Neuroscience at Nottingham
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Image of Lopa Leach

Lopa Leach

Associate Professor of Anatomy & Vascular Biology, Director (Strategy) for PGR, Faculty of Medicine & Health Sciences

Contact

  • workRoom E176a The University of Nottingham Medical School
    Queen's Medical Centre
    Nottingham
    NG7 2UH
    UK
  • work0115 82 30175
  • fax0115 82 30142

Biography

please see above.

Teaching Summary

Vascular Biology, Human Anatomy, Reproductive System, Renal Physiology, Diagnostic Imaging and Interpretation, Defects in Development

Research Summary

Interests

  • Placental Vascular dysfunction in pregnancies complicated by diabetes (Type 1, diet and metformin treated GDM)
  • Angiogenic growth factors in pre-eclampsia and vasscular dysfunction
  • Molecular mechanisms underlying physiological vasculogenesis and angiogenesis.
  • Endothelial barrier function
  • Role of VE-cadherin, beta-catenin, occludin in pathological angiogenesis and vascular permeability.
  • MRI and Mathematical modelling of maternal and fetal blood flow in the placenta
  • Role of Human Mesenchymal stem cells in vascular barrier integrity
  • Epigenetic regulation of the human placental barrier

Techniques

  • Ex vivo perfusion of human placental vascular beds.
  • In vitro modelling of endothelial angiogenesis.
  • In vitro modelling of barrier function.
  • Confocal imaging of junctional proteins.
  • Tissue culture of primary human endothelial, endothelial progenitor and epithelial cells.
  • Immunocytochemistry, Immunoblotting, electron microscopy,real time imaging.

Projects

  • Mathematical Modelling of Flow in the human placenta
  • Vascular dysfunction in the human diabetic placenta: molecular mechanisms behind angiogenesis, permeability changes and inflammation.
  • Angiogenic growth factors in pre-eclampsia (British Heart Foundation)
  • Fetal endothelial cells and barrier changes in vitro
  • Transmigration of human umbilical mesenchymal stem cells
  • Regulation of placental vascular tone

Local Collaborators

  • Professor Dave Bates (Pre-clinical Oncology)
  • Dr Nia Jones (Academic Obstetrics)
  • Professor Penny Gowland (Physics)
  • Dr Paul Brownbill and Dr Igor Chernyavasky (Univ of Manchester)
  • Dr Vera Ralevic (Life Sciences)
  • Dr Billy Dunn (Life Sciences)

International Collaborators

  • Professor Henning Schneider, University of Berne, Switzerland
  • Dr K Juuti-Uustilo, University of Tampere, Finland

Recent Publications

Past Research

Junctional Complexes in the human Placenta (Wellcome Trust)

The diabetic human placenta (Wellcome Trust)

In vitro model of the outer retinal barrier (Wellcome Trust)

Mathematical modelling of placental flow (MRC; EU)

Angiogenesis and junctional adhesion molecules (AICR)

Molecular mechanisms behind endothelial dysfunction (Anatomical Society)

Angiogenic growth factors and placental function in Pre-eclampsia (British Heart Foundation)

Future Research

Impairment in vascular function, specifically increased angiogenesis and vascular leakage, is a major complication of diseases such as diabetes, cancer and hypertension. The adhesion molecules which hold the lining cells i.e. the endothelial cells together play a role in both these functions. Our group uses ex vivo human perfusion models and in vitro cell cultures to understand the signalling and regulation (gene and protein) of these molecules and how they may go wrong, specially in diabetes. Our major interest is the functioning of blood vessels in the human placenta, in normal pregnancies and those complicated by diabetes and pre-eclampsia. The placenta is vital for fetal nutrition, development, growth and well-being throughout gestation and impaired placental function causes fetal morbidity and mortality. Moreover, in-utero disturbances may lead to fetal programming and increased risk of cardiovascular diseases and diabetes in adulthood. We wish to develop therapeutic strategies to prevent the vascular complications we have shown to exist in the placenta in pregnancies complicated by diabetes. We have a near-physiological, extra-corporeal placental perfusion system which allows us to look at the effect of key factors on trans-placental transport, whilst in vitro models allow more long term effects on angiogenic parameters to be studied. The placental perfusion system allows monitoring of maternal and fetal blood flow and pressure and lends itself to studies of directional transport. We have expertise into growth of primary endothelial cells in 2-D or 3-D culture systems to study barrier properties and angiogenesis. We have a trilayer model of the outer retinal barrier which allows studies into drug transport as well as hypoxia-mediated neo-vascularisation. Immunocytochemistry, confocal microscopy and real time imaging, as well as standard molecular biology which include immunoblotting and transfection studies are routinely used in our laboratory. We also have expertise of immuno-electron methods and transmission electron microscopy. The growth factors of specific interest to us include vascular endothelial growth factor and angiopoietin-1. We have knowledge of the behaviour of junctional adhesion molecules (occludin, VE-cadherin and beta-catenin) in regulating paracellular permeability, endothelial survival and angiogenesis.

We are interested in the potential use of human mesenchymal stem cells from the umbilical cord in vascular repair. Research is on going using real time imaging and other laboratory cell biology techniques.

Neuroscience at Nottingham

The University of Nottingham
Address line two
Nottingham, postcode


telephone: +44 (0) 115 XXX XXXX
email: research-group-email@nottingham.ac.uk