Staff Profile
Dr Helen Phillips
Senior Lecturer
- Telephone: +44 (0) 191 241 8698
- Personal Website: https://www.ncl.ac.uk/medical-sciences/research/institutes/biosciences/
- Address: Biosciences Institute
Faculty of Medical Sciences
Newcastle University
International Centre for Life
Central Parkway
Newcastle upon Tyne
NE1 3BZ
United Kingdom
I have a long-standing interest in the heart and my areas of expertise are the genetics of heart development and cardiac disease.
2002 PhD ‘Molecular Genetic Investigation of Hypoplastic Left Heart Syndrome’, Newcastle University;
My PhD focused on identifying the genes disrupted at the chromosomal translocation break point in a patient with Hypoplastic Left heart Syndrome, which could be underlying cause of this severe congenital heart defect.
2002-2008 Post-Doctoral Research Fellow, Newcastle University
My post-doctoral position focused on studying the role of the noncanonical Wnt pathway in heart development using transgenic mouse models.
2008-2011 Newcastle University Fellowship, Newcastle University
During my fellowship I studied the role of Rho Kinase, a small GTPase, in different cell populations contributing to heart development using Cre-LoxP technology.
2011-2017 British Heart Foundation Intermediate Basic Science Fellowship, Newcastle University
I established my own research group and we further investigated the role of Rho Kinase, specifically in the ventricular wall, and how early embryonic defects in the heart can link to cardiac disease.
2017-2022 Lecturer, Newcastle University
2022-present Senior Lecturer, Newcastle University
We have a number of different projects on-going focusing on the role of energy metabolism in cardiomyopathy and the link between development of the ventricular wall and cardiomyopathy.
I am a member of the Biosciences Institute and work in both the Reproduction, Development and Child Health (https://www.ncl.ac.uk/medical-sciences/research/research-themes/reproduction/), and the Vascular Biology and Medicine (https://www.ncl.ac.uk/medical-sciences/research/research-themes/vascular/) Themes.
I am the Deputy Director of Postgraduate Research (Biosciences Institute) and Deputy MRes Exam Committee Chair.
Congenital heart anomalies are one of the most common birth defects, affecting 1 in 145 births. Cardiovascular disease is the main cause of death in the UK, accounting for approximately one third of all deaths. In response to stress on the adult heart, developmental pathways can be reactivated, suggesting that factors that play crucial roles in normal development may be involved in disease processes in adult life.
During heart development, initially, the walls of the ventricles are thin and they thicken as the heart matures. During this time cells from the outer layer of the heart, the epicardium, migrate into the myocardium and influence the maturation process of the heart muscle. During this developmental period and following birth, the cardiomyocytes change from approximately spherical cells into highly polarised rod-shaped cells. Extrapolating the cardiomyocyte maturation process will aid the understanding of the role of individual genes in cardiovascular disease and what preventative measures could be developed.
My research group is therefore investigating how certain genes are important for the growth and maturation of the heart muscle wall. Using transgenic mice, this allows us to study the role of genes of interest, specifically within subsets of the different cell populations essential for normal heart development, using the Cre/LoxP system. We use a number of imaging techniques to model the heart defects and to study gene expression.
We are focusing on a number of intracellular processes (including autophagy) and different genes, including members of the small GTPases family, Rho kinase and Rac1, to determine how they play a role in the maturation of the ventricular wall. We have found a link between embryonic heart defects and the progression to heart disease and therefore opening up the possibility of new candidate genes for cardiomyopathies.
Enquiries are welcome from prospective PhD students who have secured funding, or who wish to apply for funding, with an interest in the genetics of heart development, congenital heart defects and cardiomyopathy.
Postgraduate Teaching:
I am the Module and Programme Lead for the MRes in Cardiovascular Science in Health and Disease (MMB8037). I also teach on MRes in Developmental Genetics (MMB8031).
Each year, MRes students undertake a 6 month research project in our laboratory.
Undergraduate Teaching:
I teach on Biochemistry and Genetics of Signalling and the Cell Cycle (BGM2002), Genetics (BGM1004), Genetics of Development and its Disorders (BGM3061) courses.
In addition, each year I supervise BSc Honours students undertaking their 10 week research project.
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Articles
- Singh E, Phillips HM, Arthur HM. Dynamic changes in endoglin expression in the developing mouse heart. Gene Expression Patterns 2021, 39, 119165.
- Khasawneh RR, Kist R, Queen R, Hussain R, Coxhead J, Schneider JE, Mohun TJ, Zaffran S, Peters H, Phillips HM, Bamforth SD. Msx1 haploinsufficiency modifies the Pax9-deficient cardiovascular phenotype. BMC Developmental Biology 2021, 21, 14.
