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Home   Researchers   Our researchers
Dr Felicity Davis

Dr Felicity Davis

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    Dr Felicity Davis

    Dr Felicity Davis is a National Health and Medical Research Council (NHMRC) Career Development Fellow and Senior Research Fellow at Mater Research. Felicity heads the new Breast Physiology and Cancer Group. She has authored 20 research articles and reviews including first or senior author manuscripts in Nature Communications, PNAS, Oncogene, Trends in Cell Biology and Trends in Pharmacological Sciences.

    The Breast Physiology and Cancer Group proposes that the key to unlocking the mysteries of breast cancer lies in our understanding of normal breast development, homeostasis and remodelling. The group seeks to understand the cellular hierarchy in the breast and the signalling pathways that regulate adult stem cells. Mammary stem and progenitor cells are believed to be the cell-of-origin of some breast cancers, and are linked to breast cancer heterogeneity and treatment resistance. Thus, a greater understanding of the molecular and phenotypic profiles of these cells will have important implications for the treatment and prevention of breast cancer.

    Felicity also studies the unique capacity of the breast to sustain multiple cycles of pregnancy and lactation. Her work in this field has redefined the process of milk ejection, demonstrating that milk is pumped out of the breast by way of asynchronous, Ca2+-dependent, pulsatile contractions of millions of milk-producing structures. At the end of lactation the mammary gland activates an enormous, coordinated cell death program, to return this organ to a near pre-pregnant state. Felicity hopes that by studying the processes that regulate these “life and death” decisions in the mammary gland under physiological conditions, she will provide brand new avenues for the therapeutic targeting of breast cancer.

    Felicity completed her PhD at the University of Queensland in 2012, before performing postdoctoral research at the National Institute of Environmental Health Sciences (NIEHS/NIH, USA, 2012-14) and the University of Cambridge (UK, 2014-16). In 2016 she returned to Australia to head the Breast Physiology and Cancer Group. She is pharmacist, State Representative for the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) and Homerton College Alumna (Cambridge). She has been awarded almost A$1.5 million in competitive funding as lead investigator (CI-A) and has won over 20 awards, including the ASCEPT Denis Wade J&J Young Investigator Award, Martin Rodbell Award (NIEHS/NIH) and University Medal (UQ). She is a passionate advocate for women in science.

    Research Programs and Groups

    • Cancer Biology and Care - Breast Physiology & Cancer Research

    Research Interests

    • Pharmacology and Pharmaceutical Sciences not elsewhere classified - Pharmacology and Pharmaceutical Sciences
    • Cancer Cell Biology - Oncology and Carcinogenesis

    Projects

    • Breast cancer stem cells: exploring new treatments for breast cancer - Team Role: Principal Investigator
    • Breast cancer stem cells: exploring new treatments for breast cancer - Team Role:

    Funding

    • 2018 - University of Queensland Foundations (UQ Foundation ) - $89,000.00
      Funded ProjectTargeting cancer stem cells: A novel approach to breast cancer treatment
    • 2018 - National Health and Medical Research Council (NHMRC Project Grant) - $442,214.00
      Funded ProjectIdentifying and exploiting novel pharmacological targets for breast cancer treatment
    • 2018 - National Health and Medical Research Council (NHMRC Career Development Fellowship) - $431,000.00
      Funded ProjectIdentifying and exploiting novel pharmacological targets for breast cancer treatment
    • 2017 - University of Queensland (UQ Early Career Researcher) - $34,000.00
      Funded ProjectCalcium signalling and cell death decisions in the postpartum mammary gland: implications for breast cancer treatment
    • 2014 - National Health and Medical Research Council (NHMRC Early Career Fellowship) - $299,382.40
      Funded ProjectInvestigating the cellular requirement for STIM1 phosphorylation and store-operated calcium entry suppression during mitosis: roles in development and cancer

    Publications

    Mammary stem cells: premise, properties, and perspectives
    2017 - Journal Article - DOI: 10.1016/j.tcb.2017.04.001
    Lloyd-Lewis, Bethan, Harris, Olivia B., Watson, Christine J. and Davis, Felicity M.

