Dr Gendie Lash
- Address: Reproductive and Vascular Biology Group
Institute of Cellular Medicine
Faculty of Medical Sciences
3rd Floor, William Leech Building
Newcastle upon Tyne
I obtained my BSc(Hons) and PhD in Biochemistry from The University of Otago, Dunedin, New Zealand. I then held Post-Doctoral research positions at University of Nottingham (Nottingham UK) and Queen's University (Kingston, Ontario, Canada) before coming to Newcastle University in 2002. I have worked in both Clinical and Basic Science departments and my research focus has always been on reproductive biology.
I am the Editor of Trophoblast Research (supplement to Placenta) and am on the Editorial Boards of Journal of Reproductive Immunology and Biology of Reproduction.
I am a member of several professional organisations: ESHRE, IFPA, SSR, SRF, ESRI, ISIR.
I have two main areas of research interest that focus on non-pregnant endometrium blood vessel development and early uterine adaptations to pregnancy.
Blood Vessel Development in Non-Pregnant Endometrium
Altered development of endometrial spiral arterioles has been associated with menorrhagia, recurrent implantation failure and recurrent miscarriage. In particular, vascular smooth muscle cell association with endothelial cells and differentiation appear to be affected. Menorrhagia, recurrent miscarriage and recurrent implantation failure significantly affect a woman’s reproductive health and quality of life. The endometrium is one of the few adult tissues that undergoes regular vascular development and therefore serves as an excellent model to study endothelial cell/vascular smooth muscle cell association and vascular smooth muscle cell differentiation. The wider applicability of my work in this area is evident by the funding I have received to investigate the role of breast cancer stem cells in vascular development (with Dr Annette Meeson, Newcastle University). I have developed two in vitro models to study vascular smooth muscle cell/endothelial cell association and vascular smooth muscle cell differentiation in relation to the endometrium. This work is coupled with immunohistochemical analysis of spiral arterioles and angiogenic growth factor expression in endometrium of women with menorrhagia or recurrent miscarriage. One of the models involves the use of cell lines to tease out the basic events required for vascular smooth muscle cell/endothelial cell association and vascular smooth muscle cell differentiation while the other uses cultured endometrial biopsies. Recent data from my laboratory has shown a dysregulation of calponin and smoothelin (vascular smooth muscle cell contractile proteins) in women with menorrhagia. These data have opened up a new area of study into regulation of vascular smooth muscle cell contractile proteins and the functional consequence of their dysregulation. I believe this is a key area of research that I can significantly contribute to using these novel approaches. Research collaborations have been established with Professor Siobhan Quenby (recurrent miscarriage, Warwick University), Dr Susan Laird (recurrent miscarriage, Sheffield Hallam University), Dr Annette Meeson (cancer stem cells and vascular development, Newcastle University), Professor Michael Taggart (vascular contractility, Newcastle University), Dr Jane Girling (endometrial blood vessel development, University of Melbourne, Australia) and Dr Dharani Hapangama (menorrhagia, University of Liverpool).
Uterine adaptation to pregnancy
During early human pregnancy placental extravillous trophoblast cells invade the maternal uterus and facilitate remodelling of the uterine spiral arteries. Failure of these processes is associated with several complications of pregnancy including pre-eclampsia, fetal growth restriction and miscarriage. The molecular triggers of these processes are little understood. Work in my laboratory focuses on the role of two uterine leucocyte populations, uterine natural killer cells and macrophages, in mediating these events. I have shown that uterine natural killer cells facilitate the early stages of spiral artery remodelling prior to extravillous trophoblast cell involvement primarily through secretion of proteases and angiopoietin 2. In addition, they stimulate extravillous trophoblast cell invasion via IL-8. My more recent work has concentrated on the fate of vascular smooth muscle cells during the remodelling process. I have shown that they migrate away from the vessel (although the cues for this are currently unknown, extravillous trophoblast cell derived factors are likely to play a role), undergo apoptosis and are phagocytosed by uterine macrophages. Full understanding of the spiral artery remodelling process and the molecular triggers involved, including their cellular source, is essential for developing therapeutics for various complications of pregnancy. My research is at the forefront of this understanding. Research collaborations have been established with Dr Judith Bulmer (uterine natural killer cells and placental bed histology, Newcastle University) and Professor Jan Ernerudh (reproductive immunology, Linkoping University, Sweden).
Wellbeing of Women
JGW Patterson Foundation
British Heart Foundation
I currently lecture on two MRes modules.
Cardiovascular Science in Health and Disease (Angiogenesis and vascular growth in health and disease II)
Stem Cells and Regenerative Medicine (Immunobiology of stem cells)
- Biswas Shivhare S, Bulmer JN, Innes BA, Hapangama DK, Lash GE. Altered vascular smooth muscle cell differentiation in the endometrial vasculature in menorrhagia. Human Reproduction 2014, 29(9), 1884-1894.
