Dr. Claudine Bonder

Address	Rm 3-205-H Division of Human Immunology Hanson Institute, IMVS, Frome Road, Adelaide SA 5000, Australia
Phone	+61 8 8222 3504
Fax	+61 8 8232 4092
Email	Claudine.Bonder@imvs.sa.gov.au
	Research Interests

Affiliations:

Associate Member, Hanson Institute
Affiliate Senior Lecturer, Department of Medicine, University of Adelaide

Qualifications: B.Sc. (Hons), PhD.


Experience:

Selected Awards:

Invited Referee for Journals:

Lab Members

Research Interests

The primary focus of my research is driven by my desire to alleviate the pain and suffering of inflammation and auto-immune diseases. My training in immunology and cellular biology, as described below, allow me to specifically work on the development of blood vessels and the trafficking of leukocytes to sites of inflammation with the belief that a better understanding of this process is needed to design clinical trials with greater possibility of success. 

My PhD at Flinders University with Dr Prue Hart focussed on the involvement of cytokines and their receptors in autoimmune diseases. In brief, I demonstrated that a novel receptor complex for the anti-inflammatory cytokine interleukin (IL)-4 exists and suggested that this alteration in cytokine receptor formation may be key to the inflammation required for the development of rheumatoid arthritis.

Following my PhD I spent the 3 years with Prof. Paul Kubes at the University of Calgary in Alberta, Canada. Prof. Kubes is a world leader in investigating the recruitment of leukocytes to inflammatory sites in vivo as he specializes in intravital microscopy of brain, liver, skin, intestine and muscle to visualize and quantify leukocyte trafficking in vivo. During my training with Prof. Kubes I expanded on my research portfolio, to study the role of adhesion molecules (selectins and integrins) which regulate the recruitment of different leukocytes (e.g. neutrophils and T lymphocytes) into murine models of inflammation (see Figure 1). More specifically, I have worked on projects which investigate the role of inflammatory cytokines (e.g. IL-4 and TNFa) as well as different adhesion molecules (e.g. P-selectin, E-selectin, a4-integrin and CD18) in inflammatory bowel disease and hepatitis. 

 
Figure 1

In 2005 I returned to Australia to work with Prof. Jennifer Gamble in the Vascular Biology Laboratory, Division of Human Immunology, Hanson Institute, IMVS. With Prof. Gamble the focus of my study has been to better understand the development of blood vessels i.e. angiogenesis in normal and disease states using both in vivo and in vitro systems. In brief, I have shown that a lipid enzyme, sphingosine kinase, regulates endothelial progenitor cell maturation as well as survival signals of endothelial cells during starvation (see Figure 2).

Figure 2

SK-1 is well described in EC, by us and others, to mediate cell survival, proliferation and migration. In EC, SK has a certain level of intrinsic activity which is said to promote proliferation and survival and that more than one physiological stimuli can increase SK-1 activity such that it translocates from the cytoplasm to plasma membrane in order to catalyze its substrate, sph, to form S1P. This S1P can be secreted and is known to act on a family of GPCRs at cell surface to induce survival, angiogenesis and motility.

In 2007 I received an NHMRC Project Grant and now head the new Vascular Biology and Cell Trafficking Laboratory with a primary focus to understand the physiology of vasculogenesis and leukocyte recruitment in normal and disease states. I use currently available molecular tools to bring together all my training to assess the importance of inflammatory mediators, adhesion molecules and associated proteins including mutant mice missing the gene(s) for certain proteins involved in the recruitment cascade (eg sphingosine kinase) with cancer and rheumatoid arthritis as key areas (see Figure 3). In the near future I will complement my in vitro human and murine work with in vivo studies to better understand these processes.   

Figure 3

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Selected Publications

• Kerfoot S.M., Andonegui G., Bonder C.S. and Liu L.
  Exogenous stromal cell-derived factor-1 induces modest leukocyte recruitment in vivo.
  Am. J. Physiology (Heart and Circulatory Physiology); accepted April 10th 2008.

• Li X., Stankovic M., Bonder C., Hahn C., Parsons M., Pitson S., Xia P., Prioa R., Vadas M. and Gamble J. Basal and angiopoetin-1-mediated endothelial permeability is regulated by sphingosine kinase-1.
  Blood, 111(7): 3489-97, 2008.

• Pebay A., Bonder C.S. and Pitson S.
  Stem cell regulation by lysophospholipids.
  Prostaglandins and other Lipid Mediators, 84: 83-97, 2007

• Kerfoot S.M., Norman M.U., Lapointe B.M., Bonder C.S., Zbytnuik L. and Kubes P.
  Re-evaluation of P-selectin and a4-integrin as targets for the treatment of experimental autoimmune encephalomyelitis.
  Journal of Immunology. 176(10): 6225-34, 2006.

