Medicine

Franchesca Houghton

BSc(Hons), DPhil

Primary position:
Senior Lecturer in Stem cells & Developmental Biology
Other positions:
Deputy Director of Postgraduate Studies

Background

The University of Southampton

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.

Dr Houghton leads a research group with 2 main foci:

1) Understanding the molecular mechanisms which regulate different types of stem cell.
2) Investigating the Biochemistry of mammalian preimplantation embryo development.

Dr Houghton’s research laboratory is based within the Faculty of Medicine campus and comprises both clinical and non-clinical scientists and postgraduate students. Those interested in joining her group either as potential students, Post Doctoral, or Clinical scientists are encouraged to contact Dr Houghton.

Qualifications

BSc(Hons) Biomedical Sciences, University of Wolverhampton 1993
DPhil Biology, University of York, 1997

Appointments held

Post Doctoral Research Fellow, Department of Physiology, University of Western Ontario, London, Ontario, Canada. 1997-1999

Post Doctoral Research Fellow, Department of Biology, University of York. 1999-2002

Wellcome Trust Research Career Development Fellow, Department of Biology, University of York. 2002-2005

Wellcome Trust Research Career Development Fellow, School of Medicine, University of Southampton. 2005-2006

Lecturer, School of Medicine, University of Southampton. 2006-2008

Senior Lecturer, Faculty of Medicine, University of Southampton. 2008-present

Dr Franchesca Houghton's photo

Publications

The University of Southampton's electronic library (e-prints)

