海角黑料

Contact

• workRoom E71 The 海角黑料 Medical School
  Queen's Medical Centre
  Nottingham
  NG7 2UH
  UK
• work0115 82 30175
• fax0115 82 30142
• lopa.leach@nottingham.ac.uk

Biography

please see above.

Teaching Summary

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

Research Summary

Interests

• Maternal venous return from the placenta and the effect of placental and uterine contractions as potential markers of stillbirth
• Placental Vascular dysfunction in pregnancies complicated by diabetes (Type 1, Type 2, GDM - diet and metformin treated)
• Angiogenic growth factors, endoglin, glycocalyx in pre-eclampsia and vascular 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 in normal and gestational diabetes, effects of endoglin silencing
• Health Inequality and Race

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 cells, mesenchymal stem cells, endothelial progenitor and epithelial cells.
• Immunocytochemistry, Immunoblotting, electron microscopy,real time imaging.

Projects

• Role of Maternal venous return from the placenta in oxygen transport to the fetus using ex vivo and MRI analyses (Welcome-Leap)
• Mathematical Modeling of Flow, venous return and oxygenation in the human placenta (Welcome-Leap
• 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, lineage commitment changes and control of endothelial integrity from sub-endothelial niches in normal pregnancies and those complicated by diabetes

Local Collaborators

• Professor Dave Bates, Dr Andy Benest (Pre-clinical Oncology)
• Dr Nia Jones/ Prof Kate Walker (Academic Obstetrics)
• Professor Penny Gowland (Physics)
• Professor Paul Hudson,Hubbard and Dr O'Dea (Mathematics)
• Prof Barrie Hayes-Gill, Prof Steve Morgan (Engineering)
• Dr Paul Brownbill and Dr Igor Chernyavasky (Univ of Manchester)

International Collaborators

W-L performers In Utero.

Selected Publications

• VILLOTA, S. D., TOLEDO-RODRIGUEZ, M. and LEACH, L., 2021. Diabetologia. 64(1), 195-210
• DELLSCHAFT, N. S., HUTCHINSON, G., SHAH, S., JONES, N. W., BRADLEY, C., LEACH, L., PLATT, C., BOWTELL, R. and GOWLAND, P. A., 2020. PLoS Biol. 18(5), e3000676

• View all 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, materno-fetal oxygen transfer, 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. Our recent interest is a team science one (Physiologists, clinicians, mathematicians, engineers, physicists, computer scientists) which looks at venous return and placental contractions as potential markers of still birth.