- O'Tierney-Ginn PF, Lash GE. Beyond pregnancy: modulation of trophoblast invasion and its consequences for fetal growth and long-term children's health. Journal of Reproductive Immunology 2014, 104-105, 37-42.
- Fox CE, Lash GE, Pretlove SJ, Chan BC, Holder R, Kilby MD. Maternal Plasma and Amniotic Fluid Cytokines in Monochorionic, Diamniotic Twin Pregnancies Complicated by Twin-to-Twin Transfusion Syndrome. Fetal Diagnosis and Therapy 2014, 35(4), 280-288.
- Vasilopoulou E, Loubiere LS, Lash GE, Ohizua O, McCabe CJ, Franklyn JA, Kilby MD, Chan SY. Triiodothyronine regulates angiogenic growth factor and cytokine secretion by isolated human decidual cells in a cell-type specific and gestational age-dependent manner. Human Reproduction 2014, 29(6), 1161-1172.
- Pitman H, Innes BA, Robson SC, Bulmer JN, Lash GE. Altered expression of interleukin-6, interleukin-8 and their receptors in decidua of women with sporadic miscarriage. Human Reproduction 2013, 28(8), 2075-2086.
- Vasilopoulou E, Loubiere LS, Heuer H, Trajkovic-Arsic M, Darras VM, Visser TJ, Lash GE, Whitley GS, McCabe CJ, Franklyn JA, Kilby MD, Chan SY. Monocarboxylate Transporter 8 Modulates the Viability and Invasive Capacity of Human Placental Cells and Fetoplacental Growth in Mice. PLoS ONE 2013, 8(6), e65402.
- Champion H, Innes BA, Robson SC, Lash GE, Bulmer JN. Effects of interleukin-6 on extravillous trophoblast invasion in early human pregnancy. Molecular Human Reproduction 2012, 18(8), 391-400.
- Hannon T, Innes BA, Lash GE, Bulmer JN, Robson SC. Effects of local decidua on trophoblast invasion and spiral artery remodeling in focal placenta creta - An immunohistochemical study. Placenta 2012, 33(12), 998-1004.
- Lash GE, Innes BA, Drury JA, Robson SC, Quenby S, Bulmer JN. Localization of angiogenic growth factors and their receptors in the human endometrium throughout the menstrual cycle and in recurrent miscarriage. Human Reproduction 2012, 27(1), 183-195.
- Bulmer JN, Innes BA, Levey J, Robson SC, Lash GE. The role of vascular smooth muscle cell apoptosis and migration during uterine spiral artery remodeling in normal human pregnancy. FASEB Journal 2012, 26(7), 2975-2985.
- Robson A, Harris LK, Innes BA, Lash GE, Aljunaidy MM, Aplin JD, Baker PN, Robson SC, Bulmer JN. Uterine natural killer cells initiate spiral artery remodeling in human pregnancy. FASEB Journal 2012, 26(12), 4876-4885.
- Lash GE, Bulmer JN. Do uterine natural killer (uNK) cells contribute to female reproductive disorders?. Journal of Reproductive Immunology 2011, 88(2), 156-164.
- Lash GE, Naruse K, Robson A, Innes BA, Searle RF, Robson SC, Bulmer JN. Interaction between uterine natural killer cells and extravillous trophoblast cells: effect on cytokine and angiogenic growth factor production. Human Reproduction 2011, 26(9), 2289-2295.
- Otun HA, Lash GE, Innes BA, Bulmer JN, Naruse K, Hannon T, Searle RF, Robson SC. Effect of tumour necrosis factor-alpha in combination with interferon-gamma on first trimester extravillous trophoblast invasion. Journal of Reproductive Immunology 2011, 88(1), 1-11.
- Bulmer JN, Williams PJ, Lash GE. Immune cells in the placental bed. International Journal of Developmental Biology 2010, 54(2-3), 281-294.
- Volchek M, Girling JE, Lash GE, Cann L, Kumar B, Robson SC, Bulmer JN, Rogers PAW. Lymphatics in the human endometrium disappear during decidualization. Human Reproduction 2010, 25(10), 2455-2464.
- Fox CE, Lash GE, Pretlove SJ, Chan BC, Holder R, Kilby MD. Maternal plasma and amniotic fluid angiogenic factors and their receptors in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome. Ultrasound in Obstetrics and Gynecology 2010, 35(6), 695-701.
- Lash GE, Pinto LA. Multiplex cytokine analysis technologies. Expert Review of Vaccines 2010, 9(10), 1231-1237.