- Stothard CA, Mazzotta S, Vyas A, Schneider JE, Mohun TJ, Henderson DJ, Phillips HM, Bamforth SD. Pax9 and Gbx2 interact in the pharyngeal endoderm to control cardiovascular cevelopment. Journal of Cardiovascular Development and Disease 2020, 7(2), E20.
- Johnson A-L, Schneider JE, Mohun TJ, Williams T, Bhattacharya S, Henderson DJ, Phillips HM, Bamforth SD. Early embryonic expression of AP-2a is critical for cardiovascular development. Journal of Cardiovascular Development and Disease 2020, 7(3), 27.
- Singh E, Redgrave RE, Phillips HM, Arthur HA. Arterial endoglin does not protect against arteriovenous malformations. Angiogenesis 2020, 23, 559-566.
- Bailey KE, MacGowan GA, Tual-Chalot S, Phillips L, Mohun TJ, Henderson DJ, Arthur HM, Bamforth SD, Phillips HM. Disruption of embryonic ROCK signalling reproduces the sarcomeric phenotype of Hypertrophic Cardiomyopathy. JCI Insight 2019, 4(8), e125172.
- Phillips HM, Stothard CA, Shaikh Qureshi WM, Kousa AI, BrionesLeon JA, Khasawneh RR, Sanders R, O'Loughlin C, Mazzotta S, Dodds R, Seidel K, Bates T, Nakatomi M, Cockell SJ, Schneider JE, Mohun TJ, Maehr R, Kist R, Peters H, Bamforth SD. Pax9 is required for cardiovascular development and interacts with Tbx1 in the pharyngeal endoderm to control 4th pharyngeal arch artery morphogenesis. Development 2019, 146, dev177618.
- Ramsbottom SA, Sharma V, Rhee HJ, Eley L, Phillips HM, Rigby HF, Dean C, Chaudhry B, Henderson DJ. Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development. PLoS Genetics 2014, 10(12), e1004871.
- Phillips HM, Mahendran P, Singh E, Anderson RH, Chaudhry B, Henderson DJ. Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets. Cardiovascular Research 2013, 99(3), 452-460.
- Anderson RH, Chaudhry B, Mohun TJ, Bamforth SD, Hoyland D, Phillips HM, Webb S, Moorman AF, Brown NA, Henderson DJ. Normal and abnormal development of the intrapericardial arterial trunks in humans and mice. Cardiovascular Research 2012, 95(1), 108-115.
- Phillips HM, Papoutsi T, Soenen H, Ybot-Gonzalez P, Henderson DJ, Chaudhry B. Neural Crest Cell Survival is Dependent on Rho Kinase and is Required for Development of the Mid Face in Mouse Embryos. PLoS One 2012, 7(5), e37685.
- Bell E, Richardson G, Jahoda CA, Gledhill K, Phillips HM, Henderson D, Owens WA, Hole N. Dermal stem cells can differentiate down an endothelial lineage. Stem Cells and Development 2012, 21(16), 3019-3030.
- Hunt DP, Sajic M, Phillips H, Henderson D, Compston A, Smith K, Chandran S. Origins of Gliogenic Stem Cell Populations Within Adult Skin and Bone Marrow. Stem Cells and Development 2010, 19(7), 1055-1065.
- Hildreth V, Webb S, Chaudhry B, Peat JD, Phillips HM, Brown N, Anderson RH, Henderson DJ. Left cardiac isomerism in the Sonic hedgehog null mouse. Journal of Anatomy 2009, 214(6), 894-904.
- Phillips HM, Hildreth V, Peat JD, Murdoch JN, Kobayashi K, Chaudhry B, Henderson DJ. Non-cell-autonomous roles for the planar cell polarity gene vangl2 in development of the coronary circulation. Circulation Research 2008, 102(5), 615-623.
- Henderson D, Phillips H. Planar cell polarity signalling plays crucial roles in outflow tract development. Heart 2007, 93, A36-A36.
- Phillips HM, Rhee HJ, Murdoch JN, Hildreth V, Peat JD, Anderson RH, Copp AJ, Chaudhry B, Henderson DJ. Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization. Circulation Research 2007, 101(2), 137-145.
- Phillips HM, Murdoch JN, Chaudhry B, Copp AJ, Henderson DJ. Vangl2 acts via RhoA signaling to regulate polarized cell movements during development of the proximal outflow tract. Circulation Research 2005, 96(3), 292-299.
- Ross AJ, May-Simera H, Eichers ER, Kai M, Hill J, Jagger DJ, Leitch CC, Chapple JP, Munro PM, Fisher S, Tan PL, Phillips HM, Leroux MR, Henderson DJ, Murdoch JN, Copp AJ, Eliot M-M, Lupski JR, Kemp DT, Dollfus H, Tada M, Katsanis N, Forge A, Beales PL. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. Nature Genetics 2005, 37(10), 1135-1140.
