Prince Henry’s Institute

 

Matthew Gillespie

 

Appointments

• Director, Prince Henry's Institute

• Honorary Professor, Department of Biochemistry and Molecular Biology, Monash University

 

Profile

Professor Gillespie trained in microbiology and immunology. He was previously an Associate Director at St Vincent's Institute of Medical Research in Melbourne and joined PHI in 2008 as the institute's fourth Director. He has attained international recognition for his research into hormones, bone biology and cancer and his laboratory's focus is upon bone physiology and cancers of bone.

 

Research Interests

Professor Gillespie's research has identified a number of new factors that stop bone loss through inhibition of osteoclast formation, and how T cell-derived cytokines impact upon the formation and resorption of bone.  This has particular relevance for individuals with osteoporosis or rheumatoid arthritis. 

Additionally, his cancer research is focussed on actions of factors derived from cancers, and their relevance to facilitate cancer metastasis to bone.

Professor Gillespie's current interests extend upon the identification of novel inhibitors of bone destruction and how the immune system plays a pivotal role for the action of so many cytokines and growth factors.  The interleukins IL-12, IL-18, IL-23 and IL-33 are of particular interest to the group and their mechanism of action on T cells, osteoclasts and osteoblasts.

Cancer studies are focussed on studying the role of parathyroid hormone-related protein actions upon breast cancers, and determining the actions of factors derived from cancers, and their relevance to facilitate cancer metastasis to bone.

 

Expertise

Bone cell biology and cancers of bone

  

Current Research

• Spread of cancers to bone

• Role of osteoprotegerin in breast cancer growth

• Apo2L/TRAIL as a regulator of cell death in transformed cells

• Prevention of bone loss

• Factors affecting osteoblast differentiation

 

Service to the Scientific Community

• Member of the Council and Science Advisory Committee of the Cancer Council of Victoria

• Member of the Victorian Breast Cancer Research Consortium

• Member of Research Committee of NHMRC Australia

• Member of the Board of the Ovarian Cancer Research Foundation

• Member of Board of Directors the Australian and New Zealand Bone and Mineral Society

• Editorial boards of Arthritis and Rheumatism, Bone, BoneKey, Endocrinology, Journal of Bone and Mineral Research, and an advisor for the Journal of Oral Biosciences

 

Selected Publications

Onan, D., Allan, E.H., Quinn, J.M.W., Gooi, J.H., Pompolo, S., Sims, N.A., Gillespie, M.T.  and Martin, T.J. (2009). The chemokine Cxcl1 is a novel target of PTH/PTHrP in committed osteoblasts. Endocrinology. In press.

McKinstry, W.J., Polekhina, G., Diefenbach-Jagger, H., Sato, K., Onuma, E., Gillespie, M.T., Martin, T.J. and Parker, M.W. (2009). Crystallization of the receptor binding domain of parathyroid hormone-related protein in complex with a neutralizing monoclonal antibody Fab fragment. Acta Crystalographica F65, 336-338.

McKinstry, W.J., Polekhina, G., Diefenbach-Jagger, H., Ho, P.M.W., Sato, K., Onuma, E., Gillespie, M.T., Martin, T.J. and Parker, M.W. (2009). Structural basis for antibody distrimination between two hormones that recognize the parathyroid hormone receptor. .  Journal of Biological Chemistry. 284, 15557-15263

Allan, E.H., Hausler, K.D., Wei, T., Gooi, J.H., Quinn, J.M.W., Crimeen-Irwin, B., Pompolo, S., Sims, N.A., Gillespie, M.T., Onyia, J.E. and Martin T.J. (2008). Ephrin B2 regulation by PTH and PTHrP revealed by molecular profiling in differentiating osteoblasts.  Journal of Bone and Mineral Research. 23, 1170-1181 (IF 6.527). Editorial by Joseph Lorenzo. Journal of Bone and Mineral Research. 23, 1168-1169.