Article

Christensen, David R., Calder, Philip C. and Houghton, Franchesca D. (2014) Effect of oxygen tension on the amino acid utilisation of human embryonic stem cells. Cellular Physiology and Biochemistry, 33, (1), 237-246. (doi:10.1159/000356665).
Pfeiffer, Martin J., Esteves, Telma C., Balbach, Sebastian T., Araúzo-Bravo, Marcos J., Stehling, Martin, Jauch, Anna, Houghton, Franchesca D., Schwarzer, Caroline and Boiani, Michele (2013) Reprogramming of two somatic nuclei in the same ooplasm leads to pluripotent embryonic stem cells. Stem Cells, 31, (11), 2343-2353. (doi:10.1002/stem.1497). (PMID:23922292).
Forristal, Catherine E., Christensen , DavidR., Chinnery, Fay E., Petruzzelli, Raffaella, Parry, Kate L., Sanchez-Elsner, Tilman and Houghton, Franchesca D. (2013) Environmental oxygen tension regulates the energy metabolism and self-renewal of human embryonic stem cells. PLoS ONE, 8, (5), e62507. (doi:10.1371/journal.pone.0062507). (PMID:23671606).
Pfeiffer, M.J., Esteves, T.C., Balbach, S.T., Arauzo-Bravo, M.J., Stehling, M., Jauch, A., Houghton, F.D. and Boiani, M. (2012) 26 reprogramming of two somatic nuclei in the same mouse ooplasm leads to pluripotent not totipotent embryos. Reproduction Fertility and Development, 25, (1), 160. (doi:10.1071/RDv25n1Ab26). (PMID:23244860).
Balbach, Sebastian Thomas, Esteves, Telma Cristina, Houghton, Franchesca Dawn, Siatkowski, Marcin, Pfeiffer, Martin Johannes, Tsurumi, Chizuko, Kanzler, Benoit, Fuellen, Georg and Boiani, Michele (2012) Nuclear reprogramming: kinetics of cell cycle and metabolic progression as determinants of success. PLoS ONE, 7, (4), e35322. (doi:10.1371/journal.pone.0035322).
Lazzari, G., Colleoni, S., Duchi, R., Galli, A., Houghton, F.D. and Galli, C. (2011) Embryonic genotype and inbreeding affect preimplantation development in cattle. Reproduction, 141, (5), 625-632. (doi:10.1530/REP-10-0282). (PMID:21310813).
Picton, Helen M., Elder, Kay, Houghton, Franchesca D., Hawkhead, Judith A., Rutherford, Anthony J., Hogg, Jan E., Leese, Henry J. and Harris, Sarah E. (2010) Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro. Molecular Human Reproduction, 16, (8), 557-569. (doi:10.1093/molehr/gaq040).
Forristal, Catherine E., Wright, Kate L., Hanley, Neil A., Oreffo, Richard O.C. and Houghton, Franchesca D. (2010) Hypoxia inducible factors regulate pluripotency and proliferation in human proliferation in human embryonic stem cells cultured at reduced oxygen tensions. Reproduction, 139, (1), 85-97. (doi:10.1530/REP-09-0300).
Mirmalek-Sani, S.H., Stokes, P.J., Tare, R.S., Ralph, E.J., Inglis, S., Hanley, N.A., Houghton, F.D. and Oreffo, R.O. (2009) Derivation of a novel undifferentiated human fetal phenotype in serum-free cultures with BMP-2. Journal of Cellular and Molecular Medicine, 13, (9B), 3541-3555. (doi:10.1111/j.1582-4934.2009.00742.x). (PMID:19438813).
Kimber, S.J., Sneddon, S.F., Bloor, D.J., El-Bareg, A.M., Hawkhead, J.A., Metcalfe, A.D., Houghton, F.D., Leese, H.J., Rutherford, A., Lieberman, B.A. and Brison, D.R. (2008) Expression of genes involved in early cell fate decisions in human embryos and their regulation by growth factors. Reproduction, 135, (5), 635-647. (doi:10.1530/REP-07-0359).
Mirmalek-Sani, S. H., Tare, R. S., Hayes, A. J., Caterson, B., Hanley, N. A., Houghton, F. D. and Oreffo, R. O. C. (2007) Characterisation of human fetal progenitor populations and response to osteogenic growth factors: a model system for mesenchymal lineage differentiation. Tissue Engineering, 13, (7), p.1654. (doi:10.1089/ten.2007.1501).
Eckert, Judith J., Houghton, Franchesca D., Hawkhead, Judith A., Balen, Adam H., Leese, Henry J., Picton, Helen M., Cameron, Iain T. and Fleming, Tom P. (2007) Human embryos developing in vitro are susceptible to impaired epithelial junction biogenesis correlating with abnormal metabolic activity. Human reproduction, 22, (8), 2214-24. (doi:10.1093/humrep/dem147).
Stokes, Paula J., Hawkhead, Judith A., Fawthrop, Richard K., Picton, Helen M., Sharma, Vinay, Leese, Henry J. and Houghton, Franchesca D. (2007) Metabolism of human embryos following cryopreservation: implications for the safety and selection of embryos for transfer in clinical IVF. Human Reproduction, 22, (3), 829-835. (doi:10.1093/humrep/del447).
Webster, A., Houghton, F.D., Leese, H.J. and Aylott, J.W. (2007) The delivery of PEBBLE nanosensors to measure the intracellular environment. Biochemical Society Transactions, 35, (3), 538-543.
Manser, Rosemary C. and Houghton, Franchesca D. (2006) Ca2+ -linked upregulation and mitochondrial production of nitric oxide in the mouse preimplantation embryo. Journal of Cell Science, 119, (10), 2048-2055. (doi:10.1242/jcs.02927).
Houghton, Franchesca D. and Leese, Henry J. (2004) Metabolism and developmental competence of the preimplantation embryo. European Journal of Obstetrics & Gynecology and Reproductive Biology, 115, (Supplement 1), S92-S96. (doi:10.1016/j.ejogrb.2004.01.019).
Houghton, Franchesca D. (2004) Preimplantation embryo metabolism. Biology of Reproduction, (Supplement), p.81.
Manser, R.C., Leese, H.J. and Houghton, F.D. (2004) Effect of inhibiting nitric oxide production on mouse preimplantation embryo development and metabolism. Biology of Reproduction, 71, (2), 528-533. (doi:10.1095/biolreprod.103.025742).
Ghassemifar, M. Reza, Eckert, Judith J., Houghton, Franchesca D., Picton, Helen M., Leese, Henry J. and Fleming, Tom P. (2003) Gene expression regulating epithelial intercellular junction biogenesis during human blastocyst development in vitro. Molecular Human Reproduction, 9, (5), 245-252. (doi:10.1093/molehr/gag033).
Eckert, J.J., Houghton, F.D., Hawkhead, J.A., Leese, H.J., Picton, H., Cameron, I.T. and Fleming, T.P. (2003) Differentiation and metabolic activity are related in cultured human embryos. Pediatric Research, 53, (6), 48A-49A.
Clyde, Julie M., Houghton, Franchesca D., Rutherford, Anthony J., Hogg, Jan E., Leese, Henry J. and Picton, Helen M. (2002) Abstract. Assessment of aneuploidy and developmental potential of human embryos by fluorescence in situ hybridisation and amino acid profiling. Fertility and Sterility, 78, (Supplement 1), p.S185. (doi:10.1016/S0015-0282(02)03891-8).
Houghton, F.D., Barr, K.J., Walter, G., Gabriel, H.D., Grummer, R., Traub, O., Leese, H J., Winterhager, E. and Kidder, G.M. (2002) Functional significance of gap junctional coupling in preimplantation development. Biology of Reproduction, 66, (5), 1403-1412.
Houghton, Franchesca D., Hawkhead, Judith A., Humpherson, Peter G., Hogg, Jan E., Balen, Adam H., Rutherford, Anthony J. and Leese, Henry J. (2002) Non-invasive amino acid turnover predicts human embryo developmental capacity. Human Reproduction, 17, (4), 999-1005. (doi:10.1093/humrep/17.4.999).

