Department: Comparative Biomedical Sciences

Campus: Hawkshead

Research Groups: Immune Regulation and Cancer

Mandi is a Reader in Reproductive Immunology. Mandi's research group that spans clinical and basic science research focuses on the immunobiology of the maternal-fetal interface, with a particular interest in pregnancy-related conditions in the mare in both normal pregnancy and those pregnancies that fail. She teaches graduate, undergraduate veterinary and bioveterinary students in reproductive anatomy and physiology and equine stud medicine. Along with Jackie Cardwell, and other RVC staff, supported by Prof Rick DeBowes (Washington State University) she has co-led the development and delivery of the 'Veterinary Team: Leadership & Development' programme and the RVC 'Professional Orientation & Development' (POD) programme - experiential learning programmes using an emotional intelligence framework for training in leadership skills and 'non-technical' clinical skills.

Mandi graduated from the University of Sydney in 1998 with a First Class Bachelor of Veterinary Science. Her interest in research begun as a veterinary student during which time she spent two summers in the U.S.A in the laboratories of Professor Douglas Antczak (Cornell University) and Dr. Craig Altier (North Carolina State University) working on projects in the fields of equine genomics and reproduction. Following graduation, she worked as a veterinarian in equine specialist practice in Scone, Australia and Newmarket, United Kingdom furthering her interest in equine  reproduction and neonatology.

In 2001, Mandi started a PhD in Biomedical Sciences at the John Curtin School of Medical Research (JCSMR Website), Australian National University, whilst continuing work part-time as an equine veterinarian. In 2005, she was the recipient of the 2006 Frank Fenner Medal and Dewar Milne Prize in Immunology awarded by the JCSMR for her PhD work. In 2005, Mandi returned to Cornell as a Post-doctoral research associate in the laboratory of Professor Douglas Antczak working on differentiation of placental trophoblast cells and regulation of immunity during pregnancy in the horse. Mandi joined the Royal Veterinary College as a Lecturer in the Department of Comparative Biomedical Sciences in 2007. Her current research interests combine her clinical training in reproduction and neonatology with her scientific background in the field of placental function and immunology. Her research is currently funded by HBLB, Thoroughbred Breeders Association, and Alborada Trust. In 2015 she was the recipeint of the Society of Reprouction and Fertility New Investigator Award for her research achievements. She currently is an Associate Editor for Frontiers in Reproduction and a member of the International Symposium of Equine Reproduction Committee (2016-2024) and on Council for the Society for Reproduction and Fertility (2018-present). 

The overall goal of Mandi's research program is to identify key mechanisms that permit normal growth and survival of the fetus and pathologies that interfer with this process. Her current research focuses on two aspects of pregnancy: (i) the mechanisms that regulate the development of the placenta in normal healthy pregnancies, (ii) identification and characterisation of causes of pregnancy failure. Her studies, which are primarily in the horse, address fundamental questions that aim to result in the development of novel therapies to treat and clincially manage conditions of equine pregnancy and infertility (e.g. abortion). One of the hormones of pregnancy her group studies, Chorionic gonadotropin, is produced by the placenta of both horses and humans during pregnancy, but not by most other species used experimentally. This means that results gained from their studies in the horse may also be valuable beyond equine health to provide new knowledge relevant and applicable to human reproduction.  

Currently Mandi's funded research projects fall into these areas; i) Genetics of early pregnancy loss in Thoroughbreds (funded by Thoroughbred Breeders Association), (ii) Unravelling genetic and environmental contributions to abortions associated with umbilical pathologies (funded by Alborada Trust), (iii) Development of software for managing breeding mares (Concept Development Fund, RVC), (iv) collaboration with Professor Kristien Verheyen, Does early life experience affect injury risk and performance in later life (HBLB), (v) collaboration with Dr Suzannah Williams and Lindsay Baxter, University of Oxford, Age-related changes in oocyte quality and implications for early pregnancy failure using a horse model (Wellcome TRust Clinician PhD studentship to Dr Lindsay Baxter). 