Walker, E., McGregor, N, Poulton I, Pompolo, S., Allan, E.H., Quinn, J.M.W., Gillespie, M.T., Martin T.J. and Sims, N.A. (2008). Carditrophin-1 is and osteoclast-derived stimulus of bone formation required for normal bone remodelling.  Journal of Bone and Mineral Research. 23, 2025-2032. (IF 6.527).

Kartsogiannis, V., Sims, N.A., Quinn, J.M.W., Ly, C., Cipetic, M., Poulton, I.J., Walker, E.C., Saleh, H., McGregor, N.E., Wallace, M.E., Smyth, M.J., Martin, T.J., Zhou, H., Ng, K.W. and Gillespie, M.T. (2008). Osteoclast inhibitory lectin (OCIL), an immune cell product that is required for normal bone physiology in vivo.  Journal of Biological Chemistry. 283, 30850-30860 (IF 5.854).

Quinn, J.M.W., Sims, N.A., Saleh, H., Mirosa, D., Thompson, K., Bouralexis, S., Walker, E.C., Saleh, H., Martin, T.J. and Gillespie, M.T. (2008). Interleukin-23 inhibits osteoclastogenesis indirectly through lymphocytes and is required for the maintenance of bone mass in mice. Journal of Immunology. 181, 5720-5729. (IF 6.387).

Susperregui, A.R.G., Vinals, F., Ho, P.M.W. Gillespie, M.T., Martin, T.J. and Ventura, F. (2008). BMP-2 regulation of PTHrP and osteoclastogenic factors during osteoblast differentiation of C2C12 cells. Journal of Cellular Physiology. 216, 144-152.

Nakamura, A., Ly, C., Cipetic, M., Sims, N.A., Vieusseux, J., Kartsogiannis, V., Bouralexis, S., Saleh, H., Zhou, H., Price, J.T., Martin, T.J., Ng, K.W., Gillespie, M.T. and Quinn, J.M.W. (2007). Osteoclast inhibitory lectin (OCIL) inhibits osteoblast differentiation and function in vitro. Bone. 40, 305-315.

Fisher, J.L., Thomas-Mudge, R.J., Elliott, J., Hards, D.K., Sims, N.A., Slavin, J., Martin, T.J. and Gillespie, M.T. (2006).  Osteoprotegerin over-expression by breast cancer cells enhances orthotopic and osseous tumor growth, and contrasts with that delivered therapeutically.  Cancer Research. 66, 3620-3628

Häusler, K.D., Horwood, N.J., Chuman, Y., Fisher, J.L., Ellis, J., Martin, T.J., Rubin, J.S. and Gillespie, M.T. (2004). Secreted frizzled-related protein-1 inhibits RANKL-dependent osteoclast formation. Journal of Bone and Mineral Research. 19, 1873-1881

Horwood, N.J., Elliott, J., Martin, T.J. and Gillespie, M.T. (2001).  Interleukin-12 alone, and in synergy with interleukin-18, inhibits osteoclast formation in vitro.  Journal of Immunology. 166, 4915-4921

Lam, M.H.C., House, C.M., Tiganis, T., Mitchelhill, K.I., Sarcevic, B., Cures, A., Ramsay, R., Kemp, B.E., Martin, T.J. and Gillespie, M.T. (1999).  Phosphorylation at the cyclin dependent kinases p34cdc2 and p33cdk2 site (Thr85) of parathyroid hormone-related protein (PTHrP) negatively regulates its nuclear localization.  Journal of Biological Chemistry.  274, 18559-18566

Lam, M., Briggs, L.J., Hu, W., Martin, T.J., Gillespie, M.T. and Jans, D.A. (1999).  Importin b recognizes parathyroid hormone-related protein (PTHrP) with high affinity and mediates its nuclear import in the absence of importin a.  Journal of Biological Chemistry.  274, 7391-7398

Thomas, R.J., Guise, T.A., Yin, J.J., Elliott, J., Horwood, N.J., Martin, T.J., and Gillespie, M.T. (1999).  Breast cancer cells interact with osteoblasts to support osteoclast formation.  Endocrinology. 140, 4451-4458