Dr Michelle McDonald

Group Leader - Bone Microenvironment

Dr Michelle McDonald

Dr Michelle McDonald’s research careers spans over 19 years, attaining her PhD in 2008 at The Kids Research Institute, Westmead, she is currently Group Leader of the Bone Microenvironment Group at The Garvan Institute of Medical Research, Sydney, Australia. Through the development of a novel intravi

Biography

Dr Michelle McDonald’s research careers spans over 19 years, attaining her PhD in 2008 at The Kids Research Institute, Westmead, she is currently Group Leader of the Bone Microenvironment Group at The Garvan Institute of Medical Research, Sydney, Australia. Through the development of a novel intravital imaging technique her research has allowed, for the first time, visualisation and fate tracking of dormant and actively growing tumour cells within living bone, as well as visualisation of bone cells in real time. This approach has revealed previously unappreciated bone cell dynamics and interactions, thereby advancing our fundamental understanding of osteoclast biology, and uncovering mechanisms behind unexpected clinical responses to anti-resorptive therapies. In addition, bone cell regulation of tumour cell behaviour, including dormancy, chemo-resistance, and disease relapse, has been demonstrated using this technique. Combined with her extensive experience using therapeutic agents to modulate bone cell activity in vivo, her group is working to define how these agents can be repurposed to prevent tumour-induced bone destruction and prevent tumour growth through regulating the bone micro-environment. This work has recently attracted a number of awards, grants and international invitations to speak, and spans collaborations with academic and industry partners internationally.

 

Dr McDonald has always worked closely with clinician scientists, which has influenced the development of her research towards clinically translatable outcomes. Michelle regularly perform peer reviews, sits on the editorial board for the Journal of Bone Oncology and Clinical Reviews in Bone and Mineral Research and has also held positions on international scientific committees and editorial boards (IBMS, ASBMR IFMRS and ANZBMS). Her research interests have also allowed multiple opportunities to work with industry and pharmaceutical companies, and more recently form active collaborations within Australia and with groups form the UK and the USA.

Dr Michelle McDonald’s research careers spans over 19 years, attaining her PhD in 2008 at The Kids Research Institute, Westmead, she is currently Group Leader of the Bone Microenvironment Group at The Garvan Institute of Medical Research, Sydney, Australia. Through the development of a novel intravital imaging technique her research has allowed, for the first time, visualisation and fate tracking of dormant and actively growing tumour cells within living bone, as well as visualisation of bone cells in real time. This approach has revealed previously unappreciated bone cell dynamics and interactions, thereby advancing our fundamental understanding of osteoclast biology, and uncovering mechanisms behind unexpected clinical responses to anti-resorptive therapies. In addition, bone cell regulation of tumour cell behaviour, including dormancy, chemo-resistance, and disease relapse, has been demonstrated using this technique. Combined with her extensive experience using therapeutic agents to modulate bone cell activity in vivo, her group is working to define how these agents can be repurposed to prevent tumour-induced bone destruction and prevent tumour growth through regulating the bone micro-environment. This work has recently attracted a number of awards, grants and international invitations to speak, and spans collaborations with academic and industry partners internationally.

 

Dr McDonald has always worked closely with clinician scientists, which has influenced the development of her research towards clinically translatable outcomes. Michelle regularly perform peer reviews, sits on the editorial board for the Journal of Bone Oncology and Clinical Reviews in Bone and Mineral Research and has also held positions on international scientific committees and editorial boards (IBMS, ASBMR IFMRS and ANZBMS). Her research interests have also allowed multiple opportunities to work with industry and pharmaceutical companies, and more recently form active collaborations within Australia and with groups form the UK and the USA.

Awards and Honours

1. Bone Health Foundation/ANZBMS 2021-22 Grant in Aide.
2. Cancer Council NSW Project Grant 2020-2022
3. Cancer Institute NSW Career Development Fellowship 2019-2021
4. ASBMR Rising Star Award 2019
5. Weizmann-Garvan Collaborative Research Program Grant 2019.
6. CHAMP Young Pioneer Award, Garvan Institute, 2018
7. Amgen Outstanding Abstract Award. ANZBMS Brisbane 2017.
8. Amgen Outstanding Abstract Award. ANZBMS Gold Coast 2016.
9. ANZBMS Kaye Ibbertson Award for Bone and Mineral Medicine. 2016
10. Amgen Outstanding Abstract Award. ANZBMS Hobart November 2015.

