Houghton, Franchesca - University of Southampton

个人简介

Dr Houghton was appointed to a Senior Lectureship in the Centre for Human Development, Stem Cells & Regeneration in 2008 having been a Lecturer since 2006. Previously she held a Wellcome Trust Research Career Development Fellowship entitled “Nutrition of the Mammalian Preimplantation Embryo” which she transferred from the University of York to the University of Southampton in 2005. Dr Houghton completed her DPhil in 1997 at the University of York working on the energy metabolism of early mouse embryos. She obtained Post Doctoral experience at the University of Western Ontario, Canada where she investigated the assembly and role of gap junctions in development and cellular homeostasis using connexin43 null mutant mice. This was followed by a further Post Doctoral position at the University of York where she studied the nutrition of the mammalian preimplantation embryo.

研究领域

Dr Houghton’s research is focused on understanding fundamental mechanisms which regulate human embryonic stem cell maintenance and preimplantation embryo development. Hypoxic regulation of human embryonic stem cell maintenance Pluripotent human embryonic stem (hES) cells, derived from the inner cell mass (ICM) of the blastocyst, provide an excellent model to investigate developmental mechanisms since (a) they have the potential to differentiate into all cells of the body, and (b) proliferative culture provides unlimited supplies of hES cells for research and transplantation based therapies. Dr Houghton’s research is focused on understanding mechanisms which regulate hES cell maintenance. Recent data has found that culture at 5% oxygen tension (hypoxia) is beneficial for the maintenance of a highly proliferative, pluripotent population of hES cells compared to atmospheric oxygen tensions. Dr Houghton’s group has found that these effects are regulated by hypoxia inducible factor (HIF)-2α. More specifically, HIF-2αwas found to regulate hES cell proliferation as well as the expression of OCT4, SOX2 and NANOG (Forristal et al., 2010). Current research in Dr Houghton’s group is investigating further mechanisms which regulate this hypoxic response. Metabolism of hES cells The metabolic requirements of hES cells have received relatively little attention. Research in Dr Houghton’s laboratory is investigating the energy metabolism of hES cells and how this is affected upon differentiation. Our recent data has found that hES cells cultured in a low oxygen environment are highly pluripotent and consume high levels of glucose and produce large amounts of lactate. In contrast, hES cells cultured at atmospheric oxygen result in an increased reliance on oxidative metabolism (Forristal et al., 2013). Role of nitric oxide in the maintenance and differentiation of hES cells Nitric oxide (NO) is a pleiotropic signalling molecule central for the maintenance of cellular homeostasis. At low concentrations NO may bind soluble guanylate cyclase to produce cGMP and activate various downstream targets including protein kinases, or may compete with oxygen for binding to cytochrome c oxidase to reduce cellular respiration. At high concentrations NO may react with superoxide anions to yield reactive nitrogen species leading to irreversible damage of mitochondria. Thus, NO can function in a regulatory manner, or adopt a deleterious role within a cell. Current research in Dr Houghton’s group is investigating the regulation of NO signalling during pluripotency and differentiation in hES cells. Kidney stem cells The potential of kidney progenitor cells to differentiate into specific renal cell types holds great promise as an alternative strategy to heal damaged kidneys without the need for transplantation. In collaboration with Dr Jane Collins (Clinical and Experimental Sciences), the Houghton laboratory is isolating and characterising renal progenitor cell populations in human kidneys and investigating their ability to form specific renal cell types. Cancer stem cells In collaboration with Dr Jeremy Blaydes (Cancer Sciences), the Houghton laboratory is investigating the molecular mechanisms which regulate cancer stem cells. Energy metabolism and cell signalling in the mammalian preimplantation embryo Dr Houghton’s research on preimplantation embryos is focused on energy metabolism; the origin and fate of ATP, amino acid turnover, and cell signalling via NO. Her lab has expertise in both the genetic and phenotypic analysis of single preimplantation embryos. The wider aim of Dr Houghton’s work is to improve the success of assisted conception techniques by identifying non-invasive markers of embryo health.

近期论文

查看导师新发文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

GLUT3 and PKM2 regulate OCT4 expression and support the hypoxic culture of human embryonic stem cells - Christensen, David R., Calder, Philip C. and Houghton, Franchesca D. Published:2015Publication:Scientific Reports Volume:5Page Range:17500doi:10.1038/srep17500 The ‘Developmental Origins’ hypothesis: relevance to the obstetrician and gynecologist - Kermack, A. J., Van Rijn, B. B., Houghton, F. D., Calder, P. C., Cameron, I. T. and Macklon, N. S. Published:2015Publication:Journal of Developmental Origins of Health and DiseaseVolume:6, (5)Page Range:415-424doi:10.1017/S2040174415001324 AMPK activation via modulation of de novo purine biosynthesis with an inhibitor of ATIC homodimerization - Asby, Daniel J., Cuda, Francesco, Beyaert, Maxime, Houghton, Franchesca D., Cagampang, Felino R. and Tavassoli, Ali Published:2015Publication:Chemistry & BiologyVolume:22, (7)Page Range:838-848doi:10.1016/j.chembiol.2015.06.008PMID:26144885 Amino acid composition of human uterine fluid: association with age, lifestyle and gynaecological pathology - Kermack, Alexandra J., Finn-Sell, Sarah, Cheong, Ying C., Brook, Nicholas, Eckert, Judith J., Macklon, Nick S and Houghton, Franchesca D. Published:2015Publication:Human ReproductionVolume:30, (4)Page Range:917-924doi:10.1093/humrep/dev008PMID:25697730