I am a former Research Councils United Kingdom fellow and currently Associate Professor in Reproductive Medicine at Warwick Medical School. I began my Glaxo-Wellcome Prize PhD studentship at the University of Cambridge before completing my studies on oxytocin in pregnancy at the University of Warwick.
In subsequent years and in parallel to my interests in mammalian parturition, I became interested in the function of cellular heterogeneity in complex tissues and the correlation of physiological data with molecular biology with particular consideration given to levels of biological organisation. This led to a period of study in the lab of Prof. David Spanswick, developing mRNA amplification methods after electrophysiological experimentation in single cells. Since then, I have been part of a national collaboration to assemble a computational model of the pregnant human uterus based on accurate biophysical, molecular and anatomical parameters.
In addition, I have published on the role of the T-type calcium channel in human myometrium, developed a new slice preparation of human myometrium for physiological analysis and documented the genomic complement of K+ channels expressed in human and mouse myometrial and vascular smooth muscle. From these studies we aim to identify novel treatments to target manipulation of uterine contractility in both preterm and dysfunctional labour.
My lab currently employs 3 PhD students working on computational models of myometrial smooth muscle and ion channel pharmacology and two post-doctoral scientists working on laser capture microdissection and ion-channel profiling/electrophysiology. I am a member of the Physiological Society and have given invited lectures nationally to the Institute of Reproductive and Developmental Biology (Imperial College), The Physiological Society (Edinburgh) and The Society for Gynecologic Investigation (San Diego).
- Biophysical modelling of uterine smooth muscle cells with Prof. David Rand (Systems Biology), Dr. Hugo Van den Berg (Systems Biology) and Dr. Anatoly Shmygol (Clinical Sciences Research Institute, CSRI), MRC. Project Start Date: 01/10/2010 Project End Date: 01/10/2014
- The role and regulation of the oxytocin/oxytocin receptor (OT/OTR) system in human amnion and labour with Dr. Vassoliki Terzidou (Institute of Reproductive and Developmental Biology, Imperial College London) and Prof. Steven Thornton, Action Medical Research. Project Start Date: 01/05/2010 Project End Date: 01/05/2013
- The role of the inwardly rectifying potassium channel Kir 7.1 in maintenance of uterine quiescence during pregnancy, MRC: New Investigator Research Grant. Project Start Date: 01/05/2010 Project End Date: 01/05/2013
- MRC New Investigator Grant, with -, MRC. Project Start Date: 01/05/2010 Project End Date: 30/04/2013
- MRC Capacity Building Studentships with Prof. David Rand (Systems Biology), Dr. Andrew Blanks (CSRI) and Dr. Anatoly Shmygol (CSRI), MRC. Project Start Date: 01/10/2008 Project End Date: 30/09/2012
- Specific targeting of nifedipine action to the uterus by manipulation of myometrial specific ion channels with Prof. Steven Thornton (CSRI) and Dr. Anatoly Shmygol (CSRI) Action Medical Research. Project Start Date: 01/01/2010 Project End Date: 01/01/2012
COLLABORATIONS: MODELLING THE UTERUS
We are part of a multi-centre group of UK-based researchers who are developing a computational model of the human and rodent uterus.
This is a collaboration between us and:
- Warwick Systems Biology: Prof. David Rand, Dr. Hugo van den Berg and Dr. Magnus Richardson
- University of Manchester: Dr. Henggui Zhang
- University of Newcastle: Dr. Michael Taggart
- University of Leeds: Prof. Arun Holden
The model works on several levels; from classical Hodgkin-Huxley type modelling of time-dependent active conductances in a single cell through to coupled models of heterogeneous networks.
The collaboration has assembled initial basic models of spatio-temporal patterns of excitability mapped to the full 3D geometry of the pregnant human uterus.
