Faculty of Medical Sciences

Staff Profile

Dr Gendie Lash

Background

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. 

Research

Research themes

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). 

 

Research funding

Wellbeing of Women

JGW Patterson Foundation

British Heart Foundation 

Teaching

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)

  

Publications