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Dr Mark Waltham
St. Vincent's Institute of Medical Research and Department of Surgery,
University of Melbourne
Melbourne, Vic 3065
Email: waltham@medstv.unimelb.edu.au
Tel: +61-7-9288-2566
Fax: +61-7-9416-2676
Homepage: http://www.svimr.unimelb.edu.au/waltham.htm

Research
Our laboratory is interested in defining the molecular processes associated with disease progression and the concept of tailoring patient-specific therapies. Progress toward achieving these goals has been greatly assisted by recent advances in technologies that permit en masse evaluation of gene and protein expression levels: namely microarray profiling and proteomics. Most of our projects are cancer related. With respect to protease biology, one project performed in collaboration with A/Prof Erik Thompson has entailed microarray expression profiling a breast cancer model of induced invasion and metastasis. MMP-2 levels where significantly induced within 24hr, though a novel, and perhaps more interesting find that the gene TFPI2 (tissue factor pathway inhibitor-2) was dramatically (& transiently) upregulated within several hrs. The TFPI2 protein has been implicated in both pro- and anti-invasive pathways by virtue of its serine proteinase inhibition and we are currently assessing the potential of this activity to drive some of the processes associated with tumour invasion. Using mouse xenograft models of tumour progression and metastasis, we are also profiling the pharmacological response to a number of novel anticancer agents, including MMP inhibitors. In a separate recently initiated diabetes project, we have identified a significant down regulation of an individual MMP in primary mesangial and kidney proximal tubule cells maintained under conditions of high glucose. Reduced expression of this MMP coincides with increased extracellular matrix deposition and this finding has subsequently been confirmed in a number of animal model systems of diabetic nephropathy. We now intend to expression profile levels of all (known) MMPs in accrued kidney biopsy samples from patients with this disease.
Collaborations
A/Prof Erik Thompson
Prof Richard Gilbert
Prof Carol Pollok
Dr John Price
Prof Zena Werb
Dr David Shalinsky
A/Prof Tracey Brown.
Publications
ProMMP-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice. Tester, A., Waltham, M., Oh, S-J., Bae, S.N., Bills, M.M., Walker, E.C., Kern, F.G., Stetler-Stevenson, W.G., Lippman, M.E., and E. W. Thompson. Cancer Research, Jan 15th, 2004 issue.

Proteomic profiling of the NCI60 cancer cell lines using new high-density reverse-phase lysate microarrays. Nishizuka, S., Charboneau, L., Young, L., Major, S., Reinhold, W.C., Waltham, M., Kouros-Mehr, H., Bussey, K.J., Lee, J.K., Munson, P.J., Petricoin, E., I, Liotta, L.A., and J. N. Weinstein. PNAS (2003) 100(24): 14229-14234.

Diagnostic markers that distinguish colon and ovarian adenocarcinomas: Identification by genomic, proteomic, and tissue array profiling. Nishizuka, S., Chen, S-T., Gwadry, F.G., Alexander, J., Major, S.M., Scherf, U., Reinhold, W.C., Waltham, M., Charboneau, L., Young, L., Bussey, K.J., Kim, S., Lababidi, S., Lee, J.K., Pittaluga, S., Scudiero, D.S., Sausville, E.A., Munson, P.J., Petricoin, E.F., Liotta, L.A., Hewitt, S.M., Raffeld, M. and J.N. Weinstein Cancer Research (2003) 63: 5243-5250.





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