Professor Mandy MacLean

  • Professor of Pulmonary Pharmacology (Institute of Cardiovascular and Medical Sciences)
  • Associate - Life Sciences (School of Life Sciences)

telephone: 01413304768
email: Mandy.MacLean@glasgow.ac.uk

Biography

Mandy's research has focused on the role of serotonin in the development of pulmonary arterial hypertension (PAH). More recently her work has focused on gender effects and interactions between serotonin and oestrogen metabolism in PAH. Awards include a Royal Society Wolfson Research Merit Award in 2010. She delivered the 2008 Estelle Grover lecture at the ATS Grover conference. In 2013 she was elected as a Fellow of The Royal Society of Edinburgh (FRSE), awarded the British Pharmacological Society AstraZeneca Prize for Women in Pharmacology and a Royal Society Leverhulme Trust Senior research Fellowship. She was Vice President (Meetings) of the British Pharmacological Society from 2007-2009. She has co-chaired a BBSRC grant committee and held committee roles within the American Thoracic Society (ATS). She is currently a member of the MRC Non-Clinical Training Panel, the BBSRC Industrial Case Assessment Panel and the BBSRC Skills and Careers Committee, having just Chaired the BBSRC Fellowship review. She is a currently member of the ATS Pulmonary Circulation Assembly Planning Committee. Mandy received an MBE in the 2010 Queen's New Years Honours list for her career and public engagement activities. She plays a key role in the University's public engagement agenda including running monthly events for Glasgow's Cafe Scientifique since 2004 (110 events). Mandy has always had a passion for postgraduate student training, having attracted over £4M for PhD and MRes opportunities and was appointed College Dean of Graduate Studies from 2010-2013. She also attracted and directed a £3M initiative to build capacity in in vivo skills funded by Pharma, UK Research Councils and HEI Funding Councils and holds advisory roles for in vivo science for the BBSRC, MRC and BPS. She was re4cently shortlisted for a WISE research award and was elected as an ordinary member of Council for the Royal Society of Edinburgh in 2015.

Research interests

Leader: Vascular Research

Prof Margaret (Mandy) R MacLean directs a research group studying the pharmacology of pulmonary arterial hypertension (PAH). The group has a particular interest in the role of serotonin in the pathobiology of pulmonary hypertension. More recently the group has been investigating why women get PAH more frequently than men and they have shown:


1.Oestrogen (E2)/sex-related suppression of BMPR2 signalling in human PASMCs (hPASMCs) derived from non-PAH women contributes to a pro-proliferative phenotype that may predispose women to PAH.


2. BMPR2 signalling is also reduced in the lungs of females but can be `rescued' in vivo by inhibition of E2 synthesis or blockade of the estrogen receptor alpha (ERα).


3. ERα is highly expressed in female human PASMCs (hPASMCs) from PAH patients and mediates E2-induced proliferation of hPASMCs via mitogen-activated protein kinase and Akt signalling. Serotonin increases ERα expression in hPASMCs and antagonism of ERα reverses serotonin-dependent pulmonary hypertension (PH) in the female mouse and increases BMPR2 expression.


4. Human pulmonary arteries can both synthesise E2 in the PASMCs via aromatase activity and metabolise E2 via CYP1B1. The unique phenotype (increased E2 synthesis and metabolism, decreased BMPR2 signalling) of female PASMCs facilitates the therapeutic effects of anastrozole (inhibits aromatase and therefore endogenous E2 synthesis and restores BMPR2 signalling) in experimental PH confirming a role for endogenous E2 in the disease pathogenesis in females, suggesting aromatase inhibitors may be therapeutic. Indeed, a clinical trial using anastrozole is ongoing in the USA.


5. CYP1B1 may provide a novel therapeutic target for PAH. Increased CYP1B1-mediated E2 metabolism promotes the development of PAH, likely via the formation of mitogens, including 16α-hydroxyestrone; serotonin increases CYP1B1 expression in hPASMCs. CYP1B1 also contributes to the development of dexfenfluramine-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro.


