Professor Nick Europe-Finner
Prof of Myometrial Science

Roles and Responsibilities

Member of the School of Surgical and Reproductive Sciences, University of Newcastle upon Tyne, Postgraduate Committee (1999-present)

Assessor of MD and PhD students in the School of Surgical & Reproductive Sciences

Qualifications

1972-1975 B.Sc (First Class Honours)in Biochemistry, London University, Chelsea College.

1976-1979 Ph.D in Biochemistry, London University, St. George's Hospital Medical School

Previous Positions

1980-1981 MRC Post-Doctoral Research Assistant, Department of Physiology, King's college, London University.

1982-1991 SERC Post-Doctoral Research Scientist, Department of Biochemistry, University of Oxford.

1991-1996 Action Research Grant Holder : Nuffield Deparment of Obstetrics and Gynaecology, University of Oxford.

1996-2001 Non-clinical Lecturer (B): Department of Obstetrics & Gynaecology, School of Surgical & Reproductive Sciences, University of Newcastle upon Tyne

Memberships

Member of the American Endocrine Society
Member of FASEB
Member of the MRC Advisory Board (MAB): 1 July 2004-30 June 2008.

Honours and Awards

Admitted to membership of Congregation at Oxford University with M.A. status (1988-1996).
Awarded a discretionary merit award from the Department of Biochemistry, University of Oxford (1990).
Promoted to RAIIA grade by the University of Oxford (1992).

Research Interests

These studies now concentrate on the transcriptional and post-transcriptional processes regulating uterine smooth muscle gene expression. Projects that are currently in progress include:
i) Control of expression of the Galphas gene in the myometrium by PKA mediated phosphorylation of the Sp1-4 transcription factor family.
ii) Regulation of expression of myometrial Galphas and CREM alternative spliced isoforms by the splicing factors SF2/ASF and hnRNPA1
iii) Characterisation and functional analysis of CREB, CREM and ATF1-4 species in the human myometrium during fetal maturation.
iv) Regulation of human myometrial gene expression by cyclic AMP dependent bZIP transcription factors.
v) Elucidation of the transcriptional co-regulators that interact with bZIP proteins to regulate myometrial gene expression
vi) Characterisation and expression of protein kinase A holoenzymes in the human myometrium during pregnancy and labour.
vii) Elucidation of the molecular mechanisms that regulate the regulatory RIIalpha subunit of PKA in myometrial cells
viii)The role of histone deacetylase (HDAC) and HDAC inhibitors in maintaining myometrial quiescence:Potential use of HDAC inhibitors such as TSA, VPA and SAHA as potent tocolytics in preventing premature delivery

For the last ten years I have been collaborating with Professor Adrian Krainer at the Cold Spring Harbor Laboratory (New York, USA) which has involved studies investigating the alternative splicing mechanisms regulating Galphas isoform expression and which is about to be sent for review. We are at present also investigating the splicing processes controlling expression of CREM species in the myometrium.
This programme of work has/is been funded by the Wellcome Trust, MRC and Action Medical Research

Other Expertise

The use of SAGE in gene profiling of clinical tissues and cell types.

Suppression Subtractive hybridisation (SSH) techniques.

Affymetrix Gene Microarrays

Electrophoretic mobility shift (EMSAs) and promoter reporter gene assays.

In vivo/in vitro alternative splicing assays.

Cell signalling methodologies.

Current Work

The myometrial group has during the last few years:
i) Identified and functionally characterised the predominant cAMP related bZIP transcription factors regulating myometrial gene expression during pregnancy and labour. This is has also resulted in the isolation of a previously unknown isoform of ATF2 having potent gene transactivation properties.
ii) Defined for the first time the pre-mRNA processes regulating Galphas and CREM expression in vivo in different cell types.
iii) Shown that the Galphas gene is regulated at the promoter level by PKA via phosphorylation of Sp1 proteins and that this is a biphasic mechanism.
iv) Determined that the RIIalpha regulatory subunit of PKA is up-regulated in the myometrium during pregnancy and then subsequently down-regulated during labour and that this may be an important area for therapeutic intervention in premature deliveries.
v)Determined by microarrays and SSH the spectrum of myometrial genes that are affected by the cAMP dependent bZIP transcription factors CREB, CREMtau2alpha, CREMalpha, ATF2 and a novel isoform we have isolated termed ATF2-sm
vi)Shown that the histone deacetylase (HDAC) inhibitor TSA can increase the expression of the hCG/LH receptor gene in the human myometrium and thus potentially can be used as a potent tocolytic in maintaining uterine quiescence and preventing preterm labour

