Personal profile

Overview

Ann runs a research lab which focusses on elucidating the molecular and cellular mechanisms underpinning vascular calcification. Her research is currently supported by grants from the British Heart Foundation. She has published over 50 scientific papers and has received many invitations to present her work at National and International conferences. She has trained 20 PhD students, 11 Masters students and 1 MD student and has examined over 28 PhD and Masters theses. Ann is a member of the Heart Research UK Translation Research Grants Panel, was a member of the Biomolecular Medicine & Therapeutics Panel, Science Foundation Ireland (until 2010), and was an elected committee member for the British Society of Matrix Biology with a responsibility for bursaries (2007 - 2010). She reviews manuscripts and grants for several International journals and funding agencies, respectively. Ann is the Director for Progression on the MB ChB Programme, and was formerly the Undergraduate Teaching Lead in the Institute of Cardiovascular Sciences, the Lead for PBL in Years 1 and 2 of the MB ChB Programme, and a member of the Education Management Team in FLS. She was Director of the Medical Biochemistry degree programme (2001-2008), and currently interviews prospective undergraduate students in medicine and biological sciences and teaches on several undergraduate courses run by the Schools of Biological Sciences and Medical Sciences.

Biography

Ann is a member of the Division of Cardiovascular Sciences at The University of Manchester.

She graduated with a degree in Biochemistry from Manchester and then completed a PhD under the supervision of Professor Michael Grant at the University. Her post-doctoral studies took her to the Paterson Institute for Cancer Research. She was then awarded a Wellcome Trust Junior Research Fellowship and joined the Wellcome Trust Centre for Cell-Matrix Research in 1993. Ann was appointed a Lecturer in the Faculty of Medical and Human Sciences in 1996, Senior Lecturer in 2000, Reader in 2007 and Professor of Vascular Cell Biology in 2010.

Research interests

The primary focus of Ann's reserach is to elucidate the molecular and cellular mechanisms regulating pathological vascular calcification, which is highly correlated with increased morbidity and mortality in patents with atherosclerosis, diabetes and end-stage renal disease.  Her group was the first to demonstrate that vascular pericytes may be involved in this process as she demonstrated that these cells can differentiate along several lineages including osteogenic, chondrogenic and adipogenic in response to specific stimuli. She has now confirmed that vascular smooth muscle cells (VSMC) can also undergo osteogenic differentiation and deposit a mineralised matrix. Using both pericytes and vascular smooth muscle cells, she has demonstrated that the Wnt- and TGFbeta-signaling pathways are master controllers of differentiation and that they also contribute to the pathogenesis of vascular calcification. In addition, she has discovered other novel inhibitors of vascular calcification including TSG-6, CaR, Axl and its ligand, Gas6 and HtrA1 (a serine protease with the ability to regulate TGFbeta signalling). Therefore, current research aims to determine the mechanisms by which these signaling pathways regulate pericyte and VSMC differentiation and vascular calcification. Ultimately, these studies should enable us to develop approaches to (a) prevent pathological calcification, and (b) manipulate cells along VSMC lineages for therapeutic tissue regeneration.

Teaching

Undergraduate:

Director for Progression, MB ChB Programme

PBL Tutor, Cardiorespiratory Fitness Module, MB ChB programme

Member of exams team, Cardiorespiratory Fitness Module, MB ChB programme

OSCE examiner, Years 1 and 2, MB ChB programme

PEP supervisor, Year 2, MB ChB programme

Lecturer, Biochemical Basis of Disease (BIOL31332)

Supervisor of dissertations and final year projects, Schools of Biological Sciences and Medical Sciences

Post-graduate:

Ann has supervised 20 PhD, 12 Masters and 1 MD students to completion. She has examined 27 PhD and 1 MD theses (16 internal and 12 external) and is a member of the Manchester BHF 4 year PhD programme committee. Ann currently co-supervises 2 PhD students with Professor Martin Humphries and Dr Donald Ward. 

Ann would welcome enquiries from students wishing to study for a higher research degree in the general area of vascular cell biology. For further information, see: Postgraduate opportunities.

My collaborations

  • Prof Keith Brannan, Division of Molecular and Clinical Cancer Sciences
  • Dr Jacqui Ohanian, Division of Cardiovascular Sciences
  • Dr Cathy Holt, Division of Cardiovascular Sciences
  • Dr Nick Ashton, Division of Cardiovascular Sciences
  • Prof Sheila Francis, University of Sheffield

 

Memberships of committees and professional bodies

  • British Society of Matrix Biology
  • British Atherosclerosis Society

Methodological knowledge

  • Analysis of vascular calcification in vitro, ex vivo and in vivo
  • Isolation, culture & analysis of primary vascular cells (endothelial cells, pericytes, smooth muscle cells); culture of established cell lines
  • In vitro differentiation models (osteogenic, chondrogenic and adipogenic)
  • 3-D and 2-D cell culture models; general cell biology assays (apoptosis, adhesion, signalling etc)
  • Modulation of gene expression using recombinant adenoviruses, lentiviruses and siRNA

Qualifications

  • BSc (Hons), Biochemistry, 1st Class, University of Manchester
  • PhD, University of Manchester

Social responsibility

Lead for Public Engagement, Division of Cardiovascular Sciences

Research interests

Molecular and Cellular mechanisms underpinning Vascular Calcification

Vascular calcification is a common complication of many diseases including atherosclerosis, diabetes, renal disease, hypertension, vein graft failure and calciphylaxis. Recent studies have shown that there is a strong association between the presence of vascular calcification and adverse clinical events such as myocardial infarction and stroke. However, little is known about how the deposition of mineral in vessels is controlled. We have shown that vascular pericytes have multi-lineage potential and can differentiate into osteoblasts and chondrocytes in vitro and in vivo. We have also shown that these cells can deposit a calcified matrix resembling that found in calcified atherosclerotic plaques, suggesting that pericytes may mediate, at least in part, vascular calcification. We have recently demonstrated that several genes that are implicated in the pathological calcification of arteries, namely matrix Gla protein, Axl receptor tyrosine kinase and HtrA1 serine protease are all differentially expressed during pericyte differentiation. We are currently using molecular, cellular and biochemical approaches to elucidate the mechanisms by which each of these proteins regulates calcification. In time, this integrated programme of research will provide important insights into the pathogenesis of vascular calcification and may identify potential targets for the therapeutic manipulation of this event.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

Research Beacons, Institutes and Platforms

  • Manchester Regenerative Medicine Network
  • Christabel Pankhurst Institute

Keywords

  • Vascular calcification

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