• SAMAR SALEM and LOPA LEACH, 2024. Clinical Science. 138, 87-102
• VILLOTA, S. D., TOLEDO-RODRIGUEZ, M. and LEACH, L., 2021. Diabetologia. 64(1), 195-210
• DELLSCHAFT, N. S., HUTCHINSON, G., SHAH, S., JONES, N. W., BRADLEY, C., LEACH, L., PLATT, C., BOWTELL, R. and GOWLAND, P. A., 2020. PLoS Biol. 18(5), e3000676
• BOARDMAN R, PANG V, MALHI N, LYNCH AP, LEACH L, BENEST AV, BATES DO and MACHADO MJC, 2019. American journal of physiology. Heart and circulatory physiology. 316(5), H1065-H1075
• RAZAK AA, LEACH L and RALEVIC V, 2018. Diabetes & vascular disease research. 15(6), 528-540
• PANG V, BATES DO and LEACH L, 2017. Clinical Science. 131(23), CS-2017-1252
• PANG, VINCENT, BATES, DAVID O. and LEACH, LOPA, 2017. PLACENTA. 57, 313-313
• VILLOTA, STEPHANY, LEACH, LOPA and TOLEDO-RODRIGUEZ, MARIA, 2017. PLACENTA. 57, 302-302
• ACHARYA G, APLIN J, BROWNBILL P, BULMER J, BURTON G, CHAMLEY L, CHERNYAVSKY I, CLARK A, COLLINS S, COTTRELL E, DILWORTH M, ELAD D, FILOCHE M, HANNAN N, HEAZELL AEP, JENSEN O, JOHNSTONE ED, LEACH L, LEWIS R, MORGAN T, MYERS J, NYE G, OYEN M, SALAFIA C, SCHNEIDER H and O'TIERNEY-GINN P, 2017. Placenta. 64 Suppl 1, S4-S8
• BROWNBILL P, CHERNYAVASKY I, BOTTALICO B, BOTTALICO B, DESOYE G, HANSSON S, KENNA G, KNUDSEN LE, MARKERT UR, POWLES-GLOVER N, SCHNEIDER H and LEACH L, 2016. Reproductive toxicology (Elmsford, N.Y.). 64, 191-202
• EBRAHIM NA and LEACH L, 2016. Placenta. 48, 87-98
• EBRAHIM N and LEACH L, 2015. Stem cells and development. 24(4), 426-436
• ABUMAREE MH, ALAHARI S, ALBRECHT C, AYE ILMH, BAINBRIDGE S, CHAUVIN S, CLIFTON VL, DESOYE G, ERMINI L, GIUFFRIDA D, GRAHAM CH, HUANG Q, KALIONIS B, LAGER S, LEACH L, LI Y, LITVACK ML, NUZZO AM, MORETTO-ZITA M, O'TIERNEY-GINN P, POWELL T, ROLFO A, SALOMON C, SEROV A, WESTWOOD M, YUNG HW and LASH GE, 2014. Placenta. 35 Suppl, S4-9
• LEACH L, HAMILTON RD and FOSS AJE, 2012. The British journal of ophthalmology. 96(8), 1152
• BULMER JN, BURTON GJ, COLLINS S, COTECHINI T, CROCKER IP, CROY BA, CVITIC S, DESFORGES M, DESHPANDE R, GASPEROWICZ M, GROTEN T, HAUGEN G, HIDEN U, HOST AJ, JIRKOVSK脕 M, KISERUD T, K脰NIG J, LEACH L, MURTHI P, PIJNENBORG R, SADEKOVA ON, SALAFIA CM, SCHLABRITZ-LOUTSEVITCH N, STANEK J, WALLACE AE, WESTERMEIER F, ZHANG J and LASH GE, 2012. Placenta. 33 Suppl, S9-S14
• CHERNYAVSKY, I.L., LEACH, L., DRYDEN, I.L. and JENSEN, O.E., 2011. Philosophical Transactions of the Royal Society. A, Mathematical, Physical, and Engineering Sciences. 369(1954), 4162-4182
• LEACH L, 2011. Microcirculation (New York, N.Y. : 1994). 18(4), 263-9
• LEACH L and MANN GE, 2011. Microcirculation (New York, N.Y. : 1994). 18(4), 253-5
• HAMILTON, R.D. and LEACH, L., 2011. . In: NAG, S., ed., The blood-brain and other neural barriers: reviews and protocols 686. Humana Press. 401-416
• SOUADKIA, N., BROWN, A., LEACH, L. and PRITCHARD, D.I., 2010. American Journal of Tropical Medicine and Hygiene. 83(3), 549-558
• CHERNYAVSKY, I.L., JENSEN, O.E. and LEACH, L., 2010. Placenta. 31(1), 44-52
• LEACH, LOPA and MAYHEW, TERRY M, 2009. Journal of anatomy. 215(1), 1-2
• LEACH, LOPA, TAYLOR, ALICE and SCIOTA, FLAVIA, 2009. Journal of anatomy. 215(1), 69-76
• PLANT, S. D., GRANT, D. M. and LEACH, L., 2007. Materials Letters. 61(14-15), 2864-2867
• HAMILTON, R.D., FOSS, A.J. and LEACH,L., 2007. Blackwell Synergy. Available at: <http://dx.doi.org/10.1111/j.1469-7580.2007.00812.x>
• RUTLAND, C.S., LATUNDE-DADA, A.O., THORPE, A., PLANT, R., LANGLEY-EVANS, S. and LEACH, L., 2007. Placenta. 28(7), 734-742
• BEBB,J., LEACH,L., ZAITOUN,A., HAND,N., LETLEY,D., THOMAS,R. and ATHERTON,J., 2006. Available at: <http://dx.doi.org/10.1136/jcp.2006.036772>
• LEACH, L., BADET, J., BROWNBILL, P., HARRIS, L., KEOGH, R., KALIONIS, B. and WHITLEY, G., 2006. Placenta. VOL 27(SUPP/A), S26-S29
• PLANT, S.D., GRANT, D.M. and LEACH, L., 2005. Biomaterials. 26(26), 5359-5367
• LEACH,L. and MAYHEW,T., 2005. Vasculogenesis and Angiogenesis in the diabetic placenta. In: IVANISEVIC, I, ed., Diabetology of Pregnancy Karger, S. AG, Basel, CHE.
• LEACH,L., 2005. Inter-endothelial junctions and Barrier Integrity.. In: PATTERSON, CAROLYN, ed., Perspectives on Lung Endothelial Barrier Function Elsevier Science BV, Amsterdam.