6. Mts1 over-expression combined with female gender is permissive to the development of experimental PAH in mice, mediated by the serotonin system.


7. Sex influences miRNA expression; E2 decreases miRNA-96 expression in female BMPR2 mutant PASMCs and PASMCs from female PAH patients. miRNA-96 regulates the 5HT1B-mediated prolifer

AstraZeneca Prize Lecture

Research:

Pharmacology of PAH
Pulmonary Hypertension
Click to view Prof MacLean's PhD studentship awards

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Investigating the role of IL-33/ST2 signalling in the cardiac and vascular remodelling associated with pulmonary arterial hypertension
    British Heart Foundation
    2017 - 2021
     
  • Sex and the development of pulmonary arterial hypertension
    British Heart Foundation
    2016 - 2021
     
  • Role of miR96 in Pulmonary Arterial Hypertension
    Medical Research Council
    2016 - 2019
     
  • Investigating oestrogen metabolism in pulmonary artery smooth muscle cells
    British Heart Foundation
    2016 - 2018
     
  • SUPPRESSION OF IL-6 TRANS-SIGNALLING BY BMP4:A MISSING LINK" IN THE DEVELOPMENT OF PULMONARY ARTERIAL HYPERTENSION?"
    British Heart Foundation
    2014 - 2017
     
  • Gender and the development of pulmonary arterial hypertension: regulation of genes from mouse to man
    British Heart Foundation
    2014 - 2016
     
  • BHF Centre of Excellence
    British Heart Foundation
    2014 - 2019
     
  • Targeting microRNA-96 for the treatment of pulmonary arterial hypertension.
    Medical Research Council
    2014 - 2015
     
  • Oestrogen synthesis and metabolism in pulmonary arterial hypertension
    British Heart Foundation
    2013 - 2016
     
  • Serotonin and oestrogen in pulmonary arterial hypertension
    Royal Society
    2013 - 2014
     
  • Excellence with Impact - Sparking Impact Award
    Biotechnology and Biological Sciences Research Council
    2013 - 2014
     
  • Development of MiR145 Antagonism as a novel Therapeutic strategy for Application to the treatment of pulmonary arterial hypertension.
    British Heart Foundation
    2013 - 2015
     
  • Gender and the development of pulmonary arterial hypertension: regulation of genes from mouse to man
    British Heart Foundation
    2011 - 2014
     
  • Probing the pharmacology of the 5-HT1B receptor and its role in pulmonary disease
    BBSRC
    2011 - 2012
     
  • Micro RNA and their role in vascular remodelling associated with the development of pulmonary arterial hypertension
    British Heart Foundation
    2011 - 2013
     
  • Wolfson Merit Award
    Royal Society
    2010 - 2015
     
  • Probing the pharmacology of the 5-HT1B receptor and its role in pulmonary disease
    BBSRC
    2009 - 2010
     
  • BBSRC in vivo Mammalian Biology Workshop 1-2 October 2009
    BBSRC
    2009 - 2009
     
  • Pulmonary Hypertension in Lupus
    Arthritis Research Campaign
    2009 - 2010
     
  • Effect of oestrogen on the serotonin system: role in the development of pulmonary hypertension
    MRC
    2009 - 2011
     
  • Cafe Scientifique
    Scottish Government
    2008 - 2009
     
  • IMB Launch
    Pfizer Limited
    2008 - 2008
     
  • The role of endothelial tryptophan hydroxylase in pulmonary vascular remodelling: an integrated approach
    BBSRC
    2008 - 2010
     
  • The role of endothelial tryptophan hydroxylase in pulmonary vascular remodelling: an integrated approach
    Novartis Pharmaceuticals
    2007 - 2012
     
  • Selective serotonin-reuptaker inhibitors, (SSRIs) and the risk of persistant pulmonary hypertension on the newborn
    Tenovus-Scotland
    2007 - 2008
     