AM de Mestre, BV Rose, YM Chang, DC Wathes, KLP Verheyen. Multivariable analysis to determine risk factors associated with early pregnancy loss in thoroughbred broodmares, Theriogenology, 2018, in press

Read JE, Cabrera-Sharp V, Offord V, Mirczuk SM, Allen SP, Fowkes RC, de Mestre AM. Dynamic changes in gene expression and signalling during trophoblast development in the horse. Reproduction. 2018 Jul 10. pii: REP-18-0270. doi: 10.1530/REP-18-0270

Jordan E Read, Victoria Cabrera-Sharp, Phoebe Kitscha, Judith E Cartwright, Peter J King, Rob C Fowkes and Amanda M de Mestre. Glial Cells Missing 1 regulates equine Chorionic Gonadotrophin beta subunit via binding to the proximal promoter. Front. Endocrinology, 26 April 2018, 9: 195 https://doi.org/10.3389/fendo.2018.00195

Timpson, A; de Mestre, AM; Elliott, J; Harris, PA; Cheng, Z; Mirczuk, S M; Callan, L; Rainbow, L; Menzies-Gow, NJ.
Seasonal and dietary influences on adipose tissue and systemic gene expression in control and previously laminitic ponies.
Journal of Equine Veterinary Science, 2018, in press

ROSE BV, FIRTH M, MORRIS B, ROACH JM, WATHES DC, VERHEYEN KLP, DE MESTRE AM.Descriptive study of current therapeutic practices, clinical reproductive findings and incidence of pregnancy loss in intensively managed thoroughbred mares. Anim Reprod Sci. 2018 Jan;188:74-84. doi: 10.1016/j.anireprosci.2017.11.011.

CAMPBELL MLH, HAMPSHIRE D, HAMSTEAD L, ROSE B, SMITH KC, DE MESTRE AM The effects of intrauterine infusion of peanut oil on endometrial health, salivary cortisol and interovulatory period in mares. Theriogenology, 2017 Oct 15;102:116-125. doi: 10.1016/j.theriogenology.2017.07.009. Epub 2017 Jul 13.

ALEKSIC D, BLASCHKE L, MIßBACH S, HÄNSKE J, WEIß W, HANDLER J, ZIMMERMANN W, CABRERA-SHARP V, READ JE, DE MESTRE AM, O'RIORDAN R, MOORE T, KAMMERER R. Convergent evolution of pregnancy-specific glycoproteins in the human and horse. Reproduction. 2016 Jun 8.

CARNEY K, CHANG YM, WILSON S, CALNAN C, REDDY PS, CHAN WY, GILMARTIN T, HERNANDEZ G, SCHAFFER L, HEAD SR, MORLEY J, DE MESTRE AM, AFFLECK K, GARDEN OA. Regulatory T-cell-intrinsic amphiregulin is dispensable for suppressive function. J Allergy Clin Immunol. 2016 Jun;137(6):1907-9.

B.V. ROSE, V. CABRERA-SHARP, M.J. FIRTH, F.E. BARRELET, S. BATE, I.J. CAMERON, J.R. CRABTREE, J. CROWHURST, A.J. MCGLADDERY, H. NEAL, J. PYNN, O.D. PYNN, C. SMITH, Z. WISE, K.L.P. VERHEYEN, D.C. WATHES, A.M. DE MESTRE A method for isolating and culturing placental cells from failed early equine pregnancies. Placenta, Volume 38, February 2016, Pages 107–111

CABRERA-SHARP V, READ JE, RICHARDSON S, KOWALSKI AA, ANTCZAK DF, CARTWRIGHT JE, MUKHERJEE A, DE MESTRE AM. SMAD1/5 signaling in the early equine placenta regulates trophoblast differentiation and chorionic gonadotropin secretion. Endocrinology. 2014 Aug;155(8):3054-64

ROSE, B., FIRTH, M., MORRIS, B., NICHOLSON, C., VERHEYEN, K., WATHES, D.C. AND DE MESTRE, A.M. (2014), Incidence and Risk Factors Associated with Early Pregnancy Loss in Thoroughbreds. Equine Veterinary Journal, 46: 16. doi: 10.1111/evj.12323_35

ACKERMAN WE 4TH, CARTER AM, DE MESTRE AM, GOLOS TG, JESCHKE U, KUSAKABE K, LAURENT LC, PARAST MM, ROBERTS RM, ROBINSON JM, RUTHERFORD J, SOMA H, TAKIZAWA T, UI-TEI K, LASH GE. IFPA Meeting 2012 Workshop Report I: comparative placentation and animal models, advanced techniques in placental histopathology, human pluripotent stem cells as a model for trophoblast differentiation. Placenta. 2013 Mar;34 Suppl:S3-5