Future Research

i)Research plans will include the defining the efficacy of a range of HDAC inhibitors including TSA, VPA and SAHA in regulating the hCG/LH, Galphas and RIIalpha genes in the myometrium so as to maintain myometrial relaxation
ii)Define the co-regulators that interact with the cAMP bZIP proteins
to affect myometrial gene expression

Research Roles

Group Leader for 4 Post-doctoral RAIIA/RAIA research Associates,Clinical Research Associate and a Grade D Research Technician

Postgraduate Supervision

Ph.D Supervisor- Dr. N.V. Small 1986-1989 .Oxford University
Dr. B.M. Gammon 1987-1990. Oxford University

Ph.D supervisor
Dr MWJ MacDougall: 2000-2003. University of Newcastle upon Tyne
Dr M Jefferson: 2005-2008. (with Prof AD Rowan). Institute of Cellular Medicine. University of Newcastle upon Tyne
Dr Tamar Moussed Mahmoud Abu-Amara. 2005-2009. Institute of Cellular Medicine University of Newcastle upon Tyne.
Mr C MacDonald: 2009-2012. Ph.D student (with Prof AD Rowan). Institute of Cellular Medicine. University of Newcastle upon Tyne

Esteem Indicators

Referee for grant applications to the (MRC) Medical Research Council (UK)
Referee for grant applications to the (BBSRC) Biotechnology and Biological Sciences Research Council (UK).
Referee for grant applications to the Wellcome Trust.
Referee for grant applications to Action Research
Referee for grant applications to Wellbeing
Referee for grant applications to Tommy’s the baby charity
Referee for grant applications to SPARKS
Referee for grant applications to the Henry Smith Charity
Referee for grant applications to FSIDS
Referee for grant applications to the National Science Foundation (USA).

Referee for the Journal of Clinical Endocrinology and Metabolism.
Referee for Endocrinology
Referee for the American Journal of Obstetrics and Gynaecology
Referee for Acta Obstetrics and Gynaecology Scandinavia
Referee for Molecular Human Reproduction
Referee for Experimental Physiology
Referee for the Journal of Endocrinological Investigation
Referee for the British Journal of Pharmacology
Referee for Reproduction
Referee for Trends in Endocrinology anad Metabolism
Referee for Reproductive Biology and Endocrinology
Referee for Reproductive Sciences

Invited Lectures
International Dictyostelium Meeting, University of Southampton: 1985.
International Dictyostelium Meeting, University of Amsterdam, Holland: 1986.
International Dictyostelium Meeting, University of Cambridge: 1987.
Department of Zoology, University of Oxford: 1988
Department of Zoology, University of Oxford: 1989.
Department of Biological Sciences, Oxford Brookes University: 1994.
SPARKS-Charity Meeting, The Oxfordshire Golf Club, Oxford: 1995
Department of Biological Sciences, University of Warwick: 1995.
MacDonald Club Meeting, University of Newcastle upon Tyne: 1998.
Uterine Contractility Symposium, University of Oxford: 2000
Tommy’s Campaign Researchers Meeting, University of London: 2000
Serono -Expert meeting-Recombinant hCG in preterm labour. Los Angeles USA: 2002
Society of Gynecologic Investigations-Myometrial Symposium. Los Angeles USA: 2002
Symposium: Scientific and clinical aspects of the management of premature labour: New Hall-University of Cambridge: 2002
Department of Obstetrics and Gynaecology, University of Leeds: 2003.
Action Research-North East Supporters Meeting-Newcastle upon Tyne: 2003
Action Research-Yorkshire Supporters Meeting-York: 2003
Institute of Reproductive and Developmental Biology (IRDB) - Imperial College Hammersmith Hospital Campus-University of London: 2004
NCBES-Symposium “Regulation of smooth muscle function in health and disease”- National University of Ireland at Galway: 2005.
BARTS ENDOCRINE CLUB- Department of Endocrinology-St. Bartholomew's Hospital-University of London: 2006
Action Medical Research-Yorkshire Supporters Meeting-York: 2006