- To have a computer based simulation of the pregnant human uterus
- To test quantitatively scientific ideas of cellular function
- To model the effects of mutations in key genes
- To simulate complex phenomena in order to improve clinical treatments and diagnosis e.g. improved understanding of clinical EHG data
Clark A, Terzidou V, Blanks AM and Thornton S (1999) 5β dihydroprogesterone inhibits spontaneous human myometrial contractions in vitro. BJOG 106 1100
Thornton S, Terzidou V, Clark A and Blanks AM (1999) Progesterone metabolite and spontaneous myometrial contractions in vitro. Lancet 353 (9161) 1329-1331 [PubMed]
Blanks AM and Thornton S (2003) The role of oxytocin in parturition. BJOG 110 Suppl 20 46-51 [PubMed]
Blanks AM, Vatish M, Allen MJ, Ladds G, Dewit NCJ, Slater DM and Thornton S (2003) Paracrine oxytocin and estradiol demonstrate a spatial increase in human intrauterine tissues with labor. J Clin Endocrinol Metab Jul 88 (7) 3392-3400 [PubMed]
Van den Top M, Lee K, Whyment A, Blanks AM and Spanswick D (2004) Orexigen–sensitive NPY-AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nat Neurosci 7 (5) 493-494 [PubMed]
Whyment AD, Blanks AM, Lee K, Renaud L and Spanswick D (2005) Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors. J Neurophys 95 (4) 2492-2500 [PubMed]
Shmygol A, Gullam JE, Blanks AM and Thornton S (2006) Multiple mechanisms involved in oxytocin-induced modulation of myometrial contractility. Acta Pharmacol Sin 27 (7) 827-832 [PubMed]
Holden AV, Pan L, Blanks AM, Evans CJ, Kharche S, Simpson NAB, Smye S, Snowden S, Taggart MJ, Walker JJ and Zhang H (2006) Towards an electrophysiological functional atlas of the uterus in premature and full term labour. Proceedings of the MICCAI Workshop - From Statistical Atlases to Personalized Models: Understanding Complex Diseases in Populations and Individuals.
Blanks AM, Shmygol A and Thornton S (2007) Regulation of oxytocin receptors and oxytocin receptor signalling. Semin Repro Med 25 (1) 52-59 [PubMed]
Shmygol A, Blanks AM, Bru-Mercier G, Gullam JE and Thornton S (2007). Control of uterine Ca2+ by membrane voltage: toward understanding the excitation-contraction coupling in human myometrium. Ann N Y Acad Sci 1101 97-109 [PubMed] REVIEW
Blanks AM, Zhao Z, Shmygol A, Bru-Mercier G, Astle S and Thornton S (2007) Characterization of the molecular and electrophysiological properties of the T-type calcium channel in human myometrium. J Physiol 581 (Pt 3) 915-926 [PubMed]
Taggart MJ, Blanks AM, Kharche S, Holden A, Wang B and Zhang H (2007) Towards understanding the myometrial physiome: approaches for the construction of a virtual physiological uterus. BMC Pregnancy Childbirth 7 Suppl 1:S3. REVIEW [PubMed]
Gullam JE, Blanks AM, Thornton S and Shmygol A (2009) Phase-plot analysis of the oxytocin effect on human myometrial contractility. Eur J Obstet Gynecol Reprod Biol 144 Suppl 1 S20-24 [PubMed]
Higgins CA, Martin W, Anderson L, Blanks AM, Norman JE, McConnachie A and Nelson SM (2010) Maternal obesity and its relationship with spontaneous and oxytocin-induced contractility of human myometrium in vitro. Reprod Sci 17 (2) 177-185 [PubMed]
Vatish M, Steer PJ, Blanks AM, Hon M and Thornton S (2010) Diurnal variation is lost in preterm deliveries before 28 weeks of gestation. BJOG 117 (6) 765-767 [PubMed]
Terzidou V, Blanks AM, Kim SH, Thornton S and Bennett PR (2010) Labor and inflammation increase the expression of oxytocin receptor in human amnion. Biol Reprod [PubMed]
Aslanidi O, Atia J, Benson AP, van den Berg HA, Blanks AM, Choi C, Gilbert SH, Goryanin I, Hayes-Gill BR, Holden AV, Li P, Norman JE, Shmygol A, Simpson NA, Taggart MJ, Tong WC, Zhang H (2011) Towards a computational reconstruction of the electrodynamics of premature and full term human labour.
