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 in New York, USA, 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 The Queen Elizabeth Hospital which is her current appointment. The Unit investigates 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.
Breast cancer places an incredible burden on Australian women. Every year, around 14,000 Australian women are diagnosed with breast cancer alone - a disease that devastates women's lives and is often fatal.
If we are to prevent and treat breast cancer, we must better understand how the disease develops. Recent research has revealed an exciting new piece of the puzzle: breast cancer may be influenced by immune system cells called macrophages. Akin to the body's housekeepers, macrophages clean up old cellular debris. They also act as bodyguards by sensing invading pathogens and cancer cells - keeping the body safe from disease. Studies in our laboratory and others have demonstrated that macrophages are essential for healthy development of the mammary gland during puberty, menstrual cycling, pregnancy, and lactation. And our recent research suggests that macrophage functions may be associated with a number of well-established breast cancer risk factors. Despite these early clues, little is understood of how macrophages function in breast tissue, how they are regulated, or how they impact on disease states.
Lactation mastitis is an inflammatory breast disease affecting 17-27% of Australian breastfeeding women that causes pain, fever and low milk supply. The challenges posed by this disease lead many women to use supplementary formula, or cease breastfeeding altogether leaving their infants at increased risk of respiratory and gastrointestinal diseases as babies, and non-communicable diseases including heart disease, obesity, diabetes, cancer, allergies, asthma, mental illness and chronic lung, liver and renal diseases as both children and adults. Our recent research has suggested that macrophages play a role in development of this disease.
Our current research pursues new knowledge in how disease state develop in the breast. We explore revolutionary new concepts of how immune cells function in the breast, and how these cells affect breast disease development. In order to gain a comprehensive and thorough understanding, we are researching the issue from four different angles:
1. Menstruation: Each time a woman menstruates, her breast cancer risk increases. What role do macrophages play in this increased risk?
2. Breast density: Women with higher breast density are more likely to develop breast cancer. What role do macrophages play in high mammographic density?
3. Pregnancy: A first full-term pregnancy before the age of 20 halves a woman's lifetime risk of breast cancer. But why? How are macrophages involved in this protective process?
4. Breastfeeding: It has been assumed that lactation mastitis is caused by bacteria, but new research points to inflammation instead. How do macrophages contribute to this inflammation?
Huo CW, Chew G, Hill P, Huang D, Vohora A, Ingman WV, Glynn D, Henderson A, Thompson EW, Britt KL. Human glandular organoid formation in murine engineering chambers after collagenase digestion and flow cytometry isolation of normal human breast tissue single cells. Accepted for publication in Cell Biology International
Liapis V, Zinonos I, Labrinidis A, Hay S, Ponomarev V, Panagopoulos V, Zysk A, DeNichilo M, Ingman W, Atkins GJ, Findlay DM, Zannettino AC, Evdokiou A. Anticancer efficacy of the hypoxia-activated prodrug evofosfamide (TH-302) in osteolytic breast cancer murine models. Cancer Med. 2016 Mar;5(3):534-45
Need EF, Selth LA, Trotta AP, Leach DA, Giorgio L, O'Loughlin MA, Smith E, Gill PG, Ingman WV, Graham JD, Buchanan G. The unique transcriptional response produced by concurrent estrogen and progesterone treatment in breast cancer cells results in upregulation of growth factor pathways and switching from a Luminal A to a Basal-like subtype. BMC Cancer 2015 15:791
Panagopoulos V, Zinonos I, Leach DA, Hay SJ, Liapis V, Zysk A, Ingman WV, DeNichilo MO, Evdokiou A. Uncovering a new role for peroxidase enzymes as drivers of angiogenesis. Int J Biochem Cell Biol. 2015 68:128-38
Huo CW, Chew G, Hill P, Huang D, Ingman W, Hodson L, Brown KA, Magenau A, Allam AH, McGhee E, Timpson P, Henderson MA, Thompson EW, Britt K. Huo CW, Chew G, Hill P, Huang D, Ingman W, Hodson L, Brown KA, Magenau A, Allam AH, McGhee E, Timpson P, Henderson MA, Thompson EW, Britt K. High mammographic density is associated with an increase in stromal collagen and immune cells within the mammary epithelium. Breast Cancer Research. 2015 17:79
Ingman WV, Glynn DJ, Hutchinson MR. Mouse models of mastitis - how physiological are they? International Breastfeeding Journal. 2015 10:12
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: Sunday, 2 Oct 2016