Research units - Pharmacogenomics

Pharmacogenomics

Pharmacogenomics is the study of how an individual’s genetic makeup affects the course of disease and responses to medication. Work at SVI combines traditional sciences, such as biochemistry, with recent advances in our knowledge of genetics and drug discovery. This allows us to identify genes that are involved in disease and help design drugs to stop them from working. We have recently identified genes involved in the spread of cancer and those associated with the onset of diabetic kidney damage.

Research Overview

It is with some certainty that over the next 20 years we will see huge advances in the area of personalized therapies for disease. This will come about due to the improved ability to detect and interpret specific molecular attributes of an individuals' disease condition. Along these lines, the laboratories main area of interest is pharmacogenomics, a discipline which incorporates bioinformatic approaches to the cataloguing and processing of information relating to pharmacology and genetics. It is applied to identify drug targets, examining the 'molecular patterns' found in patients' samples, and to the study of how genes affect a person's response to drugs. Principle disease interests of the Pharmacogenomics Lab are cancer and diabetes. We have four main project areas: (1) Anti-cancer and anti-metastasis drug development, (2) Genomic profiling of the epithelial-to-mesenchymal transition in cancer metastasis, (3) Gene expression changes associated with diabetic complications, and (4) Cancer bioinformatics.

Research Themes

Anti-cancer and anti-metastasis drug development

Genomic profiling of the epithelial-to-mesenchymal transition in cancer metastasis

Gene expression changes associated with diabetic complications

Cancer bioinformatics

Honours and PhD Projects

Identification of bone metastasis genes in a xenograft model of experimental breast cancer

Epithelial-to-mesenchymal transition in human breast cancer

Pharmacogenomics

Galectin-3 and breast cancer metastasis

Staff

Staff image

Dr Mark Waltham
Annabel Southy
Mina Rizk
Sam Rudstein
Timothy Tan
Dr Walter Pfister

Publication Highlights

  1. Gorlick, R., Goker, E., Trippett, T., Waltham, M., Banerjee, D. and Bertino, J.R. Mechanisms of intrinsic and acquired resistance to methotrexate in acute leukemia. New Eng. J. Med. (1996) 335: 1041-1048.
  2. Waltham, M., Li, W-W., Gritsman, H., Tong, W.P. and Bertino, J.R. g-Glutamyl hydrolase from human sarcoma 1080 cells: Characterization and inhibition by glutamine antagonists. Molecular Pharmacology (1997) 51: 825-832.
  3. Weinstein, J.N., Waltham, M., Reinhold, W., Lee, J.K., Smith, L.H., Andrews, D., Tanabe, L., Zhou, Y., Myers, T.G., Buolamwini, J.K., and Scherf, U. The current revolution in cancer drug discovery: Genomics, proteomics, and bioinformatics. pg 21-36 in Fighting against Cancer: Progress and New Hopes, 2000.
  4. Scherf, U., Ross, D.T., Waltham, M., Smith, L.H., Lee, J.L., Kohn, K.W.,Myers, T.G., Eisen, M.B., Reinhold, W.C., Andrews, D.T., Scudiero, D.A., Pommier, Y., Botstein, D., Brown, P.O. and Weinstein, J.N. A cDNA microarray gene expression database for the molecular pharmacology of cancer: gene-drug correlations. Nature Genetics (2000) 24(3): 227-234.
  5. Ross, D.T, Scherf, U., Eisen, M.B., Perou, C.M., Spellman, P., Iyer, V., Jeffrey, S.S., Van de Rijn, M., Waltham, M., Pergamenschikov, A., Lee, J.C.F., Lashkari, D., Shalon, D., Myers, T.G., Weinstein, J.N., Botstein, D. and Brown, P.O. Exploring the phenotypes encoded in the gene expression patterns in sixty tumor derived cell lines. Nature Genetics (2000) 24(3): 236-244.
  6. 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. Proteomic profiling of the NCI60 cancer cell lines using new high-density 'reverse-phase' lysate microarrays. P. Natl. Acad. Sci. USA, (2003) Vol. 100 (24): 14229-14234.
  7. Tester, A. M., 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. Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice. Cancer Research, (2004) Vol. 64 (2), 652-658.
  8. Kamarinos, M. and M. Waltham, Microarrays in medical research. Australian Biochemist, (2004), Vol. 35(2): 36-39.