HONOURS
Fetal Medicine Foundation Prize for Obstetric Research (£5,000) with Dr MWJ MacDougall and Professor SC Robson (2002)

Funding

1) The control of human myometrial activity during gestation: a role for Galphas in term and pre-term labour.
Action Research. With Dr A López Bernal 1994-1996 (S/P/2576) = £121,936
Post-Doctoral RAIIA

2) Regulation of Galphas protein isoform expression in human myometrium.
Tommy’s Campaign. Principal Investigator. 1998-2000 (Grant No.27) = £71,093
Post-Doctoral RAIA

3) Myometrial gene expression during human pregnancy: a cyclic AMP mediated process.
The Wellcome Trust. Principal Investigator. 1998-2001 (053563) = £200,661
Post-Doctoral RAIA (level 2) plus Grade D Research Technician

4) Regulation of Galphas and connexin-43 gene expression in the human myometrium: a role for the Sp transcription factor family.
The Wellcome Trust. Principal Investigator. 2000-2001 (058020) = £80,792
Post-Doctoral RAIA (level 2)

5) Control of alternative precursor mRNA splicing of Galphas in human myometrium during pregnancy and labour.
Action Research. Principal Investigator. 1998-2001 (S/P/3232) = £117,734
Post-Doctoral RAIA

6) Regulation of human myometrial gene expression by cyclic AMP related bZIP transcription factors.
The Wellcome Trust. Principal Investigator. 2001-2004 (062928) = £221,674
Post-Doctoral RAIIA (level 3) plus Grade D Research Technician

7) The expression of protein kinase A holoenzymes in human myometrium during pregnancy and labour.
Action Research. Principal Investigator. 2001-2003 (S/P/3689) = £93,569
Clinical Research Associate (Grade 5)

8) Expression of the CREM gene in the human myometrium: regulation by alternative pre-mRNA splicing.
The Wellcome Trust. Principal Investigator. 2002-2005 (066148) = £166,621
Post-Doctoral RAIIA (level 3)

9) Regulation of hCG/LH receptor gene expression in the human myometrium during pregnancy and labour.
Action Research. Principal Investigator. 2002-2004 (S/P/3766) = £85,412
Post-Doctoral RAIA

10) Regulation of the protein kinase A regulatory subunit RIIalpha gene in the human myometrium during pregnancy and labour.
Action Medical Research. Principal Investigator. 2004-2007 (S/P/3972) = £142,083
Post-Doctoral RAIIA

11) Uterine receptivity-the regulation of expression of histone deacetylase (HDAC)/DNA methyl transferase sensitive genes involved in myometrial quiescence during fetal maturation
Ph.D studentship for Mr Tamar Moussed Mahmoud Abou-Amara., Cultural Counsel of the Arab Republic of Egypt = £48,600

12)The role of histone deacetylases in regulating human myometrial activity during gestation
Society of Reproduction and Fertility.with Professor Alison Murdoch
Summer Vacation Scholarship for Mr Jamie Oughton 2007 = £1400

13)MRC(UK) with Dr NR Chapman (PI-Sheffield University), Dr DOC Anumba (Sheffield University) and Dr R Khan (Nottingham University) 2008-2011 (G0701322) = £447,201
Post-Doctoral RAIA

14)Novel regulation of human myometrial contractility by histone deacetylase 8 (HDAC8): the use of specific inhibitors as tocolytics
MRC (UK) Principal Investigator with Prof MJ Taggart, Dr M Karolczak-Bayatti and Prof SC Robson.
2008-2011 (G0800202) = £460,768
Post-Doctoral RAIA plus Grade D Research Technician

15) Validation of the guinea-pig as an appropriate model for human labour: HDAC inhibitors as tocolytics for preterm labour.
MRC (UK) Principal Investigator with Prof MJ Taggart, Dr NR Chapman (Sheffield), Prof BR Mitchell (Alberta, Canada) 2010-2012 (G0900525) = £228,024
Post-Doctoral RAIA

16) The novel regulation of blood vessel contractility by protein acetylation: the role of HDAC8.
BHF with Prof MJ Taggart (PI)
2010-2013 (PG/09/075) = £175,499
Post-Doctoral RAIA

Keywords

Human parturition, Myometrium, Gene Expression, Alternative Splicing, SAGE, SSH, Microarrays.

Undergraduate Teaching

Reproductive and Developmental Physiology PSC2015
MRes module PGY8003