Our research goal is to understand how specific tissues, such as bone, control the fate of cancer cells – regulating their survival, dormancy and subsequent activation into metastatic tumours. We aim to generate new therapies for early intervention in metastatic disease and prevention of disease recurrence.
Our group has developed a novel intravital imaging technique which allows, for the first time, visualisation and fate tracking of dormant and actively growing tumour cells within the bone marrow environment, as well as visualisation of bone cells in real time in vivo.
In addition to revealing previously unappreciated dynamics in bone cell biology, these studies have revealed control of tumour cell behaviour by bone cells; highlighting the local control of tumour processes including long-term dormancy, chemo-resistance, and deadly disease relapse.
Combined with our extensive experience using therapeutic agents to modulate bone cell activity in vivo, we are uniquely placed to define how these agents can best be repurposed to prevent tumour-induced bone destruction and, more importantly, how their modification of the bone environment can also prevent tumour growth. Ultimately, our team aims to improve quality of life and survival for patients with metastatic bone disease or multiple myeloma.
McDonald MM, Fairfield H, Falank C, Reagan MR. Adipose, Bone, and Myeloma: Contributions from the Microenvironment. Calcif Tissue Int. 2016 Jun 24. [Epub]
Martin TJ, McDonald MM, Croucher PI. Bone metastasis: The importance of the Neighborhood. Nature Reviews Cancer. June 16(4) p373. 2016.
McDonald MM, Lawson MA* Kovacic N, Khoo WH, Terry RL, Down J, Paklan W, Paton Hough J, Fellows C, Pettitt JA, Dear TN, Van Valckenbourgh E, Baldock PA, Rogers MJ, Eaton CL, Vanderkerken K, Pettitt AR, Quinn JMW, Zannettino ACW, Phan TG, Crouchr PI. Osteoclasts Control Re-activation of Dormant Myeloma Cells by Remodeling the Endosteal Niche. Nature Communications Dec 2015.
Morse A, Yu NYC, Mikulec K, Peacock L, Kramer I, Kneissel M, McDonald MM, Little DG. (equal last author). Endochondral fracture healing with external fixation in the Sost knockout mouse results in earlier fibrocartilage callus removal and increased bone volume fraction and strength. Bone 2015 Feb;71:155-63.
Morse A, McDonald MM, Kelly NH, Melville KM, Schindeler A, Kramer I, Kneissel M, van der Meulen MCH, and Little DG. Mechanical load increases in bone formation via a Sclerostin-independent pathway. J Bone and Mineral Research. 2014 Nov;29(11):2456-67
El-Hoss J, Kolind M, Jackson MT, Deo N, Mikulec K, McDonald MM, Little CB, Little DG, Schindeler A. Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib). Bone. 2014 Feb;59:151-61
Kovacic N, Croucher PI, McDonald MM. Signaling between tumor cells and the host bone marrow microenvironment Calcif Tissue Int. 2014 Jan;94(1):125-39.
Bosemark P, Isaksson H, McDonald MM, Little DG, Tägil M. Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength. Acta Orthopaedica, 2013 Feb;84(1):106-11
McDonald MM, Morse A, Mikulec K, Peacock L, Baldock P, Kostenuik PJ, Little DG. Osteoclasts are redundant during MMP driven endochondral fracture repair, but essential to hard callus remodelling. J Bone Miner Res. 2013 Jul;28(7):1550-60
McDonald MM, Birke O, Morse A, Mikulec, K, Peacock L, Baldock P, Min Liu, Hua Zhu Ke, Little DG. Inhibition of Sclerostin by Systemic Treatment with Sclerostin Antibody Enhances Healing of Proximal Tibial Defects in Ovariectomized Rats. Journal of Orthopaedic Research Oct;30(10):1541-8 2011.
More Garvan Publications
Staff in the Group
Laboratory Technician 1-3