- Lash GE, Otun HA, Innes BA, Percival K, Searle RF, Robson SC, Bulmer JN. Regulation of extravillous trophoblast invasion by uterine natural killer cells is dependent on gestational age. Human Reproduction 2010, 25(5), 1137-1145.
- Lash G, Robson S, Bulmer J. Review: Functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta 2010, 31(Supplement A), S87-S92.
- De Oliveira LG, Lash GE, Murray-Dunning C, Bulmer JN, Innes BA, Searle RF, Sass N, Robson SC. Role of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion. Placenta 2010, 31(7), 595-601.
- Lash GE, Naruse K, Innes BA, Robson SC, Searle RF, Bulmer JN. Secretion of Angiogenic Growth Factors by Villous Cytotrophoblast and Extravillous Trophoblast in Early Human Pregnancy. Placenta 2010, 31(6), 545-548.
- Naruse K, Innes BA, Bulmer JN, Robson SC, Searle RF, Lash GE. Secretion of cytokines by villous cytotrophoblast and extravillous trophoblast in the first trimester of human pregnancy. Journal of Reproductive Immunology 2010, 86(2), 148-150.
- Schiessl B, Innes BA, Bulmer JN, Otun HA, Chadwick TJ, Robson SC, Lash GE. Localization of Angiogenic Growth Factors and Their Receptors in the Human Placental Bed Throughout Normal Human Pregnancy. Placenta 2009, 30(1), 79-87.
- Naruse K, Lash GE, Innes BA, Otun HA, Searle RF, Robson SC, Bulmer JN. Localization of matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitors for MMPs (TIMPs) in uterine natural killer cells in early human pregnancy. Human Reproduction 2009, 24(3), 553-561.
- Naruse K, Lash GE, Bulmer JN, Innes BA, Otun HA, Searle RF, Robson SC. The Urokinase Plasminogen Activator (uPA) System in Uterine Natural Killer Cells in the Placental Bed During Early Pregnancy. Placenta 2009, 30(5), 398-404.
- Quenby S, Nik H, Innes B, Lash G, Turner M, Drury J, Bulmer J. Uterine natural killer cells and angiogenesis in recurrent reproductive failure. Human Reproduction 2009, 24(1), 45-54.
- Lash GE, Hornbuckle J, Brunt A, Kirkley M, Searle RF, Robson SC, Bulmer JN. Effect of Low Oxygen Concentrations on Trophoblast-Like Cell Line Invasion. Placenta 2007, 28(5-6), 390-398.
- Maruthachalam, K., Lash, G.E., Shenton, B.K., Horgan, A. Tumour cell dissemination following endoscopic stent insertion. British Journal of Surgery 2007, 94(9), 1151-1154.
- Lash GE, Scaife PJ, Innes BA, Otun HA, Robson SC, Searle RF, Bulmer JN. Comparison of three multiplex cytokine analysis systems: Luminex, SearchLight™ and FAST Quant®. Journal of Immunological Methods 2006, 309(1-2), 205-208.
- Lash GE, Schiessl B, Kirkley M, Innes BA, Cooper A, Searle RF, Robson SC, Bulmer JN. Expression of angiogenic growth factors by uterine natural killer cells during early pregnancy. Journal of Leukocyte Biology 2006, 80(3), 572-580.
- Lash GE, Otun HA, Innes BA, Kirkley M, De Oliveira L, Searle RF, Robson SC, Bulmer JN. Interferon-γ inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels. The FASEB Journal 2006, 20(14), 2512-2518.
- Lash GE, Otun HA, Innes BA, Bulmer JN, Searle RF, Robson SC. Low oxygen concentrations inhibit trophoblast cell invasion from early gestation placental explants via alterations in levels of the urokinase plasminogen activator system. Biology of Reproduction 2006, 74(2), 403-409.
- Lash GE, Otun HA, Innes BA, Bulmer JN, Searle RF, Robson SC. Inhibition of trophoblast cell invasion by TGFB1, 2, and 3 is associated with a decrease in active proteases. Biology of Reproduction 2005, 73(2), 374-381.
- Lash GE, Bulmer JN, Innes BA, Drury JA, Robson SC, Quenby S. Prednisolone treatment reduces endometrial spiral artery development in women with recurrent miscarriage. Angiogenesis 2011, 14(4), 523-532.
- Manning R, James C, Smith M, Innes B, Stamp E, Peebles D, Bulmer J, Robson S, Lash G. Are cervical cytokines, antimicrobials and microflora associated with pre-term birth in high-risk women?. In: RCOG World Congress. 2016, Birmingham, UK: Wiley-Blackwell Publishing Ltd.