  • Capacity Building Award in Integrative Mammalian Biology
    BBSRC
    2006 - 2012
     
  • Interactions between mts 1 and serotonin in vascular remodelling
    BBSRC
    2006 - 2009
     
  • PULMONARY HYPERTENSION: Functional Genomics and Therapy of Lung Vascular Remodelling
    European Commission
    2006 - 2009
     
  • Interactions between mts 1 and serotonin in vascular remodelling
    British Pharmacological Society
    2006 - 2008
     
  • Engaging Science People Award: Cirque du Science
    Wellcome Trust
    2005 - 2006
     
  • Interactions between serotonin transport inhibitors and 5-ht1B receptors in pulmonary arteries
    British Heart Foundation
    2005 - 2007
     
  • Do interactions between 5-HT and BMPR-II systems determine susceptibility to pulmonary hypertension?
    British Heart Foundation
    2004 - 2006
     
  • Mice overexpressing the 5HT transporter gene: a new model of Pulmonary Hypertension?
    British Heart Foundation
    2003 - 2006
     
  • Pulmonary Vascular MechanismsUnderlying Genetic Susceptibility to Pulmonary Hypertension in the Fawn-Hooded Rat
    British Heart Foundation
    2002 - 2004
     
  • Effects of acute and chronic hypoxia on cells derived from the pulmonary and systemic circulations
    North Glasgow Hospitals University NHS Trust
    2001 - 2001
     
  • 5-hydroxytryptamine (5-HT) moduline: influence on pulmonary vascular responses to 5-HT
    MRC
    2001 - 2002
     
  • Pharmacological synergy: role in pulmonary hypertension
    Wellcome Trust
    2000 - 2003
     
  • Adenovirus-Mediated Gene Transfer of Endothelial Nitric Oxide Synthase (eNOS) in experimental Models of Left and/or Right Ventricular ...
    National Heart Research Fund
    1999 - 2000
     
  • 5-Hydroxytryptamine 1B receptors: role in pulmonary hypertension
    Wellcome Trust
    1999 - 2001
     

Teaching

Professor MacLean delivers Level 1 Biology lectures on the cardio-respiratory system, supervises Level 4 projects and Masters projects.

Additional information

Editorial Board

  • 2009 - ongoing: Faculty 1000 - Biology, Section Head, Respiratory Pharmacology
  • 2008 - ongoing: Current Opinion in Pharmacology - Section Editor, Respiratory Section
  • 1999 - 2003: British Journal of Pharmacology
  • 1999 - ongoing: Pulmonary Pharmacology & Therapeutics

Grant Advisory Board

  • 2013 - ongoing: BBSRC - Deputy Chair, Industrial CASE PhD Panel
  • 2013 - ongoing: BBSRC - Bioscience Skills & Careers Committee
  • 2013 - ongoing: MRC - Non-Clinical Training Panel
  • 2010 - ongoing: BBSRC - Animals Advisory Group
  • 2009 - 2010: BBSRC - Member of Strategic LoLa Committee
  • 2009 - 2012: BBSRC - Deputy Chair, Grant Committee A
  • 2007 - ongoing: BBSRC - Member of BBSRC Animal Physiology Working Group
  • 2007 - 2009: BBSRC - Member of Animal Sciences Committee
  • 2004 - ongoing: IUPHAR - Nomenclature Committee for Urotensin-II