Education

2008 – PhD, University of Technology Sydney - Australia
2000 – BMedSc, University of Technology Sydney - Australia

Fundings

Ongoing research support

Bone Health Foundation – ANZBMS Grant in

Duration: 2021/2022

Title: Prevention of Rebound Bone loss and Fracture Induced by Denosumab Withdrawal

Ernest Heine Foundation Project Funding -

Duration: 2020-2023

Title: Cellular Control of Bone Loss

National Institutes of Health R37 Project Grant

Duration: 2020-2024

Title: Bone-Targeted Therapies to Improve Bone Health and Prevent Relapse in Multiple

Myeloma

Ian Potter Foundation Equipment Grant

Duration: 2020

Title: ‘[MR] High-speed 2D/3D microscope imaging platform with image-enhancing capability for disease modelling and testing novel therapies’

Cancer Council NSW Project Grant

Duration: 2020-2022

Title: Live tissue imaging reveals insight into bone and tumour cell communication: Implications for bone targeted therapeutic control of cancer growth in bone

Weizmann-Garvan Centre for Cellular Genomics Collaborative Research Program Grant

Duration: 2019-2021

Title: Decoding the cellular dynamics and dissemination patterns of plasma cells within intact bones

ASBMR Rising Star Award 

Duration 2019-2021

Title: Intravital imaging reveals novel bone cell behavior: Implications for rebound bone loss following cessation anti-RANKL therapy

AMR Equipment Grant

Duration: 2019

Title: Incucyte Gas mixer

Cancer Institute NSW Career Development Fellowship

Duration: 2019-2021

Title: Tumor-bone cell interactions: An opportunity to harness the microenvironment to overcome metastatic disease

CHAMP Young Pioneer Award

Duration: 2018/19

Title: Intravital imaging reveals novel bone cell behavior: Implications for the treatment of bone metastatic cancers.

 

Completed research support

Cancer Council NSW project grant.

Duration: 2016-2018 

Title: Anti-Sclerostin – a novel, dual action agent to treat multiple myeloma.

Amgen Industry Partner Funded Research Agreement

Duration: 2017-2018

Title: Combining RANKL Inhibition and Carfilzomib Treatment to Reduce Myeloma Burden in Multiple Myeloma

