Prince Henry’s Institute

 

Steve Bouralexis

 

Profile

Dr Bouralexis gained his PhD in medicine from the University of Adelaide and in 2003 joined Professor Matthew Gillespie's group, then based at St Vincent's Institute of Medical Research.

In 2008 Dr Bouralexis joined Prince Henry's Institute where he continues his research interests into the functional characterisation of PTHrP, with particular reference to its role in sensitising cancer cells to the apoptotic effects of TNF-related Apoptosis Inducing Ligand (TRAIL/Apo2L).

 

Research Interests

Ligands and receptors of the tumour necrosis factor (TNF) super-families are examples of signal transducers whose integrated actions control and orchestrate immune and inflammatory responses, the development of secondary lymphoid organs and the regulation of programmed cell death (apoptosis).

Despite their varied and pleiotropic actions, members of the TNF ligand and receptor family have remarkably similar structures, and their mode of interaction is conserved. The TNF super-family comprises of 19 primarily membrane-bound proteins and 29 receptors.

Our laboratory is interested in understanding the processes that regulate apoptotic signaling in breast cancer cells. In particular we are focusing on the role that PTHrP plays in the sensitisation of breast cancer cells to the apoptotic effects of TRAIL.

We are also interested in the roles of:

• TRAIL receptors, which mediate the access and availability of TRAIL to bind and elicit either a pro- or anti-apoptotic signal

• Intracellular proteins that antagonise or facilitate this process

• Novel gene targets which might determine whether a cancer will respond to TRAIL treatment

These studies are important, as dysregulation of these processes resulting in either an excess or a deficiency in TRAIL and its associated receptors leads to human disease.

 

Expertise

Breast cancer biology, apoptosis, TRAIL/Apo2L, molecular and cellular biology, immunofluorescence, cell culture, flow cytometry, micro-arrays.

 

Recent Achievements

• 2008/2009 - Funding, National Breast Cancer Foundation

• 2008/2009 - Funding, Cancer Council of Victoria

• 2004 - Awarded NHMRC Peter Doherty Training Fellowship

 

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

 

Selected Publications

Quinn, M.W.J., Sims, A.N., Saleh, H., Mirosa, D., Thompson, K., Bouralexis, S., Walker, E.C., Martin, T.J., Gillespie, M.T. (2008) Interleukin-23 Inhibits Osteoclastogenesis Indirectly through Lymphocytes and is Required for the Maintenance of Bone Mass in Mice. J Immunol.  Oct 15;181(8):5720-9.

Zopf, S*., Neureiter, D*., Bouralexis., S*. Glaser., KB., Okamoto, K., Ganslmayer, M., Hahn, EG., Ocker, M., Herold, C. (2007) Differential Response of P53 and p21 on HDAC-inhibitor mediated apoptosis in HCT116 colon cancer cells in vitro and in vivo. Int J Oncol; 31(6):1391-402.  *joint first authors

Nakamura, A., Ly, C., Sims, NA., Kartsogiannis, V., Bouralexis, S., Saleh, H., Zhou, H., Martin, TJ., Ng, KW., Gillespie, MT., Quinn, J. (2007) Osteoclast inhibitory lectin (OCIL) inhibits osteoblast differentiation and function in vitro. Bone; 40(2): 305-315.

Thai, L.M., Labrinidis, A., Hay, S., Liapis, V., Bouralexis, S., Welldon, K., Coventry, B., Findlay, D.M., Evdokiou., A. (2006) Apo2L/TRAIL prevents Breast cancer-induced bone destruction in a mouse model. Cancer Research; 66 (10):5363-70.

Butler, L., Welldon, K., Hay, S., Atkins, GJ., Bouralexis, S., Findlay, D.M. and Evdokiou, A., (2006) The Histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) selectively induces expression of Death receptor 5 (DR5) and augments Apo2L/TRAIL-induced apoptosis of breast cancer cells International Journal of Cancer; 119 (4): 944-54

Bouralexis, S., Findlay, D.M. and Evdokiou, A. (2005). Death to the bad guys: targetting cancer via Apo2L/TRAIL. Apoptosis 10(1):35-51.

Bouralexis, S., Clayer, M., Hay, S., Findlay, D.M. and Evdokiou A. (2004). Sensitivity of fresh isolates of soft tissue sarcoma, osteosarcoma and giant cell tumour cells to Apo2L/TRAIL and doxorubicin. Int J Oncol 24(5):1263-70.