Invited International Presentations

  • 2016: American Thoracic Society (ATS), San Francisco - Scientific symposium speaker
  • 2016: Pulmonary Vascular Research Institute (PVRI), Rome - Two oral presentations (invited). Leading new task force and symposium.
  • 2015: British Pharmacological Society Conference, London - Symposium speaker (invited)
  • 2015: 9th International Young Investigators Symposium on Smooth Muscle in Airways and Vascular Disease, London - Speaker (invited)
  • 2015: 10th International Workshop on Cardiovascular Biology and Translational Medicine, London - Speaker (invited)
  • 2015: ATS Grover Conference, Colorado, USA - Speaker (invited)
  • 2015: Dundee Discovery Unit, Dundee, UK - Presentation
  • 2015: MiRagen Therapeutics, Boulder, USA - Presentation by phone
  • 2015: Vienna - Drug induced Pulmonary Hypertension Workshop, International Symposium, speaker (invited)
  • 2015: Dundee Medical School, Dundee, UK - Speaker (invited)
  • 2015: American Thoracic Society (ATS), Denver, USA - Three poster presentations
  • 2015: PVRI, Guangzhou, China - Plenary speaker and discussion chair (invited)
  • 2015: China Agricultural University, Beijing, China - Seminar (invited)
  • 2014: British Pharmacological Society Conference, London, UK - Prize Lecture (AstraZeneca prize for women in pharmacology), two posters and one short talk.
  • 2014: European Respiratory Society, Munich, Germany - Oral presentation
  • 2014: Glaxo Smith Kline, Stevenage, UK - Presentation (secured iCASE award)
  • 2014: 9th John Vane Memorial Symposium on Prostacyclin Science and Pulmonary Vascular Disease, London - Speaker (invited)
  • 2014: Royal Society - 9th John Vane Memorial Symposium
  • 2013: Keystone meeting on pulmonary vascular disease and right ventricular dysfunction - Co-organiser, Chair, speaker
  • 2013: ATS mini-symposium, Philadelphia, USA - Organiser, Speaker and Chair.
  • 2013: ATS 2013 - Co-organiser of mini-symposium 'Gender and pulmonary hypertension'
  • 2012: Monterey, California, USA - Co-organiser of 2012 Keystone meeting on pulmonary hypertension
  • 2012: ATS, San Francisco, USA - Speaker (invited)
  • 2012: London, UK - 7th John Vane Memorial Symposium on Prostacyclin Science and Pulmonary Vascular Disease - Speaker (invited)
  • 2012: Royal Society - 7th John Vane Memorial Symposium
  • 2012: London, UK - 7th International Workshop on Cardiovascular Biology - Speaker (invited)
  • 2011: American Heart Association, Orlando, USA - Three presentations
  • 2011: ATS Grover Conference, Colorado, USA - Risk factors in PAH: Chief Organiser, Chair, Presenter
  • 2011: 12th International Workshop on Scleroderma Research 2011
  • 2010: Colorado, USA - Keystone Symposium on Hypoxia: Molecular Mechanisms
  • 2008: Colorado, USA - Grover Conference on PAH. Winner of Estelle Grover Award and Plenary Lecturer. http://www.thoracic.org/sections/about-ats/assemblies/pc/grover.html
  • 2008: Orange County, California, USA - 4th World Symposium on Pulmonary Hypertension. Working Group Member and Presenter on the Serotonin Hypothesis. Basic Science - Cellular & Molecular Basis of PAH
  • 2008: The Royal Society, London, UK - Invited Speaker - Third John Vane Memorial Symposium - Prostacyclin Science and Pulmonary Vascular Disease
  • 2007: San Francisco, California, USA - American Thoracic Society Congress. Speaker and Chair on Mini-symposium 'Cellular and molecular mechanisms of pulmonary hypertension: new insights'
  • 2007: Nice, France - 12th Annual Meeting of the European Council for Cardiovascular Research. Keynote Speaker: Pulmonary Hypertension
  • 2007: Crieff, Scotland - James Black Conference on 'Cutting Edge Concepts in Lung Pharmacology'. Co-organiser, chair and speaker
  • 2007: Leeds, England - Meeting of Cafe Scientifique Organisers - Leading panel discussion with Lord Rees (Royal Society) and Daniel Glaser Wellcome Trust)
  • 2007: London, England - 1st International Meeting on Pulmonary Hypertension in Childhood. Invited Speaker. Royal College of Physicians
  • 2006: San Diego, California, USA - Invited speaker at American Thoracic Society International Conference - Postgraduate Course on 'Cellular Biology of Hypoxia'. 'highlighted abstract' awarded.
  • 2006: Phuket, Thailand - Annual meeting of the Pharmacological and Theraputic Society of Thailand - 13th Dr. Chiravat's Memorial Lecture
  • 2006: Prague, Czech Republic - Physiological Society International Workshop on 'Cardiopulmonary Function in Health and Disease'
  • 2006: Dublin, Ireland - The Associations of Pulmonary Hypertension Centres of Great Britain and Ireland - Speaker at 2nd International Workshop on pulmonary hypertension
  • 2005: European Respiratory Society - Scientific Year in Review. This symposium presents some of the major advances in understanding the biological and molecular mechanisms underlying respiratory disorders. Title of talk: Serotonin transporter genes, pulmonary haemodynamics and pulmonary hype
  • 2005: American Thoracic Society - Oral presentation
  • 2004: Baltimore, Maryland, USA - The Pulmonary vasculature in lung diisease (6 speakers) American Pulmonary Research Group
  • 2004: Orlando, Florida, USA - Presenter of two talks at mini-symposium on the interactions between serotonin and the BMPR2 system. (6 speakers) American Thoracic Society
  • 2004: American Thoracic Society - Two selected oral presentations
  • 2004: Philadelphia, Pennsylvania, USA - Johnson and Johnson, USA. Spring House Seminar (1 speaker)