    Read Abstract

    Adult mammary stem cells (MaSCs) drive postnatal organogenesis and remodeling in the mammary gland, and their longevity and potential have important implications for breast cancer. However, despite intense investigation the identity, location, and differentiation potential of MaSCs remain subject to deliberation. The application of genetic lineage-tracing models, combined with quantitative 3D imaging and biophysical methods, has provided new insights into the mammary epithelial hierarchy that challenge classical definitions of MaSC potency and behaviors. We review here recent advances – discussing fundamental unresolved properties of MaSC potency, dynamics, and plasticity – and point to evolving technologies that promise to shed new light on this intractable debate. Elucidation of the physiological mammary differentiation hierarchy is paramount to understanding the complex heterogeneous breast cancer landscape.


    Oncosis and apoptosis induction by activation of an overexpressed ion channel in breast cancer cells
    2017 - Journal Article - DOI: 10.1038/onc.2017.234
    Peters, A. A., Jamaludin, S. Y. N., Yapa, K. T. D. S., Chalmers, S., Wiegmans, A. P., Lim, H. F., Milevskiy, M. J. G., Azimi, I., Davis, F. M., Northwood, K. S., Pera, E., Marcial, D. L., Dray, E., Waterhouse, N. J., Cabot, P. J., Gonda, T. J., Kenny, P. A., Brown, M. A., Khanna, K. K., Roberts-Thomson, S. J. and Monteith, G. R.

    no abstract available


    The ins and outs of calcium signalling in lactation and involution: implications for breast cancer treatment
    2017 - Journal Article - DOI: 10.1016/j.phrs.2016.12.007
    Davis, Felicity M.

    Read Abstract

    The mammary epithelium is highly responsive to hormonal and non-hormonal signalling cues for physiological growth, function and tissue remodelling. Whilst steroid hormones freely diffuse across the cell membrane to bind to intracellular hormone receptors, cell-impermeable ligands, including many peptide hormones, growth factors and cytokines, bind to receptors on the plasma membrane and relay their message via the specific activation of intracellular signal transduction pathways. A signalling pathway that is indispensable for decoding many extracellular signals into cellular responses is calcium (Ca2+). Changes in the expression of specific Ca2+ channels, pumps and binding proteins may therefore greatly alter the nature of the cellular response to various growth, morphogenetic and cell death stimuli. This review summarises changes in the expression, localisation and function of key Ca2+ channels and pumps in mammary epithelial cells during lactation and discusses how this altered Ca2+ handling may later expose these cells to targeted cell death during post-lactational involution. A greater understanding of the processes regulating the growth, death and regeneration of the mammary epithelium under physiological conditions may provide important insights into the proliferation and survival mechanisms underpinning malignant growth. The therapeutic manipulation of specific calcium signalling pathways in breast cancer cells to control aberrant cell proliferation and/or turnover represents an aim for the future.


    Altered purinergic receptor-Ca2+ signaling associated with hypoxia-induced epithelial-mesenchymal transition in breast cancer cells
    2016 - Journal Article - DOI: 10.1016/j.molonc.2015.09.006
    Azimi, Iman, Beilby, Hannah, Davis, Felicity M., Marcial, Daneth L., Kenny, Paraic A., Thompson, Erik W., Roberts-Thomson, Sarah J. and Monteith, Gregory R.

    Read Abstract

    Hypoxia is a feature of the microenvironment of many cancers and can trigger epithelial-mesenchymal transition (EMT), a process by which cells acquire a more invasive phenotype with enriched survival. A remodeling of adenosine 5′-triphosphate (ATP)-induced Ca2+ signaling via purinergic receptors is associated with epidermal growth factor (EGF)-induced EMT in MDA-MB-468 breast cancer cells. Here, we assessed ATP-mediated Ca2+ signaling in a model of hypoxia-induced EMT in MDA-MB-468 cells. Like EGF, hypoxia treatment (1% O2) was also associated with a significant reduction in the sensitivity of MDA-MB-468 cells to ATP (EC50 of 0.5 μM for normoxic cells versus EC50 of 5.8 μM for hypoxic cells). Assessment of mRNA levels of a panel of P2X and P2Y purinergic receptors following hypoxia revealed a change in levels of a suite of purinergic receptors. P2X4, P2X5, P2X7, P2Y1 and P2Y11 mRNAs decreased with hypoxia, whereas P2Y6 mRNA increased. Up-regulation of P2Y6 was a common feature of both growth factor- and hypoxia-induced models of EMT. P2Y6 levels were also significantly increased in basal-like breast tumors compared to other subtypes and breast cancer patients with higher P2Y6 levels showed reduced overall survival rates. P2Y6 siRNA-mediated silencing and the P2Y6 pharmacological inhibitor MRS2578 reduced hypoxia-induced vimentin protein expression in MDA-MB-468 cells. P2Y6 inhibition also reduced the migration of mesenchymal-like MDA-MB-231 breast cancer cells. The up-regulation of P2Y6 appears to be a common feature of the mesenchymal phenotype of breast cancer cells and inhibition of this receptor may represent a novel therapeutic target in breast cancer metastasis.