Selected Publications

  1. Ryan C Chai and Michelle M McDonald. Visualisation of tumour cells in bone in vivo at single-cell resolution. Bone 2021, Accepted 11th May 2021.
  2. Michelle M McDonald, Albert Kim, Bridie Mulholland, Martina Rauner. The Osteoclast Revisited. Journal of Bone and Mineral Research Plus, 2021 Accepted 10th
  3. Albert Kim, Michelle M McDonald, Christian Girgis. The relationship between sleep and bone: Strange bedfellows? Current Opinion in Endocrine and Metabolic Research., June 2021. 8:236-242
  4. Michelle M McDonald; Weng Hua Khoo; Pei Ying Ng; Ya Xiao; Jad Zammerli; Peter Thatcher; Wunna Kyaw; Karrnan Pathmanandavel; Abigail Grootveld; Imogen Moran; Danyal Butt; Akira Nguyen; Sean Warren; Mate Biro; Natalie Butterfield; Siobhan Guilfoyle; Davide Komla-Ebr; Michael Dack; Hannah F. Dewhurst; John G. Logan; Yongxiao Li; Sindhu Mohanty; Niall Byrne; Rachael Terry; Marija Simic; Ryan Chai; Julian Quinn; Scott Youlten; Jessica A. Pettitt; David Abi-Hanna; Rohit Jain; Wolfgang Weninger; Mischa Lundberg; Shuting Sun; Hal Ebetino; Paul Timpson; Woei Ming Lee; Paul Baldock; Michael Rogers; Robert Brink; Graham R. Williams; Duncan Bassett; John Kemp; Nathan J. Pavlos; Peter I. Croucher; Tri G Phan Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption. Cell March 4 2021;184(5):1330-1347.
  5. Scott E. Youlten, John P. Kemp, John G. Logan, Elena J. Ghirardello, Claudio M. Sergio, Michael R. G. Dack, Siobhan E. Guilfoyle, Victoria D. Leitch, Natalie C. Butterfield, Davide Komla-Ebri, Ryan C. Chai, Alexander P. Corr, James T. Smith, Sindhu Mohanty, John A. Morris, Michelle M. McDonald, Julian M. W. Quinn, Amelia R. McGlade, Nenad Bartonicek, Matt Jansson, Konstantinos Hatzikotoulas, Melita D. Irving, Ana Beleza-Meireles, Fernando Rivadeneira, Emma Duncan, J. Brent Richards, David J. Adams, Christopher J. Lelliott, Robert Brink, Tri Giang Phan, John A. Eisman, David M. Evans,  Eleftheria Zeggini, Paul A. Baldock,  H. Duncan Bassett,  Graham R. Williams, Peter I. Croucher. Osteocyte Transcriptome Mapping Identifies a Molecular Landscape Controlling Skeletal Homeostasis and Susceptibility to Skeletal Disease. Nature Communications 2021 May 5;12(1):2444
  6. Heather Fairfield, Amel Dudakovic, Casper M. Khatib, Mariah Farrell, Samantha Costa, Carolyne Falank, Maja Hinge, Connor Murphy, Victoria DeMambro, Jessica A. Pettitt, Christine W. Lary, Heather Driscoll, Michelle M. McDonald, Thomas L. Andersen, Moustapha Kassem5, Andre J. van Wijnen, Abbas Jafari, Michaela R. Reagan Myeloma-modified adipocytes exhibit metabolic dysfunction and a senescence-associated secretory phenotype (SASP). Cancer Res 2020 Nov 20; canres.1088.2020. doi: 10.1158/0008-5472.CAN-20-1088.
  7. Jähn K, Wölfel EA, Jobke B, Riedel C, Hellmich M, Werner M, McDonald MM, Busse B. Elevated bone hardness under denosumab treatment, with persisting lower osteocyte viability during discontinuation. Front Endocrinol (Lausanne) 2020 May 15;11:250. doi: 10.3389/fendo.2020.00250. eCollection 2020
  8. Owen K, Gearing L, Zanker D, Brockwell N, Khoo W, Roden D, Cmero M, Mangiola S, Hong M, Spurling A, McDonald MM….. Croucher PI, Hovens C, Parker B. Prostate cancer cell-intrinsic interferon signaling regulates dormancy and metastatic growth in bone. EMBO Reports 2020 June 4;21(6):e50162
  9. Simic M, McDonald MM. Myeloma Bone Disease Book Chapter, Encyclopaedia of Bone Biology. June 2020. Book ISBN: 9780128140819
  10. Morse A, McDonald MM, Mikulec K, Schindeler A, Munns CF, Little DG. Pretreatment with Pamidronate Decreases Bone Formation but Increases Callus Bone Volume in a Rat Closed Fracture Model. Calcif Tissue Int. 2019 Oct 1. doi: 10.1007/s00223-019-00615-z. [Epub ahead of print] PMID: 31578632
  11. Morse A, Ko F, McDonald MM, Lee L, Schindeler A, van der Meulen MCH, Little DG. Increased anabolic bone response in Dkk1 KO mice following tibial compressive loading. 2020 Feb. doi: 10.1016/j.bone.2019.115054. PMID: 31521827
  12. Weng Hua Khoo, Guy Ledergor, Assaf Weiner, Daniel Roden, Rachael Terry, Michelle M McDonald, Ryan Chai, Kim Veirman, Katie Owen, Khatora Opperman…..Tri Phan, and Peter Croucher. A Niche-Dependent Myeloid Transcriptome Signature Defines Dormant Myeloma Cells. 2019 Jul 4;134(1):30-43. doi: 10.1182/blood.2018880930. Epub 2019 Apr 25.PMID: 31023703