Prog Biophys Mol Biol. Oct;107(1):183-92. doi: 10.1016/j.pbiomolbio.2011.07.004. Epub 2011 Jul 13. Review.
Blanks AM, Brosens JJ (2012) Progesterone action in the myometrium and decidua in preterm birth
Facts Views Vis Obgyn. 4(3):33-43. Review. PMID: 24753902
Bru-Mercier G, Gullam JE, Thornton S, Blanks AM, Shmygol A (2012) Characterization of the tissue-level Ca2+ signals in spontaneously contracting human myometrium J Cell Mol Med. Dec;16(12):2990-3000. doi: 10.1111/j.1582-4934.2012.01626.x. PMID: 22947266
Kuroda K, Venkatakrishnan R, Salker MS, Lucas ES, Shaheen F, Kuroda M, Blanks A, Christian M, Quenby S, Brosens JJ (2013) Induction of 11β-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells. Mol Endocrinol. Feb;27(2):192-202. doi: 10.1210/me.2012-1247. Epub 2012 Dec 28. PMID: 23275455
Blanks AM, Brosens JJ (2013) Meaningful menstruation: cyclic renewal of the endometrium is key to reproductive success. Bioessays. May;35(5):412. doi: 10.1002/bies.201300022. PMID: 23580337
Sheldon RE, Baghdadi M, McCloskey C, Blanks AM, Shmygol A, van den Berg HA (2013) Spatial heterogeneity enhances and modulates excitability in a mathematical model of the myometrium J R Soc Interface. Jul 10;10(86):20130458. doi: 10.1098/rsif.2013.0458. Print 2013 Sep 6. PMID: 23843249
Brosens JJ, Blanks AM, Lucas ES (2013) LRH-1: orphaned, adopted and needed for pregnancy. Nat Med. Aug;19(8):968-9. doi: 10.1038/nm.3271. PMID: 23921740
Chan YW, van den Berg HA, Moore JD, Quenby S, Blanks AM (2014) Assessment of myometrial transcriptome changes associated with spontaneous human labour by high-throughput RNA-seq. Exp Physiol. 2014 Mar;99(3):510-24. doi: 10.1113/expphysiol.2013.072868. Epub 2013 Nov 22. PMID: 24273302
McCloskey C, Rada C, Bailey E, McCavera S, van den Berg HA, Atia J, Rand DA, Shmygol A, Chan YW, Quenby S, Brosens JJ, Vatish M, Zhang J, Denton JS, Taggart MJ, Kettleborough C, Tickle D, Jerman J, Wright P, Dale T, Kanumilli S, Trezise DJ, Thornton S, Brown P, Catalano R, Lin N, England SK, Blanks AM (2014) The inwardly rectifying K+ channel KIR7.1 controls uterine excitability throughout pregnancy. EMBO Mol Med. Jul 23;6(9):1161-74. doi: 10.15252/emmm.201403944. PMID: 25056913
Sheldon RE, Mashayamombe C, Shi SQ, Garfield RE, Shmygol A, Blanks AM, van den Berg HA (2014) Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium. J R Soc Interface. Dec 6;11(101):20140726. PMID: 25401181
Kim SH, MacIntyre DA, Firmino Da Silva M, Blanks AM, Lee YS, Thornton S, Bennett PR, Terzidou V. (2015) Oxytocin activates NF-κB-mediated inflammatory pathways in human gestational tissues. Mol Cell Endocrinol. Mar 5;403:64-77. doi: 10.1016/j.mce.2014.11.008. Epub 2014 Nov 14. PMID: 25451977
Wright PD, Kanumilli S, Tickle D, Cartland J, Bouloc N, Dale T, Tresize DJ, McCloskey C, McCavera S, Blanks AM, Kettleborough C, Jerman JC (2015) A High-Throughput Electrophysiology Assay Identifies Inhibitors of the Inwardly Rectifying Potassium Channel Kir7.1. J Biomol Screen. Jul;20(6):739-47. doi: 10.1177/1087057115569156. Epub 2015 Feb 5. PMID: 25656238
Sheldon RE, Shmygol A, van den Berg HA, Blanks AM (2015) Functional and morphological development of the womb throughout life. Sci Prog. 98(Pt 2):103-27. Review. PMID: 26288915
Lammers WJ, Stephen B, Al-Sultan MA, Subramanya SB, Blanks AM (2015) The location of pacemakers in the uteri of pregnant guinea pigs and rats. Am J Physiol Regul Integr Comp Physiol. Dec 1;309(11):R1439-46. doi: 10.1152/ajpregu.00187.2015. Epub 2015 Sep 16. PMID: 26377559
Kim SH, MacIntyre DA, Hanyaloglu AC, Blanks AM, Thornton S, Bennett PR, Terzidou V (2016) The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via Gαi signalling.
