneau, Sophie Loubersac, Norah M E Fogarty, Daniel Hampshire, Kay Elder, Phil Snell, Leila Christie, Laurent David, Hilde Van de Velde, Ali A Fouladi-Nashta, Kathy K Niakan (2020) Initiation of a conserved trophectoderm program in human, cow and mouse embryos, Nature, 587: 443-447.
- Sissy E Wamaitha, Katarzyna J Grybel, Gregorio Alanis-Lobato, Claudia Gerri, Sugako Ogushi, Afshan McCarthy, Shantha K Mahadevaiah, Lyn Healy, Rebecca A Lea, Miriam Molina-Arcas, Liani G Devito, Kay Elder, Phil Snell, Leila Christie, Julian Downward, James M A Turner, Kathy K Niakan (2020) IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche, Nature Communications, 11(1):764
- Norah M E Fogarty, Afshan McCarthy, Kirsten E Snijders, Benjamin E Powell, Nada Kubikova, Paul Blakeley, Rebecca Lea, Kay Elder, Sissy E Wamaitha, Daesik Kim, Valdone Maciulyte, Jens Kleinjung, Jin-Soo Kim, Dagan Wells, Ludovic Vallier, Alessandro Bertero, James M A Turner, Kathy K Niakan (2017) Genome editing reveals a role for OCT4 in human embryogenesis, Nature, 550: 67–73
- Louise A Hyslop, Paul Blakeley, Lyndsey Craven, Jessica Richardson, Norah M E Fogarty, Elpida Fragouli, Mahdi Lamb, Sissy E Wamaitha, Nilendran Prathalingam, Qi Zhang, Hannah O'Keefe, Yuko Takeda, Lucia Arizzi, Samer Alfarawati, Helen A Tuppen, Laura Irving, Dimitrios Kalleas, Meenakshi Choudhary, Dagan Wells, Alison P Murdoch, Douglass M Turnbull, Kathy K Niakan, Mary Herbert (2016) Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease, Nature, 534: 383–386
- Paul Blakeley, Norah M E Fogarty, Ignacio del Valle, Sissy E Wamaitha, Tim Xiaoming Hu, Kay Elder, Philip Snell, Leila Christie, Paul Robson, Kathy K Niakan (2015) Defining the three cell lineages of the human blastocyst by single-cell RNA-seq, Development, 142: 3151-3165
- Sissy E Wamaitha, Ignacio del Valle, Lily T Y Cho, Yingying Wei, Norah M E Fogarty, Paul Blakeley, Richard I Sherwood, Hongkai Ji, Kathy K Niakan (2015) Gata6 potently initiates reprograming of pluripotent and differentiated cells to extraembryonic endoderm stem cells, Genes & Development, 29: 1239-1255