Kathy Niakan is Mary Marshall and Arthur Walton Professor of the Physiology of Reproduction and Director of the Loke Centre for Trophoblast Research at the University of Cambridge. She is also Co-Chair of the Cambridge Reproduction Interdisciplinary Research Centre. Kathy is an Honorary Group Leader at the Babraham Institute and Affiliate Member of the Cambridge Stem Cell Institute. Kathy obtained a B.Sc. in Cell and Molecular Biology and a B.A. in English Literature from University of Washington. She obtained her PhD at University of California, Los Angeles, supported by a National Institutes of Health Pre-doctoral Training Grant, Paul D. Boyer Fellowship and a Chancellor’s Dissertation Year Fellowship. She undertook postdoctoral training at Harvard University where she developed an interest in early human development. She was a Loke Centre for Trophoblast Research Next Generation Research Fellow at University of Cambridge. In 2013 she started her laboratory with a focus on mechanisms regulating early human development at the MRC National Institute for Medical Research and subsequently the Francis Crick Institute. Kathy was elected to EMBO membership (2024), awarded the Genetics Society Mary Lyon Medal (2024) and a Blavatnik Award UK Finalist in Life Sciences (2019). Kathy’s laboratory pioneered approaches to investigate the function of genes that regulate early human development and the molecular mechanisms that direct cell fate in human embryos. Her laboratory obtained the first nationally regulated approval to genetically modify human embryos in research which attracted widespread policy interest. This research licence was acquired as part of the permanent collection at the Science Museum in London, where scientific objects from the laboratory have also been exhibited.

Members

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Josephine Blagrove

Cambridge Biosciences DTP PhD Student

The evolution of gene expression in the primitive endoderm, a transient early extra-embryonic tissue, and the structure it ultimately contributes to, the yolk sac, is largely uncharacterised. The yolk sac provides nutrition to the developing embryo before the placenta takes over. Furthermore, it is vital for organ patterning, haemopoiesis, and gut development in many vertebrates.

My research aims to characterise the development of primitive endoderm into the yolk sac across a broad range of vertebrate species using transcriptomics and functional genetics studies.

Contact: jrb252@cam.ac.uk

Publications

Lewin, T., Blagrove, J. and Holland, P. (2023). Rapid evolution of the embryonically expressed homeobox gene LEUTX within primates. Genome Biology and Evolution, 15(6), https://doi.org/10.1093/gbe/evad097. Wynn, J., Arcos, J., Austin, R., Blagrove, J., Bond, S., Carrasco, G., Delord, K., Fisher-Reeves, L., García, D., Gillies, N., Guilford, T., Hawkins, I., Jaggers, P., Kirk, C., Louzao, M., Maurice, L., McMinn, M., Micol, T., Morford, J., Morgan, G., Moss, J., Riera, E., Rodriguez, A., Siddiqi-Davies, K., Weimerskirch, H., Wynn, R., Padget, O. (2024). Climate change drives migratory range shift via individual plasticity in shearwaters. Proceedings of the National Academy of Sciences of the United States of America, 121(6). https://doi.org/10.1073/pnas.2312438121.

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Esther Rosales Sanchez

Lab manager

I use my skills to ensure smooth lab operations by organizing the lab, managing inventory, liaising with various support teams, making sure we are compliant and up to date with our health and safety policies and coordinating the procurement of consumables and equipment. I am also the primary point of contact for onboarding new team members, ensuring they feel welcomed and supported as they transition into the lab environment. Finally, I like organizing social events that contribute to a positive workplace culture.

My approach combines efficiency, attention to detail, and a commitment to creating a well-organized, inclusive, and dynamic lab environment that supports both scientific discovery and team cohesion.

Contact: er626cam.ac.uk

Alumni

Research

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.

Publications

Key publications:

Gerri C., McCarthy A., Scott G.M., Regis M., Stamatiadis P., Brumm S., Simon C.S., Lee J., Montesinos C., Hassitt C., Hockenhull S., Hampshire D., Elder K., Snell P., Christie L., Fouladi-Nashta A.A., Van de Velde H., Niakan K.K. (2023) A conserved role of the Hippo signalling pathway in initiation of the first lineage specification event across mammals. Development. 150(8):dev201112
Lea R.A., McCarthy A., Boeing S., Fallesen T., Elder K., Snell P., Christie L., Adkins S., Shaikly V., Niakan K.K. (2021) KLF17 promotes human naïve pluripotency but is not required for its establishment. Development, 148(22):dev199378.
Gerri C., McCarthy A., Alanis-Lobato G., Demtschenko A., Bruneau A., Loubersac S., Fogarty N.M.E., Hampshire D., Elder K., Snell P., Christie L., David L., Van de Velde H., Fouladi-Nashta A.A. and Niakan K.K. (2020) A conserved molecular cascade initiates trophectoderm differentiation in human, bovine and mouse embryos prior to blastocyst formation. Nature, 587: 443-447.
Wamaitha S.E., Grybel K.J., Alanis-Lobato G., Gerri C., Ogushi S., Mahadevaiah S.K., Healy L., Lea, R.A., Molina-Arcas M., Elder K., Snell P., Christie L., Downward J., Turner J.M.A and Niakan K.K. (2020) IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche. Nature Communications, 11: 764.
Fogarty, N.M.E., McCarthy, A., Snijders, K.E., Powell, B.E., Kubikova, N., Blakeley, P., Lea, R., Elder, K., Wamaitha, S.E., Kim, D., Maciulyte, V., Kleinjung, J., Kim, J.-S., Wells, D., Vallier, L., Bertero, A., Turner, J.M.A. and Niakan K.K. (2017) Genome editing reveals a role for OCT4 in human embryogenesis. Nature, 550(7674): 67-73.
Hyslop L.A., Blakeley P., Craven L., Richardson J., Fogarty N.M., Fragouli E., Lamb M., Wamaitha S.E., Prathalingam N., Zhang Q., O'Keefe H., Takeda Y., Arizzi L., Alfarawati S., Tuppen H.A., Irving L., Kalleas D., Choudhary M., Wells D., Murdoch A.P., Turnbull D.M., Niakan K.K. and Herbert M. (2016) Towards clinical application of pronuclear transfer to prevent mitochondrial DNA disease. Nature, 534(7607): 383-386.
Blakeley P., Fogarty N.M., Del Valle I., Wamaitha S.E., Hu T.X., Elder K., Snell P., Christie L., Robson P. and Niakan K.K. (2015) Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development, 142(20): 3151-3165.
Wamaitha S.E., del Valle I., Cho L.T., Wei Y., Fogarty N.M.E., Blakeley P., Sherwood R.I., Ji H. and Niakan K.K. (2015) Gata6 potently initiates reprogramming of pluripotent and differentiated cells to extraembryonic endoderm stem cells. Genes and Development, 29(12): 1239-1255.