ANTCZAK, DF, DE MESTRE, AM, WILSHER S AND ALLEN WR. The Equine Endometrial Cup Reaction: A Feto-maternal Signal of Significance. Annual Review of Animal Biosciences, 2013, Vol. 1419

DE MESTRE A. Reproductive failure in horses: identifying the problem. Vet Rec. 2013 Jan 12;172(2):42

NORONHA, L. E., HUGGLER, K. E., DE MESTRE, A. M., MILLER, D. C. AND ANTCZAK, D. F. (2012). Molecular evidence for natural killer-like cells in equine endometrial cups. Placenta. 33(5):379-86. PubMed ID 22357194

CRABTREE, J.R., CHANG, Y., AND, DE MESTRE A.M. (2012). Clinical presentation, treatment and possible causes of persistent endometrial cups illustrated by two cases. Equine Veterinary Education. 24(5):251-259.

ACKERMAN WE 4TH, BULMER JN, CARTER AM, CHAILLET JR, CHAMLEY L, CHEN CP, CHUONG EB, COLEMAN SJ, COLLET GP, CROY BA, DE MESTRE AM, DICKINSON H, DUCRAY J, ENDERS AC, FOGARTY NM, GAUSTER M, GOLOS T, HAIDER S, HEAZELL AE, HOLLAND OJ, HUPPERTZ B, HUSEBEKK A, JOHN RM, JOHNSEN GM, JONES CJ, KALIONIS B, KÖNIG J, LORENZON AR, MOFFETT A, MOREIRA DE MELLO JC, NUZZO AM, PARHAM P, PAROLINI O, PETROFF MG, PIDOUX G, RAMÍREZ-PINILLA MP, ROBINSON WP, ROLFO A, SADOVSKY Y, SOMA H, SOUTHCOMBE JH, TILBURGS T, LASH GE. (2012). IFPA Meeting 2011 workshop report III: Placental immunology; epigenetic and microRNA-dependent gene regulation; comparative placentation; trophoblast differentiation; stem cells. Placenta. 33 Suppl:S15-22. PubMed ID 22154501

DE MESTRE A.M., HANLON D., ADAMS, A.P., RUNCAN E., LEADBEATER J.C., ERB H., COSTA C., MILLER D., ALLEN W.R., ANTCZAK,D.F. (2011). Functions Of Ectopically Transplanted Invasive Horse Trophoblast. Reproduction. 141(6):849-56. Faculty of 1000 selection PubMed ID 21389079

ROBBIN M.G., WAGNER B., NORONHA L.E., ANTCZAK D.F. AND DE MESTRE A.M. (2011). Subpopulations of equine blood lymphocyte expressing regulatory T cell markers. Vet Immunol Immunopathol 140:90-101 PubMed ID 21208665

DE MESTRE AM., ANTCZAK, DF., AND ALLEN, WR. (2010). 'Equine Chorionic Gonadotropin' in Equine Reproduction, 2nd edition, A. McKinnon, E Squires, W. Vaala, D. Varner, Blackwell Publishing

DE MESTRE, A.M., NORONHA, L.E., WAGNER, B., AND ANTCZAK, D.F. (2010). Split immunological tolerance to trophoblast. Int. J. Dev. Biol. 54(2-3):445-55. PubMed ID 19876828

DE MESTRE, A.M., MILLER, D., ROBERSON, MS., LIFORD, J., CHIZMAR, LC., MCLAUGHLIN, K.E., AND ANTCZAK, D. F. (2009). Glial cells missing homologue 1 is induced in differentiating equine chorionic girdle trophoblast cells. Biol. Reprod. 80:227-234. PubMed ID 18971425

DE MESTRE, A.M., BACON, S.J., COSTA, C.C., LEADBEATER, J.C., NORONHA, L.E., STEWART, F., AND ANTCZAK, D.F. (2008). Modeling trophoblast differentiation using equine chorionic girdle vesicles. Placenta 29:158-169. Pubmed ID 18054076

DE MESTRE, A.M., STAYKOVA, M.A., HORNBY, J.R., WILLENBORG, D.O., AND HULETT, M.D. (2007). Expression of the heparan sulfate-degrading enzyme heparanase is induced in infiltrating CD4+ T cells in experimental autoimmune encephalomyelitis and regulated at the level of transcription by early growth response gene 1. J. Leukoc. Biol. 82:1289-1300. Pubmed ID 17656651

