Associate Professor Wendy Ingman
THRF A/Prof of Breast Cancer Research/National Breast Cancer Foundation Early Career Fellow
Head of the Breast Biology and Cancer Unit
A/Prof Wendy Ingman graduated from a PhD at the University of Adelaide in 2002 and conducted postdoctoral training as an NHMRC CJ Martin Fellow at the Albert Einstein College of Medicine, NY, returning to Adelaide in 2005. Wendy made the transition to independent researcher in 2009 with an NHMRC New Investigator Project grant. In 2011 she was appointed an NBCF Early Career Fellow and THRF A/Prof of Breast Cancer Research, and established a laboratory at TQEH which is her current appointment. The Unit employs a variety of techniques including 3 dimensional culture of human breast tissue and genetically modified mouse models to investigate breast biology and how disease states of the breast occur.
The Breast Biology and Cancer Unit is located at the Basil Hetzel Institute within The Queen Elizabeth Hospital, and at the Medical School on Frome Rd at the main University campus.
The breast is a unique organ, because it goes through the majority of its development a long time after birth. The major phases of breast development occur during puberty, where the cellular structures develop to maturity, and pregnancy where the cells become altered, so as to enable milk production during lactation. Milk is an essential part of the life cycle of all mammals. In fact, provision of milk to newborns from the breast (also known as the mammary gland) is one of the defining features of mammals. Therefore, it is critically important to the survival of mammalian species that mammary gland function is protected, so that milk can be produced to nurture the next generation. However, the extensive changes that occur in the breast pose some unique immunological challenges. The immune system is programmed to maintain the status quo by mounting attacks against invading bacteria and viruses, and preventing rogue cells from developing into tumours. So when a tissue undergoes such extensive changes as the breast does, the immune system must develop particular strategies to allow this to happen. Our research investigates the immunology of the breast and how immune system cells affect cancer risk and development of mastitis.
Immune cells in breast development and cancer susceptiblity
Breast cancer is the most common type of cancer in Australian women, affecting 1 in 8 before the age of 85. It is more common than skin melanoma and lung cancer. The skin and lungs are two tissues that are frequently bombarded with cancer-initiating factors, such as UV rays from the sun and smoke and pollutants in the air we breathe. Why then, does the breast so commonly get cancer when it is not a tissue that is particularly exposed to the environmental agents that increase cancer risk in other major organs? It would follow that there must be something unique about this tissue that makes it particularly susceptible.
The body has a number of systems in place to help repair DNA mutations when they occur, thus protecting the body from cancer. Cells of the immune system are part of the body’s defence against cancer, and can recognise and eliminate cells containing DNA mutations. However, our research shows that in the breast, immune cells called macrophages are also critical for the normal function across the ovarian cycle. The requirement for macrophages for the everyday functioning of this tissue is unique to the breast, and this can affect how the immune system responds to DNA mutations. The overarching objective of this research is to provide therapies that promote better immune function in the breast, thus reducing a woman’s lifetime risk of developing the disease. Follow this link for a recent media story.
Lactation mastitis is a debilitating inflammatory disease that affects 1 in 4 breastfeeding women. The disease causes localised pain, and is frequently accompanied by the rapid onset of systemic symptoms including fever, muscle aches, chills and fatigue. Sometimes mastitis leads to a breast abscess, which must be surgically drained, and in severe disease there can be permanent disfiguration of the breast. Low milk supply frequently accompanies these symptoms and combined, the challenges posed by this disease lead many women to cease breastfeeding.
Although bacteria are associated with lactation mastitis, there remains speculation on how significant bacterial load is in development of the disease. Little is known of the significance of the host innate inflammatory response in determining the severity of mastitis and disease resolution. We are investigating the role of innate immune sensors in development and resolution of mastitis using mouse models. Our studies may offer new pharmacological interventions for mastitis that could be used alone, or in combination with currently employed treatments. For current technology applications see here.
Ingman WV, Glynn DJ, Hutchinson MR. Mouse models of mastitis - how physiological are they? International Breastfeeding Journal in press
Boyle ST, Ingman WV, Poltavets V, Faulkner JW, Whitfield RJ, McColl SR, Kochetkova M. The chemokine receptor CCR7 promotes mammary tumorigenesis through amplification of stem-like cells. Oncogene 2015 ePub 16/3/15
Dasari P, Sharkey DJ, Noordin E, Glynn DJ, Hodson LJ, Chin PY, Evdokiou A, Robertson SA, Ingman WV. Hormonal regulation of the cytokine microenvironment in the mammary gland. Journal of Reproductive Immunology 2014 106:58-66
Zinonos I, Luo KW, Labrinidis A, Liapis V, Hay S, Panagopoulos B, DeNichilo M, Ko CH, Yue GG, Bik-San Lau C, Ingman W, Ponomarev V, Atkins GJ, Findlay DM, Zannettino ACW, Evdokiou A. Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma. Cancer Letters 2015 357(1):160-169