- Phillips HM, Renforth GL, Spalluto C, Hearn T, Curtis ARJ, Craven L, Havarani B, Clement-Jones M, English C, Stumper O, Salmon T, Hutchinson S, Jackson MS, Wilson DI. Narrowing the critical region within 11q24-qter for hypoplastic left heart and identification of a candidate gene, JAM3, expressed during cardiogenesis. Genomics 2002, 79(4), 475-478.
- Balmer P, Phillips HM, Maestre AE, McMonagle FA, Phillips RS. The effect of nitric oxide on the growth of Plasmodium falciparum, P-chabaudi and P-berghei in vitro. Parasite Immunology 2000, 22(2), 97-106.
- Wragg M., Hutton M., Talbot C., and the Alzheimer’s Disease Collaborative Group (Busfield F., Woo Han S., Lendon C., Clark R.F., Morris J., Edwards D., Goate A., Pfeiffer E., Crook R., Prihar G., Phillips H., Baker M., Hardy J., Rossor M., Houlden H., Karran E., Roberst G. and Craddock N. Genetic association between intronic polymorphism in presenilin-1 gene and late-onset Alzheimer’s Disease. Lancet 1996, 347, 509-512.
- Hutton M., Busfield F., Wragg M., Crook R., Perez-Tur J., Clark R.F., Prihar G., Talbot C., Phillips H., Wright K., Baker M., Lendon C., Duff K., Martinez A., Houlden H., Nichols A., Karran E., Roberts G., Venter J.V.C., Adams M.D., Clone R.T., Phillips C.A., Fuldener R.A., Hardy J. and Goate A. Complete analysis of the presenilin 1 gene in early-onset Alzheimer’s Disease. Neuroreport 1996, 7, 801-805.
- Perez-Tur J., Croxton R., Wright K., Phillips H., Zehr C., Crook R., Hutton M., Karran E., Roberts G., Lancaster S. and Haltia T. A further presenilin 1 mutation in the exon 8 cluster in familial Alzheimer’s Disease. Neurodegeneration 1996, 5, 207-212.
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Book Chapter
- Booth k, Redgrave R, Tual-Chalot s, Spyridopoulos I, Phillips HM, Richardson GD. Heart Disease and Ageing: The Roles of Senescence, Mitochondria, and Telomerase in Cardiovascular Disease. In: Harris, J.R., Korolchuk, V.I, ed. Biochemistry and Cell Biology of Ageing: Part IV, Clinical Science. Cham, Switzerland: Springer, 2023, pp.45-78.
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Conference Proceedings (inc. Abstracts)
- Phillips H, Boczonadi V, Chaudhry B, Henderson D. 03-P015: Rho kinase is required for cohesive behaviour of neural crest cells during outflow tract morphogenesis. In: Mechanisms of Development: 16th Annual Conference of the International Society of Development Biologists. 2009, Edinburgh, UK: Elsevier Ireland Ltd.
- Ross A, May-Simera H, Eichers E, Kai M, Hill J, Jagger D, Leitch C, Chapple JP, Munro P, Fisher S, Tan P, Phillips H, Leroux M, Henderson D, Murdoch J, Copp A, Eliot MM, Lupski J, Kemp D, Dollfus H, Tada M, Katsanis N, Forge A, Beales P. Disruption of Bardet-Biedl syndrome ciliary proteins perturbs planar cell polarity in vertebrates. In: Genetics Research: 16th Mammalian Genetics and Development Workshop of the Genetics Society. 2006, London, UK: Cambridge University Press.
- Phillips H, Henderson D. Role of the planar cell polarity pathway in the development of the outflow tract. In: Heart: Annual Conference of G-MEX/MICC. 2005, Manchester, UK: BMJ Group.
- Phillips HM, Renforth G, Jackson M, Clement-Jones M, Craven L, Havarani B, Wilson DI. Characterisation of a novel gene on distal 11q as a potential candidate for Hypoplastic Left Heart Syndrome. In: American Journal of Human Genetics. 2001, Cell Press.
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Editorial
- Phillips HM. Protein geranylgeranylation: a possible newplayer in congenital heart defects. Cardiovascular Research 2018, 114(7), 922-924.
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Reviews
- Steele RE, Sanders R, Phillips HM, Bamforth SD. PAX Genes in Cardiovascular Development. International Journal of Molecular Sciences 2022, 23(14), 7713.
- Henderson DJ, Phillips HM, Chaudhry B. Vang-like 2 and noncanonical Wnt signaling in outflow tract development. Trends in Cardiovascular Medicine 2006, 16(2), 38-45.
- Murdoch JN, Henderson DJ, Doudney K, Gaston-Massuet C, Phillips HM, Paternotte C, Arkell R, Stanier P, Copp AJ. Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Human Molecular Genetics 2003, 12(2), 87-98.