    Gaq proteins: molecular pharmacology and therapeutic potential
    2016 - Journal Article - DOI: 10.1007/s00018-016-2405-9
    Kamato, Danielle, Mitra, Partha, Davis, Felicity, Osman, Narin, Chaplin, Rebecca, Cabot, Peter J., Afroz, Rizwana, Thomas, Walter, Zheng, Wenhua, Kaur, Harveen, Brimble, Margaret and Little, Peter J.

    Read Abstract

    Seven transmembrane G protein-coupled receptors (GPCRs) have gained much interest in recent years as it is the largest class among cell surface receptors. G proteins lie in the heart of GPCRs signalling and therefore can be therapeutically targeted to overcome complexities in GPCR responses and signalling. G proteins are classified into four families (Gi, Gs, G12/13 and Gq); Gq is further subdivided into four classes. Among them Gαq and Gαq/11 isoforms are most crucial and ubiquitously expressed; these isoforms are almost 88% similar at their amino acid sequence but may exhibit functional divergences. However, uncertainties often arise about Gαq and Gαq/11 inhibitors, these G proteins might also have suitability to the invention of novel-specific inhibitors for each isoforms. YM-254890 and UBO-QIC are discovered as potent inhibitors of Gαq functions and also investigated in thrombin protease-activated receptor (PAR)-1 inhibitors and platelet aggregation inhibition. The most likely G protein involved in PAR-1 stimulates responses is one of the Gαq family isoforms. In this review, we highlight the molecular structures and pharmacological responses of Gαq family which may reflect the biochemical and molecular role of Gαq and Gαq/11. The advanced understanding of Gαq and Gαq/11 role in GPCR signalling may shed light on our understanding on cell biology, cellular physiology and pathophysiology and also lead to the development of novel therapeutic agents for a number of diseases.


    Imaging the mammary gland and mammary tumours in 3D: optical tissue clearing and immunofluorescence methods
    2016 - Journal Article - DOI: 10.1186/s13058-016-0754-9
    Lloyd-Lewis, Bethan, Davis, Felicity M., Harris, Olivia B., Hitchcock, Jessica R., Lourenco, Filipe C., Pasche, Mathias and Watson, Christine J.

    Read Abstract

    Background: High-resolution 3D imaging of intact tissue facilitates cellular and subcellular analyses of complex structures within their native environment. However, difficulties associated with immunolabelling and imaging fluorescent proteins deep within whole organs have restricted their applications to thin sections or processed tissue preparations, precluding comprehensive and rapid 3D visualisation. Several tissue clearing methods have been established to circumvent issues associated with depth of imaging in opaque specimens. The application of these techniques to study the elaborate architecture of the mouse mammary gland has yet to be investigated.

    Methods: Multiple tissue clearing methods were applied to intact virgin and lactating mammary glands, namely 3D imaging of solvent-cleared organs, see deep brain (seeDB), clear unobstructed brain imaging cocktails (CUBIC) and passive clarity technique. Using confocal, two-photon and light sheet microscopy, their compatibility with whole-mount immunofluorescent labelling and 3D imaging of mammary tissue was examined. In addition, their suitability for the analysis of mouse mammary tumours was also assessed.

    Results: Varying degrees of optical transparency, tissue preservation and fluorescent signal conservation were observed between the different clearing methods. SeeDB and CUBIC protocols were considered superior for volumetric fluorescence imaging and whole-mount histochemical staining, respectively. Techniques were compatible with 3D imaging on a variety of platforms, enabling visualisation of mammary ductal and lobulo-alveolar structures at vastly improved depths in cleared tissue.

    Conclusions: The utility of whole-organ tissue clearing protocols was assessed in the mouse mammary gland. Most methods utilised affordable and widely available reagents, and were compatible with standard confocal microscopy. These techniques enable high-resolution, 3D imaging and phenotyping of mammary cells and tumours in situ, and will significantly enhance our understanding of both normal and pathological mammary gland development.