Book Section

Houghton, Franchesca D. (2013) Identification of viable embryos by noninvasive measurement of amino acids in culture media. In, Gardner, David K., Sakkas, Denny, Seli, Emre and Wells, Dagan (eds.) Human Gametes and Preimplantation Embryos Assessment and Diagnosis. , Springer, 267-273. (doi:10.1007/978-1-4614-6651-2_24).
Houghton, Franchesca D. (2012) Media composition: amino acids and cellular homeostasis. In, Embryo Culture Methods and Protocols. , Humana Press, 97-106. (Methods in Molecular Biology, 912). (doi:10.1007/978-1-61779-971-6_7).
 

Research

Research Interests

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, human and murine 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.

Specific areas of interest are:

1) The biochemistry and physiology of the ICM and the trophectoderm.
2) The role of nitric oxide in the regulation of embryo metabolism and development.
3) The effect of maternal lifestyle on the nutrient composition of the reproductive tract.

Funding

Dr Houghton is grateful for funding from the MRC, Wellcome Trust, Gerald Kerkut Charitable Trust, Society for Reproduction and Fertility, Kids Kidney Research and Faculty Medicine University of Southampton.

Primary research group:  Human Development and Health

Figure 1 hES cells and EBs

A phase contrast image of a hES cell colony cultured on mouse embryonic fibroblasts (A). Pluripotency verified using immunocytochemistry for OCT4 (B) and TRA-1-60 (C). Embryoid bodies (D) generated fr

Figure 1 hES cells and EBs

Figure 2 Preimplantation embryos

Laser scanning confocal mid plane section through a 2-cell embryo incubated with (A) a NO-sensitive probe (DAF-FM DA) displaying NO production and (B) mitotracker deep red to label mitochondria. A bla

Figure 2 Preimplantation embryos

Responsibilities

Postgraduate student supervision

2005 Rosemary Manser PhD
2010 Catherine Forristal PhD
2010 Ayshe Ismail PhD

Current

Raffaella Petruzzelli
David Christensen
Pardis Arvinrad
Sophia Sander

Academic Clinical Fellow

Alexandra Kermack

Postdoctoral Research Fellow

Dr Irina Fesenko

Faculty of Medicine

Person Responsible for the Human Fertilisation and Embryology Authority (HFEA) research licence for the Centre for Human Development, Stem Cells & Regeneration
Postgraduate student staff representative
Member of Postgraduate Research Management Committee
Member of Postgraduate Student Progress Committee
Member of Integrated PhD Programme Curriculum Development and Assessment Sub-Committee
Member of 4 year Integrated PhD Programme Working Group
Deputy Director of Postgraduate Studies
Postgraduate student pastoral advisor

National and International responsibilities

Member of the HFEA Licensed Centres Panel
Member of the Programme Committee for the Society for Reproduction and Fertility
Chair of Programme Committee for the Society for Reproduction and Fertility
Chair of joint programme committee for the World Congress in Reproductive Biology 2014
Member of the Local organising committee for the World Congress in Reproductive Biology 2014

Teaching Responsibilities

Integrated PhD Stem Cell Pathway. Coordinator and continuity marker of the Stem Cell Biology module. Facilitator for Research Skills for Biomedical Science. Research project supervisor.

PhD. Lecture on stem cell research in the Faculty of Medicine’s PhD student training programme. Organise Unit induction programme for postgraduate students.

MMedSc. Offer laboratory project placements which investigate the regulation of human embryonic stem cell maintenance and how to direct differentiation towards specific lineage pathways.

BMedSc. Offer laboratory project placements which investigate the regulation of human embryonic stem cell pluripotency.

BSc Biomedical Sciences. Lectures on preimplantation embryo development, IVF and preimplantation genetic diagnosis of disease
Offer laboratory project placements

 

Contact

Dr Franchesca Houghton
Faculty of Medicine
University of Southampton
Duthie Building (MP 808)
Southampton General Hospital
Tremona Road
Southampton SO16 6YD

Room Number: SGH//MP808

Telephone: (023) 8120 8731
Email: F.D.Houghton@soton.ac.uk