• LEACH, L., GRAY, C., STATON, S., BABAWALE, M.O., GRUCHY, A., FOSTER, C., MAYHEW, T.M. and JAMES, D.K., 2004. Diabetologia. 47(4), 695-709
• WILLIS, C.L., LEACH, L., CLARKE, G.J., NOLAN, C.C. and RAY, D.E., 2004. Glia. 48(1), 1-13
• DYE, J, LAWRENCE, L, LINGE, C, LEACH, L, FIRTH, J and CLARK, P, 2004. Endothelium. 11(3-4), 151-67
• WRIGHT, T.J., LEACH, L., SHAW, P.E. and JONES, P, 2002. Experimental Cell Research. 280(2), 159-168
• LEACH, L., BABAWALE, M.O., ANDERSON, M. and LAMMIMAN, M., 2002. Journal of Vascular Research. 39(3), 246-259
• LEACH, L. and DAVIES, D. C., 2002. Journal of Anatomy. VOL 200(PART 6), 539-540
• LEACH, L., 2002. Journal of Anatomy. VOL 200(PART 6), 599-606
• DYE, J F, LEACH, L, CLARK, P and FIRTH, J A, 2001. Microvascular Research. 62(2), 94-113
• DYE, J F, JABLENSKA, R, DONNELLY, J L, LAWRENCE, L, LEACH, L, CLARK, P and FIRTH, J A, 2001. Placenta. 22(1), 32-43
• BABAWALE, M O, LOVAT, S, MAYHEW, T M, LAMMIMAN, M J, JAMES, D K and LEACH, L, 2000. Diabetologia. 43(9), 1185-96
• DANTZER, V., LEACH, L. and LEISER, R., 2000. Placenta. VOL 21(SUPP/A), S69-S70
• MAYHEW, T. M., LEACH, L., MCGEE, R., WAN ISMAIL, W., MYKLEBUST, R. and LAMMIMAN, M. J., 1999. Placenta. VOL 20(NUMBER 5/6), 407-422
• LEACH,L., FIRTH,J.A., DYE,J.F. and CLARK,P., 1997. Human placental endothelium expresses an unusual phenotype Journal of Anatomy. 191, 142
• LEACH, L and FIRTH, J A, 1997. Microscopy Research and Technique. 38(1-2), 137-44
• LEACH,L., FIRTH,J.A., DYE,J.F. and CLARK,P., 1997. The regulation of cell adhesion molecules in human microvascular endothelial cells by the cAMP pathway Placenta. 18(5-6), A21
• LEACH,L., LAMMIMAN,M.J. and HOBSON,S., 1997. The cadherin-catenin complex in normal and histamine-perfused microvessels of the human term placenta - a confocal study International Journal of Microcirculation Clinical and Experimental. 17(4), 212
• LAMMIMAN,M.J. and LEACH,L., 1997. The cadherin-catenin complex in placental vessels - a confocal analysis Placenta. 18(5-6), A35
• FIRTH, J. A. and LEACH, L., 1997. Structure and Permeability in Human Placental Capillaries - A Review Trophoblast Research. VOL 9/10, 10-205-10-214
• LEACH,L., FIRTH,J.A., DYE,J.F. and CLARK,P., 1997. Human placental microvascular endothelial cells show distinct morphological responses to gels of type 1 collagen and matrigel Journal of Anatomy. 191, 136
• LEACH,L., FIRTH,J.A., DYE,J.F. and CLARK,P., 1997. Distinct morphological responses of endothelial cells to extracellular matrix gels in vitro International Journal of Microcirculation Clinical and Experimental. 17(4), 201-2
• FIRTH, J. A. and LEACH, L., 1996. Placenta. VOL 17(NUMBER 2/3), 89-96
• LEACH, L. and FIRTH, J. A., 1996. Reproduction, Fertility and Development. VOL 7(NUMBER 6), 1451-1456
• GALUSTIAN, C, DYE, J, LEACH, L, CLARK, P and FIRTH, J A, 1995. Actin cytoskeletal isoforms in human endothelial cells in vitro: alteration with cell passage. In Vitro Cellular and Developmental Biology: Animal. 31(10), 796-802
• LEACH, L, EATON, B M, WESTCOTT, E D and FIRTH, J A, 1995. Microvascular Research. 50(3), 323-37
• LEACH, L., BHASIN, Y., CLARK, P. and FIRTH, J., 1994. Placenta. VOL 15(NUMBER 4), 355
• LEACH, L, CLARK, P, LAMPUGNANI, M G, ARROYO, A G, DEJANA, E and FIRTH, J A, 1993. Immunoelectron characterisation of the inter-endothelial junctions of human term placenta. Journal of Cell Science. 104 ( Pt 4), 1073-81
• EATON, B M, LEACH, L and FIRTH, J A, 1993. Permeability of the fetal villous microvasculature in the isolated perfused term human placenta. Journal of Physiology. 463, 141-55
• LEACH, L and FIRTH, J A, 1992. Cell and Tissue Research. 268(3), 447-52
• LEACH, L, EATON, B M, FIRTH, J A and CONTRACTOR, S F, 1991. Histochemical Journal. 23(10), 444-9
• LEACH, L, EATON, B M, FIRTH, J A and CONTRACTOR, S F, 1990. Cell and Tissue Research. 261(2), 383-8
• LEACH, L, EATON, B M, FIRTH, J A and CONTRACTOR, S F, 1989. Cell and Tissue Research. 257(3), 603-7
• LEACH, L, TRUDGILL, D L and GAHAN, P B, 1987. Histochemical Journal. 19(9), 471-5
• LEACH, L, LAMMIMAN, M J, BABAWALE, M O, HOBSON, S A, BROMILOU, B, LOVAT, S and SIMMONDS, M J, Placenta.. 21(5-6), 547-57