Mol Cell Endocrinol. Jan 15;420:11-23. doi: 10.1016/j.mce.2015.11.012. Epub 2015 Nov 14. PMID: 26586210
Atia J, McCloskey C, Shmygol A, Rand D.A., van den Berg H, Blanks AM (2016) Reconstruction of cell surface densities of ion pumps, exchangers, and channels from mRNA expression, conductance kinetics, whole-cell calcium, and current-clamp voltage recordings, with an application to human uterine smooth muscle cells. PLoS Computational Biology, Apr 22;12(4):e1004828. PMID: 27105427
Muter J, Brighton PJ, Lucas ES, Lacey L, Shmygol A, Quenby S, Blanks AM, Brosens JJ (2016) Progesterone-Dependent Induction of Phospholipase C-Related Catalytically Inactive Protein 1 (PRIP-1) in Decidualizing Human Endometrial Stromal Cells. Endocrinology. 2016 May 11:en20151914. [Epub ahead of print] PMID: 27167772
Blanks AM and Thornton S (2007) Gene redundancy: Lessons for Tocolysis. in Preterm Birth: Mechanisms, Mediators, Prediction & Interventions. Editors: Petraglia, F, Strauss JF, Gabbe SG, & Weiss G
Blanks AM, Shmygol A and Thornton S (2007) Preterm labour. Myometrial Function & Prematurity. In Best Practice & Research Clinical Obstetrics & Gynaecology : Preterm Birth. Eds: Bennett P and Thornton S 21 (5) 807-819 [PubMed]
Blanks AM, McAulay JA and Sneddon JM (1995) Effect of cisplatin on glucose uptake in immortalised human kidney cells (G401) Br J Pharmacol 116 213p
Clark A, Terzidou V, Blanks AM and Thornton S (1999) Spontaneous and oxytocin-induced human myometrial contractions are inhibited by 5β dihydroprogesterone in vitro. J Soc Gynecol Invest 6 43
Blanks AM, Allen MJ, Slater DM and Thornton S (2001) Oxytocin and not vasopressin is differentially expressed within the human uterus. J Soc Gynecol Invest 8 202A
Blanks AM, Slater DM, Lee K, Richardson PJ and Thornton S (2002) Analysis of heterogeneous gene expression and phenotype in single human myometrial cells by Three Prime End Amplification-RT-PCR (TPEA-RTPCR) J Soc Gynecol Invest
Vatish M, Blanks AM, Ladds GR and Thornton S (2002) Determination Of Oxytocin Peptide/Oestradiol Concentrations in Human Labour and Non-Labour Gestational Tissues. J Soc Gynecol Inv 9 (Suppl) 134A
Blanks AM, Vatish M, Ladds G, Slater DM and Thornton S (2002) Paracrine oxytocin and oestradiol during pregnancy and parturition in human intrauterine tissues. BJOG 109 483-484
Blanks AM, Vatish M, Slater DM and Thornton S (2004) Expression of keto-steroid reductase 2, 4, 5, 7 and 8 mRNA in human choriodecidua throughout gestation. J Soc Gynecol Inv 11 323A
Blanks AM, Zhao ZH and Thornton S (2005) Functional heterogeneity of the t-type calcium channel subunit cav3.1 and cav3.2 in human myometrium. J Soc Gynecol Inv 12 118
Taggart MJ, Zhang H, Kharche S, Holden AV, Thornton S and Blanks AM (2005) Integrative approaches towards understanding the myometrial physiome. J Soc Gynecol Inv 12
Shmygol A, Blanks AM, Bru-Mercier G, Astle S and Thornton S (2006) Tissue-level Ca2+ signalling in human myometrium: a possible role for ICCs Proc Physiol Soc 3 C114
Shmygol A, Blanks AM, Bru-mercier G, Spanswick D and Thornton S (2006) Ultra-thin tissue slices - a new approach to study Ca2+ signalling in human myometrium. J Biomech 39 S341 6476.