• Bonder C.S., Clark S.R., Norman M.U., Johnson P. and Kubes P.
  Use by CD44 to regulate CD4+ Th1 and Th2 lymphocytes to roll and adhere.
  Blood. 107(12): 4798-806,2006.

• Bonder C.S., Norman M.U., Macrae T., Mangan P.R., Bullard D., Weaver C.T., McCafferty D.M. and Kubes P.
  P-selectin: the principle mediator for Th1 and Th2 lymphocyte trafficking in the intestine. 
  Am. J. Pathol.167(6):1647-60, 2005.

• Bonder C.S., Norman M.U., Swain M.G. Zbytnuik L.D., Yamanouchi J., Santamaria P., Ajuebor M., Salmi M., Jalkanen S. and Kubes P.
  Rules of recruitment for Th1 and Th2 lymphocytes in inflamed liver: A role for alpha-4 integrin and vascular adhesion protein-1 (VAP-1).
  Immunity. 23(2):153-63, 2005.

• Zanardo R.C.O., Bonder C.S., Hwang J.M., Andonegui G., Liu L., Vestweber D., Zbytnuik L.D. and Kubes P.
  A down-regulatory E-selectin ligand is functionally important for PSGL-1-independent leukocyte endothelial interactions.
  Blood, 104(12):3766-73, 2004.

• Bonder C.S., Knight D., Hernandez-Saavedra D., McCord J.M. and Kubes P.
  Chimeric SOD2/3 inhibits at the endothelial-neutrophil interface to limit vascular dysfunction in ischemia-reperfusion
  Am. J. Physiol (GI and Liver) 287(3):G676-84, 2004.

• Bonder C.S., Ajuebor M.N., Zbytnuik L.D., Kubes P. and Swain M.G.
  Essential role for neutrophil recruitment to the liver in Concanavalin A-induced hepatitis
  J Immunol.  172; 45-53, 2004.

• *Andonegui G., *Bonder C.S., Green F., Mullaly S.C., Zbytnuik L., Raharjo E. and Kubes P. Endothelium-derived Toll-like receptor-4 is the key molecule in LPS-induced neutrophil sequestration into lungs.
  J Clin Invest. 111(7); 1011-20, 2003. * authors contributed equally to this work

• Bonder C.S., Davies K.V.L., Xiang L., Hertzog P.J., Woodcock J.M., Finlay-Jones J.J. and Hart P.H.
  Endogenous interferon-a reduces gc expression and blocks IL-4 regulation of TNFa production by human monocyte-derived macrophages
  Cytokine, 17; 187-96, 2002.

• Bonder C.S., Davies K.V.L., Hosszu E.K., Finlay-Jones J.J. and Hart P.H.
  Interferon-g down-regulates IL-4 functional activity on monocytes by multiple mechanisms.
  Journal of Interferon and Cytokine Research, 22; 287-293, 2002.

• Bonder C.S., Hart P.H., Davies K.V.L., Burkly L.C., Finlay-Jones J.J. and Woodcock J.M.
  Characterization of IL-4 receptor components expressed on monocytes and monocyte-derived macrophages: variation associated with differential signalling by IL-4.
  Growth Factors, 19; 207-18, 2001.

• Bonder C.S., Finlay-Jones J.J. and Hart P.H.
  Interleukin-4 regulation of human monocyte and macrophage interleukin-10 and interleukin-12 production. Role of a functional interleukin-2 receptor g chain.
  Immunology 96; 529-536, 1999.

• Hart P.H., Bonder C.S., Balogh J., Dickensheets H.L., Vazquez N., Davies K.V.L., Finlay-Jones J.J. and Donnelly R.P.
  Diminished responses to IL-13 by human monocytes differentiated in vitro. Role of the IL-13Ra1 chain and STAT6.
  Eur. J. Immunol. 29; 2087-2097, 1999.

• Bonder C.S., Dickensheets H.L., Finlay-Jones J.J., Donnelly R.J. and Hart P.H.
  The involvement of the IL-2 receptor g chain (gc) in the control by IL-4 of monocyte and macrophage pro-inflammatory mediator production.
  J. Immunol., 160; 4048-4056, 1998.

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Collaborations

‘Novel anti-inflammatory compounds for rheumatoid arthritis’
Prof. Tony Ferrante and Dr Nick Gorgani,
Department of Immunopathology
Children, Youth and Women's Health Services, Adelaide, SA

Funding

National Health and Medical Research Council	Arthritis Australia
Royal Adelaide Hospital & the Institute of Medical and Veterinary Science. Mary Overton Award 2007 ($50,000)

Available Student Projects

• Regulatory T lymphocytes and antibody production in arthritis: a role for the enzyme sphingosine kinase (see attached PDF )
• Control of vascular development: a role for the enzyme sphingosine kinase (see attached PDF )
• Tumour development: a role for the enzyme sphingosine kinase (see attached PDF )

Comittee Member

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