DE MESTRE, A.M., SOE-HTWE, T., SUTCLIFFE, E.L., RAO, S., PAGLER, E.B., HORNBY, J.R., AND HULETT, M.D. (2007). Regulation of mouse heparanase gene expression in T lymphocytes and tumor cells. Immunol. Cell Biol. 85:205-214. Pubmed ID 17213834

DE MESTRE, A.M., RAO, S., HORNBY, J.R., SOE-HTWE, T., KHACHIGIAN, L.M., AND HULETT, M.D. (2005). Early growth response gene 1 (EGR1) regulates heparanase gene transcription in tumor cells. J. Biol. Chem. 280:35136-35147. PubMed ID 16093249

DE MESTRE, A.M., KHACHIGIAN, L.M., SANTIAGO, F.S., STAVKOVA, M.A., AND HULETT, M.D. (2003). Regulation of inducible heparanase gene transcription in activated T cells by early growth response 1. J. Biol. Chem. 278:50377-50385. PubMed ID 14522979

MURPHIE*, A.M., HOPMAN, T.J., SCHUG, M.D., AQUADRO, C.F., BOWLING, A.T., MURRAY, J.D., CAETANO, A.R. AND ANTCZAK, D.F. (1999). Equine dinucleotide repeat loci COR021-COR040. Anim. Genet. 30:235-237. Pubmed ID 10443004

 

Conference papers 2015-2018

de Mestre AM, BV Rose, YM Chang, DC Wathes, KLP Verheyen. Factors that modify the risk of early pregnancy loss and early conceptus growth in Thoroughbreds, International Symposium in Equine Reproduction, Cambridge UK, July 2018.

de Mestre AM. Update on pregnancy loss. ISER Veterinary and Breeders Symposium, Newmarket, July 2018. 

de Mestre, AM Update on risk factors for pregnancy loss and how to ameliorate them. BEVA Congress, September 2017,

de Mestre, AM Current broodmare management in the UK: could it be done better? BEVA Congress, September 2017

de Meste AM, ‘Early pregnancy loss – current research and the state of our knowledge’ and ‘Immunology of pregnancy and ‘Immunological aspects of early pregnancy loss’ Rossdales Pregnant Mare and Stallion Course, January 2017, Newmarket. 

JE Read, V Cabrera-Sharp, V Offord, S Mirczuk, R Fowkes, AM de Mestre. Dynamic changes in gene expression and signalling during early placental development in the horse. Fertility, Edinburgh, UK, January 2017. 

de Mestre AM, Molecular Mechanisms Regulating Early Placental Development in the Horse. Society for the Study of Reproduction, July 2016, San Diego, USA. 

de Mestre AM Molecular mechanisms regulating early equine placental development in health and disease. Society for Reproduction and Fertility, Oxford, UK. July 2015

de Meste AM . Transcriptional regulation of equine Chorionic Gonadotrophin. International Conference on Biotechnology and Welfare in Animal Husbandry Krakow, Poland, June 2015. 

de Meste AM Risk Factors associated with early pregnancy failure. British Society for Animal Science Science with Impact Annual Meeting, Chester, UK, April 2015. 

 

Mandi teaches reproductive biology on the following courses; Bvetmed1, Bvetmed2, GAB, Bvetmed5 (Module leader for equine stud medicine), and BSc3. She also supervises 4-6 undergraduate students each year on the BSc Bioveterinary Science and BVetMed course who choose to carry out projects in her laboratory either as part of the course or over the summer. Mandi has a strong interest in mentoring veterinary students in research. She was Course Director for Veterinary Team Leadership and Professionalism (VTLP) course for veterinary, nursing and bioveterinary science undergraduate students that aims to develop students leadership and teamwork skills through self awareness, social awareness and relational competence. She is Co-Leader of the Professional Orientation and Development Programme for BVM3 students. 

Mandi and her group regularly present to industry representatives, horse breeders and veterinary surgeons. Recently this has included presentations at Thoroughbred Breeders Association Breeders Day and  Horsetech 2017 and 2018.  Please get in touch if your organisation would like us to speak to your members about updates in equine reproduction.

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