- James CP, Peebles DM, Bajaj-Elliott M, Klein N, Manning R, Robson SC, Lash G. Bacteria Associated with Chorioamnionitis Are Present in the Cervix of Women Who Deliver Preterm and Are Associated with Increased Cervicovaginal HBD1 Expression. In: 63rd Annual Scientific Meeting. 2016, Montreal, Canada: Sage Publications, Inc.
- Lash GE, Pitman H, Morgan HL, Innes BA, Agwu CN, Bulmer JN. Decidual macrophages: key regulators of vascular remodeling in human pregnancy. Journal of Leukocyte Biology 2016, 100(2), 315-325.
- Lash GE, Bulmer JN, Li TC, Innes BA, Mariee N, Patel G, Sanderson J, Quenby S, Laird SM. Standardisation of uterine natural killer (uNK) cell measurements in the endometrium of women with recurrent reproductive failure. Journal of Reproductive Immunology 2016, 116, 50-59.
- Lash GE, Ernerudh J. Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage. Journal of Reproductive Immunology 2015, 108, 83-89.
- Lash GE, Delamare M, Haunch-Smith CM, Arvelund JS, Jenmalm MC, Mehta RB, Ernerudh J, Laird SM. Differential numbers of CD3 T lymphocytes in decidual basalis and decidua parietalis correlate with chemokine levels. In: The 12th Conference of the European Society for Reproductive Immunology. 2015, Oxford, UK: Elsevier Ireland Ltd.
- Lash GE. Editorial. Placenta 2015, 36, S1-S1.
- Lantang AM, Innes BA, Gan EH, Pearce SH, Lash GE. Expression of melanocortin receptors in human endometrium. Human Reproduction 2015, 30(10), 2404-2410.
- Barbaux S, Erwich JJHM, Favaron PO, Gil S, Gallot D, Golos TG, Gonzalez-Bulnes A, Guibourdenche J, Heazell AEP, Jansson T, Laprevote O, Lewis RM, Miller RK, Monk D, Novakovic B, Oudejans C, Parast M, Peugnet P, Pfarrer C, Pinar H, Roberts CT, Robinson W, Saffery R, Salomon C, Sexton A, Staff AC, Suter M, Tarrade A, Wallace J, Vaillancourt C, Vaiman D, Worton SA, Lash GE. IFPA meeting 2014 workshop report: Animal models to study pregnancy pathologies; new approaches to study human placental exposure to xenobiotics; biomarkers of pregnancy pathologies; placental genetics and epigenetics; the placenta and stillbirth and fetal growth restriction. Placenta 2015, 36(Suppl. 1), S5-S10.
- Lindau R, Svensson-Arvelund J, Mehta RB, Eklund D, Lash GE, Jenmalm MC, Ernerudh J. IL-34 at the human fetal maternal interface. In: European Society for Reproductive Immunology Annual Meeting. 2015, Oxford, UK: Elsevier Ireland Ltd.
- Shivhare SB, Bulmer JN, Lash GE. Immunity at the Maternal–Fetal Interface. In: Mestecky J, Strober W, Russell MW, Kelsall BL, Cheroutre H, Lambrecht BN, ed. Mucosal Immunology. Academic Press, 2015, pp.2231-2250.
- Shivhare SB, Bulmer JN, Innes BA, Hapangama DK, Lash GE. Menstrual cycle distribution of uterine natural killer cells is altered in heavy menstrual bleeding. Journal of Reproductive Immunology 2015, 112, 88-94.
- Lash GE. Molecular Cross-Talk at the Feto-Maternal Interface. Cold Spring Harbor Perspectives in Medicine 2015, 5(12), 1-15.
- Svensson-Arvelund J, Mehta RB, Lindau R, Mirrasekhian E, Rodriguez-Martinez H, Berg G, Lash GE, Jenmalm MC, Ernerudh J. The Human Fetal Placenta Promotes Tolerance against the Semiallogeneic Fetus by Inducing Regulatory T Cells and Homeostatic M2 Macrophages. Journal of Immunology 2015, 194(4), 1534-1544.
- Bulmer JN, Lash GE. The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders. In: Male Role in Pregnancy Loss and Embryo. Springer, 2015, pp.95-126.
- Lash GE, Bulmer JN. Trophoblast - Uterine Natural Killer Cell Interactions and Their Effect on Cytokines and Angiogenic Growth Factors. In: Duttaroy AK, Basak S, ed. Human Placental Trophoblasts: Impacts on Maternal Nutrition. CRC Press, 2015. In Press.
- Shivhare SB, Bulmer JN, Innes BA, Hapangama DK, Lash GE. Menstrual cycle distribution of uterine natural killer cells is altered in menorrhagia. In: International Federation of Fertility Societies 21st World Congress on Fertility and Sterility and the 69th Annual Meeting of the American Society for Reproductive Medicine. 2013, Boston, MA, USA: Elsevier.