  13. Konstantin Horas, Yu Zheng , Colette Fong-Yee, Eugenie Macfarlane, Jeline Manibo, Yunzhao Chen, Jeremy Qiao, Mingxuan Gao, Nancy Haydar, Michelle M. McDonald, Peter I. Croucher, Hong Zhou, Markus J. Seibel. Loss of the vitamin D receptor in human breast cancer cells promotes epithelial to mesenchymal cell transition and skeletal colonisation. J Bone Miner Res. 2019 Sep;34(9):1721-1732. doi: 10.1002/jbmr.3744. Epub 2019 Jun 25.
  14. Niall M Byrne, Matthew A Summers, and Michelle M McDonald. Tumor Cell Dormancy and Reactivation in Bone: Skeletal Biology and Therapeutic Opportunities JBMR Plus 2019 Mar; 3(3): e10125. PMID: 30918917
  15. Morse A, Cheng TL, Schindeler A, McDonald MM, Mohanty ST, Kneissel M, Kramer I, Little DG. Dkk1 KO Mice Treated with Sclerostin Antibody Have Additional Increases in Bone Volume. Calcif Tissue Int. 2018 May 29. doi: 10.1007/s00223-018-0420-6.
  16. Haydar, N. & McDonald, M.M. Tumor Cell Dormancy—a Hallmark of Metastatic Growth and Disease Recurrence in Bone Curr Mol Bio Rep 2018 June;20(2) DOI:10.1007/s40610-018-0088-8
  17. Morse A, Schindeler A, McDonald MM, Kneissel M, Kramer I, Little DG. Sclerostin Antibody Augments the Anabolic Bone Formation Response in a Mouse Model of Mechanical Tibial Loading. J Bone Miner Res. 2018 Mar;33(3):486-498.
  18. McDonald MM, Morse A, Schindeler A, Mikulec K, Peacock L, Cheng T, Bobyn J, Lee L, Baldock P.A, Croucher P.I. Tam PPL, Little DG. Homozygous Dkk1 knockout mice exhibit high bone mass phenotype due to increased bone formation. Calcif Tissue Int. 2018 Jan;102(1):105-116.
  19. McDonald MM, Delgado-Calle Jesus. Sclerostin: an emerging target for the treatment of cancer-induced bone disease. Current Osteoporosis Reports. 2017 Dec;15(6):532-541. doi: 10.1007/s11914-017-0403-y.
  20. McDonald MM, Morse A, Birke O, Yu NY, Mikulec K, Peacock L, Schindeler A, Liu M, Ke HZ, Little DG. Sclerostin antibody enhances bone formation in a rat model of distraction osteogenesis. J Orthop Res. 2017 Sep 8
  21. Ryan C. Chai, McDonald MM, Rachael L. Terry, Nataša Kovačić, Jenny M. Down, Jessica A. Pettitt, Sindhu T. Mohanty, Shruti Shah, Gholamreza Haffari, Jiake Xu, Matthew T. Gillespie, Michael J. Rogers, John T. Price, Peter I. Croucher1 * and Julian M.W. Quinn*. Melphalan modifies the bone microenvironment by enhancing osteoclast formation. 2017 Jul 10;8(40):68047-68058.
  22. Fairfield H, Falank C, Harris E, Demambro V, McDonald MM, Pettitt JA, Mohanty ST, Croucher P, Kramer I, Kneissel M, Rosen CJ, Reagan MR. The skeletal cell-derived molecule sclerostin drives bone marrow adipogenesis. J Cell Physiol. 2018 Feb;233(2):1156-1167.
  23. McDonald MM, Reagan MR, Youlten SE, Mohanty ST, Seckinger A, Terry RL, Pettitt JA, Simic MK, Cheng TL, Morse A, Le LMT, Abi-Hanna D, Kramer I, Falank C, Fairfield H, Ghobrial IM, Baldock PA, Little DG, Kneissel M, Vanderkerken K, Bassett JHD, Williams GR, Oyajobi BO, Hose D, Phan TG, Croucher PI. Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma. 2017 Jun 29;129(26):3452-3464.
  24. Morse A, McDonald MM, Schindeler A, Peacock L, Mikulec K, Cheng TL, Liu M, Ke HZ, Little DG. Sclerostin Antibody Increases Callus Size and Strength but does not Improve Fracture Union in a Challenged Open Rat Fracture Model. Calcif Tissue Int. 2017 Aug;101(2):217-228
  25. McDonald MM, Fairfield H, Falank C, Reagan MR. Adipose, Bone, and Myeloma: Contributions from the Microenvironment. Calcif Tissue Int. 2017 May;100(5):433-448
  26. Martin TJ, McDonald MM, Croucher PI. Bone metastasis: The importance of the Neighborhood. Nature Reviews Cancer. June 16(4) p373. 2016.
  27. 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 3;6:8983.
  28. 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.

Invited Book chapters:

  1. Marija K Simic and Michelle M McDonald. Myeloma Bone Disease, Encyclopaedia of Bone Biology 1st Edition June 2020

Summers MA, McDonald MM, Croucher PI. Cancer Cell Dormancy in Metastasis. Cold Spring Harb Perspect Med. 2020 Apr. pii: a037556. doi: 10.1101/cshperspect.a037556.

Amanat N, McDonald M, Godfrey C, Bilston L, Little DG. Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair. J Bone and Min Res. J Bone and Mineral Research. 2007 June 22(6):867-76.