Care AS, Ingman WV, Moldenhauer LM, Jasper MJ, Robertson SA. Ovarian steroid hormone-regulated uterine remodelling occurs independently of macrophages in mice. Biology of Reproduction 2014 91(3):60-72
Sun X, Ingman WV. Cytokine networks that mediate epithelial cell-macrophage crosstalk in the mammary gland: implications for development and cancer. Journal of Mammary Gland Biology and Neoplasia 2014 19:191-201
Ingman WV, Glynn DJ, Hutchinson MR. Inflammatory mediators in mastitis and lactation insufficiency. Journal of Mammary Gland Biology and Neoplasia 2014 19:161-167
Zinonos I, Labrinidis A, Liapis V, Hay S, Panagopoulos V, Denichilo M, Ponomarev V, Ingman W, Atkins GJ, Findlay DM, Zannettino AC, Evdokiou A. Doxorubicin overcomes resistance to drozitumab by antagonizing Inhibitor of Apoptosis Proteins (IAPs). Anticancer Research 2014 34(12):7007-20
Need EF, Atashgaran V, Ingman WV, Dasari P. Hormonal regulation of the immune microenvironment in the mammary gland. Journal of Mammary Gland Biology and Neoplasia 2014 19:229-239
Zinonos I, Lou KW, Labrinidis A, Liapis V, Hay S, Panagopoulos V, DeNichilo M, Ponomarev V, Ingman W, Atkins GJ, Findlay DM, Zannettino ACW, Evdokiou A. Pharmacologic inhibition of bone resorption prevents cancer-induced osteolysis but enhances soft tissue metastasis in a mouse model of osteolytic breast cancer. International Journal of Oncology 2014 45(2):532-40
Glynn DJ, Hutchinson MR, Ingman WV. Toll-like receptor 4 regulates lipopolysaccharide-induced inflammation and lactation insufficiency in a mouse model of mastitis. Biology of Reproduction 2014 90(5):91
Huo CW, Chew GL, Britt KL, Ingman WV, Henderson MA, Hopper JL, Thompson EW. Mammographic density-a review on the current understanding of its association with breast cancer. Breast Cancer Research and Treatment 2014 144(3):479-502
Hodson LJ, Chua ACL, Evdokiou A, Robertson SA, Ingman WV. Macrophage phenotype in the mammary gland fluctuates over the course of the estrous cycle and is regulated by ovarian steroid hormones. Biology of Reproduction 2013 89(3):65
Sun X, Robertson SA, Ingman WV. Regulation of epithelial cell turnover and macrophage phenotype by epithelial cell-derived transforming growth factor beta1 in the mammary gland. Cytokine 2013 61(2):377-88.
Care AS, Diener KR, Jasper MJ, Brown HM, Ingman WV, Robertson SA. Macrophages regulate corpus luteum development during embryo implantation in mice. Journal of Clinical Investigation 2013 123(8):3472-87.
Hull ML, Johan MZ, Hodge WL, Robertson SA, Ingman WV. Host-derived TGFB1 deficiency suppresses lesion development in a mouse model of endometriosis. American Journal of Pathology 2012 180(3): 880-887
Ricciardelli C, Frewin KM, Tan IA, Williams ED, Opeskin K, Pritchard MA, Ingman WV, Russell DL. The Adamts1 protease gene is required for mammary tumor growth and metastasis. American Journal of Pathology 2011 179(6):3075-3085
Peters AA, Ingman WV, Tilley WD, Butler LM. Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and post-pubertal murine mammary gland. Endocrinology 2011 152(10):3728-3737
Jasper MJ, Care AS, Sullivan B, Ingman WV, Aplin JD, Robertson SA. Macrophage-derived LIF and IL1B regulate α(1,2)fucosyltransferase 2 (Fut2) expression in mouse uterine epithelial cells during early pregnancy. Biology of Reproduction 2011 84(1):179-188
Chua ACL, Hodson LJ, Moldenhauer LM, Robertson SA, Ingman WV. Dual roles for macrophages in ovarian cycle-associated development and remodelling of the mammary gland epithelium. Development 2010 137:4229-4238
Ingman WV, McGrath LM, Breed WG, Musgrave IF, Robker RL, Robertson SA. The mechanistic basis for sexual dysfunction in male transforming growth factor beta1 null mutant mice. Journal of Andrology 2010 31(2):95-107
Ingman WV, Robertson SA. The essential roles of TGFB1 in reproduction. Cytokine and Growth Factor Reviews 2009 20(3):233-239
McGrath LM, Ingman WV, Robker RL, Robertson SA. Exogenous transforming growth factor beta1 replacement and fertility in male Tgfb1 null mutant mice. Reproduction, Fertility and Development 2009 21(4):561-570
Ingman WV, Robertson SA. Mammary gland development in transforming growth factor beta1 null mutant mice: systemic and epithelial effects. Biology of Reproduction 2008 79:711-717
Ingman WV, Jones RL. Cytokine knockouts in reproduction: The use of gene ablation to dissect the roles of cytokines in reproductive biology. Human Reproduction Update 2008 14:179-192
Ingman WV, Robertson SA. TGFbeta1 null mutation causes infertility in male mice associated with testosterone deficiency and sexual dysfunction. Endocrinology 2007 148(8):4032-4043
Ingman WV, Robker RL, Woitiez K, Robertson SA. Null mutation in TGFB1 disrupts ovarian function causing impaired folliculogenesis, oocyte incompetence and early embryo arrest. Endocrinology 2006 147(2):835-845
* Editorial comment in Reproductive Biomedicine Online (2006) titled "Wide disorders in mouse oocytes and embryos after disrupting TGFB1" 12(4):441.
Ingman WV, Wyckoff J, Gouon-Evans V, Condeelis J, Pollard JW. Macrophages promote collagen fibrillogenesis around terminal end buds of the developing mammary gland. Developmental Dynamics 2006 235(12):3222-3229
Ingman WV, Robertson SA. Defining the actions of transforming growth factor beta in reproduction. BioEssays 2002 24(10):904-914
Robertson SA, Ingman WV, O'Leary S, Sharkey DJ, Tremellen KP. Transforming growth factor beta - a mediator of immune deviation in seminal plasma. Journal of Reproductive Immunology 2002 57:109-128
Ingman WV, Owens PC, Armstrong DT. Differential regulation by FSH and IGF-I of extracellular matrix IGFBP-5 in bovine granulosa cells: effect of association with the oocyte. Molecular and Cellular Endocrinology 2000 164:53-58
Entry last updated: Saturday, 30 Jan 2016