Prizes, Awards and Distinctions

  • 2013: Fellow of the Royal Society of Edinburgh (FRSE)
  • 2013: Royal Society - Leverhulme Senior Fellowship
  • 2013: British Pharmacological Society - Astrazeneca Prize for Women in Pharmacology
  • 2010: College of MVLS - Ongoing Dean of Graduate Studies
  • 2010: MBE for Services to Science
  • 2010: BBSCR Masters Studentships Priority Area Training Awards. PI on application from Faculty of Biomedical and Life Sciences for integrative in vivo biology/systems biology training. Awarded 15 MRes studentships. 2010-2013
  • 2010: Royal Society Wolfson - Research Merit Award for research into the role of serotonin in pulmonary hypertension
  • 2009: BBSRC Deputy Chair Grant Committee A
  • 2009: MRC Capacity Building Studentship Competition 2009 and 2010. PI on application from Faculty of Biomedical and Life Sciences and Faculty of Medicine for in vivo training. Awarded 6 x 1+3 PhD studentships: £493,860
  • 2008: Estelle Grover Lecture Award - Awarded by the American Thoracic Society in recognition of international contribution to research into pulmonary arterial hypertension
  • 2006: Principle Investigator on Capacity Building consortium training award in Integrative Mammalian Biology awarded to Glasgow/Strathclyde University. £2.9M (Funded by Pfizer, GSK, AstraZenica, BPS, DTI, BBSRC and MRC), 2006-2011.
  • 2005: Elected Fellow of British Pharmacological Society (F.B.Pharmacol.S.) in recognition of commitment and distinction in Pharmacology through scholarship and service to the Society.

Professional Learned Society

  • 2006 - 2008: British Pharmacological Society - Vice-President (Meetings)
  • 2001 - ongoing: American Thoracic Society - -member of 'pulmonary circulation programme committee' and 'pulmonary circulation planning committee'
  • 2001 - ongoing: International Union of Pharmacology - Receptor Nomenclature Committee
  • 2000 - ongoing: American Heart Association - Communications Committee 2000-03.
  • 1998 - ongoing: European Respiratory Society
  • 1992 - ongoing: British Society for Cardiovascular Research - Member
  • 1991 - ongoing: Physiological Society - Member
  • 1988 - ongoing: British Pharmacological Society - Meetings Committee 2001-06. Scientific Interest Group on Cardiovascular and Pulmonary Pharmacology 2003-ongoing.

Publications

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