Gullam JE, Blanks AM, Shmygol A and Thornton S (2006) Two components in the oxytocin-induced potentiation of myometrial contractility. BJOG
Bru-Mercier G, Shmygol A, Thornton S and Blanks AM (2007) A new model to study myometrial complexity and heterogeneity. Reproductive Sciences Vol. 14 No 1 (Supplement) p233A
Bru-Mercier G, Shmygol A, Thornton S and Blanks AM (2007) Effects of mechanical stretch on inter- and intracellular Ca2+ signals in ultra-thin slices of myometrium. Proc Physiol Soc
Fyfe GK, Bru-Mercier G, Blanks AM, Shymgol A, Thornton S, Khan RN and Taggart MJ (2007) A shared pathway for hydrogen peroxide and 4-aminopyridine inhibition of whole-cell K+ currents in isolated human uterine smooth muscle cells. J Physiol
Gullam JE, Blanks AM, Thornton S and Shmygol A (2008) Oxytocin-induced myometrial contractions in the presence of nifedipine, What is the mechanism? Reproductive Sciences 15 (1) A192
Bru-Mercier G, Shmygol A, Thornton S and Blanks AM (2008) Spontaneous activity and the complex action potential require the myometrial network. Reproductive Sciences 15 (1) A188.
Higgins CA, Martin W, Blanks AM, Thornton S, Norman JE and Nelson SM (2008) Maternal obesity does not impair spontaneous or oxytocin induced contractility of human myometrium. Reproductive Sciences 15 (1) A184.
Bru-Mercier G, Gullam JE, Blanks AM, Thornton S and Shmygol A (2008) Oxytocin-induced oscillations of isometric force and cytoplasmic Ca2+ in slices of human myometrium subjected to inhibition of Ca2+ channels. J Physiol
Jimenez-Roldan EJ, Bru-Mercier G, Blanks AM, Thornton S and Shmygol A (2009) Extracellular cyclic ADP-ribose modulates Ca2+ signalling in human myometrium. J Soc Gynecol Inv 451
Bailey E, Bradley A, Blanks AM, Shmygol A, Gordon D and Thornton S (2009) Effects of a ß3-adrenoceptor agonist, solabegron, on spontaneous myometrial contractility in isolated human myometrial strips. J Soc Gynecol Inv 762
Bailey E, Bradley A, Shmygol A, Thornton S, Blanks AM (2009) Combination therapy using potassium channels openers and nifedipine in human myometrium in vitro. J Soc Gynecol Inv 763
Higgins CA, Martin W, Blanks AM, Thornton S, Nelson SM (2009) Investigation of myometrial gene expression in response to sustained spontaneous and oxytocin-induced contraction in vitro. J Soc Gynecol Inv 773
Higgins CA, Martin W, Blanks AM, Catalano R, Thornton S, Nelson SM (2010) Myometrial cytokines and chemokines during human labour: a co-ordinated time and contraction dependent event. J Soc Gynecol Inv 401
Zhang J, Taggart MJ, Thornton S, Shmygol A, Blanks AM (2010) The pregnancy dependent expression profile of the genomic complement of K+ channels in human myometrial smooth muscle and vasculature. J Soc Gynecol Inv 42
Blanks AM, Tong WC, Benson AP, Holden AV (2010) Digital reconstruction of the fibre architecture of the pregnant human uterus in vivo and in vitro by diffusion MRI. J Soc Gynecol Inv 930
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