    Male infertility in mice lacking the store-operated Ca(2+) channel Orai1
    2016 - Journal Article - DOI: 10.1016/j.ceca.2016.02.007
    Davis, Felicity M., Goulding, Eugenia H., D'Agostin, Diane M., Janardhan, Kyathanahalli S., Cummings, Connie A., Bird, Gary S., Eddy, Edward M. and Putney, James W.

    Read Abstract

    Store-operated calcium entry (SOCE) is an important Ca2+ influx pathway in somatic cells. In addition to maintaining endoplasmic reticulum (ER) Ca2+ stores, Ca2+ entry through store-operated channels regulates essential signaling pathways in numerous cell types. Patients with mutations in the store-operated channel subunit ORAI1 exhibit defects in store-operated Ca2+ influx, along with severe immunodeficiency, congenital myopathy and ectodermal dysplasia. However, little is known about the functional role of ORAI1 in germ cells and reproductive function in mice, or in men, since men with loss-of-function or null mutations in ORAI1 rarely survive to reproductive age. In this study, we investigated the role of ORAI1 in male reproductive function. We reveal that Orai1−/− male mice are sterile and have severe defects in spermatogenesis, with prominent deficiencies in mid- to late-stage elongating spermatid development. These studies establish an essential in vivo role for store-operated ORAI1 channels in male reproductive function and identify these channels as potential non-steroidal regulators of male fertility.


    Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny
    2016 - Journal Article - DOI: 10.1038/ncomms13053
    Davis, Felicity M., Lloyd-Lewis, Bethan, Harris, Olivia B., Kozar, Sarah, Winton, Douglas J., Muresan, Leila and Watson, Christine J.

    Read Abstract

    The mammary gland undergoes cycles of growth and regeneration throughout reproductive life, a process that requires mammary stem cells (MaSCs). Whilst recent genetic fate-mapping studies using lineage-specific promoters have provided valuable insights into the mammary epithelial hierarchy, the true differentiation potential of adult MaSCs remains unclear. To address this, herein we utilize a stochastic genetic-labelling strategy to indelibly mark a single cell and its progeny in situ, combined with tissue clearing and 3D imaging. Using this approach, clones arising from a single parent cell could be visualized in their entirety. We reveal that clonal progeny contribute exclusively to either luminal or basal lineages and are distributed sporadically to branching ducts or alveoli. Quantitative analyses suggest that pools of unipotent stem/progenitor cells contribute to adult mammary gland development. Our results highlight the utility of tracing a single cell and reveal that progeny of a single proliferative MaSC/progenitor are dispersed throughout the epithelium.


    The functions of store-operated calcium channels
    2016 - Journal Article - DOI: 10.1016/j.bbamcr.2016.11.028
    Putney, James W., Steinckwich-Besancon, Natacha, Numaga-Tomita, Takuro , Davis, Felicity M., Desai, Pooja N., D'Agostin, Diane M., Wu, Shilan and Bird, Gary S.

    Read Abstract

    Store-operated calcium channels provide calcium signals to the cytoplasm of a wide variety of cell types. The basic components of this signaling mechanism include a mechanism for discharging Ca2+ stores (commonly but not exclusively phospholipase C and inositol 1,4,5-trisphosphate), a sensor in the endoplasmic reticulum that also serves as an activator of the plasma membrane channel (STIM1 and STIM2), and the store-operated channel (Orai1, 2 or 3). The advent of mice genetically altered to reduce store-operated calcium entry globally or in specific cell types has provided important tools to understand the functions of these widely encountered channels in specific and clinically important physiological systems. This review briefly discusses the history and cellular properties of store-operated calcium channels, and summarizes selected studies of their physiological functions in specific physiological or pathological contexts. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.


    A potential role for Janus protein tyrosine kinases in the regulation of epithelial-mesenchymal transition in a model of epidermal growth factor induced breast cancer epithelial-mesenchymal transition
    2015 - Conference Paper - DOI: 10.1158/1538-7445.sabcs14-p2-07-05
    Stewart, Teneale A., Azimi, Iman, Davis, Felicity M., Thompson, Erik W., Brooks, Andrew J., Roberts-Thomson, Sarah J. and Monteith, Gregory R.

    no abstract available

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    Awards

    • Foundation Research Excellence Award (FREA)
      Awarding Body: University of Queensland Foundation
      Year awarded: 2017

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