Professor Richard Christopherson

Professor
Bosch Instittue, Sydney Medical School
Bosch Institute

G08 - Biochemistry Building
The University of Sydney
NSW 2006 Australia

T: +61 2 9351 6031
F: +61 2 9351 4726
E:
W: Related website

Research interests

Fludarabine induces proteins that regulate apoptosis in leukaemia cells

The purine analogues, cladribine and fludarabine, are effective as single agents in treating chronic lymphocytic leukaemia (CLL) and hairy cell leukaemia (HCL). The mechanisms of action of these anticancer drugs against CLL and HCL are being investigated using CD antibody (DotScan) microarrays and two-dimensional fluorescence differential gel electrophoresis (DIGE). We have found that both drugs induce significant changes in surface expression profiles on CLL cells, and in levels of several proteins involved in apoptosis.

Hsp90 inhibitors reduce oncogenic signalling proteins in leukaemia cells

Heat shock protein 90 (Hsp90) inhibitors such as 17-AAG are undergoing clinical trials for treatment of a variety of cancers. Hsp90 is a molecular chaperone that catalyzes the conformational maturation of a number of oncogenic signalling proteins with the hydrolysis of ATP. Inhibitors such as 17-AAG prevent the binding of ATP to Hsp90, resulting in the release and degradation of signalling proteins required for the growth of cancer. We have found that several Hsp90 inhibitors induce significant changes in the surface expression profiles and cellular proteomes of CLL and other leukaemias. The results obtained will provide insight on the mechanisms of action of these novel drugs.

Classification of leukaemias by cell surface profiling

DotScan antibody microarrays capture live leukaemia cells providing an extensive immunophenotype (surface expression profile or disease signature) for that leukaemia. This novel technology has been validated for classification of leukaemias by a clinical trial involving 796 patients. DotScan has also been used to identify significant changes induced in the immunophenotype of the human myeloid cell line, HL60, induced by all-trans retinoic acid (ATRA), Vitamin D and phorbol esters.

Surface profiling of colorectal cancers and detection of tumour-infiltrating lymphocytes (TILs)

DotScan has also been used to determine surface expression profiles of colorectal cancer (CRC) cells from surgically resected specimens. Using fluorescence multiplexing, expression profiles of CRC cells and tumour infiltrating lymphocytes (TILs) have been obtained from cancerous polyps. TILs may be very important in the future for cancer prognosis and for therapy that involves growing these TILs in vitro and infusing them back into the patient for immunotherapy.

Publications

2014 | 2013 | 2012 | 2011 | 2010 | 2009 | 2008

2014

   
  • Chik, J., Zhou, J., Moh, E., Christopherson, R., Clarke, S., Molloy, M., Packer, N. (2014), Comprehensive glycomics comparison between colon cancer cell cultures and tumours: Implications for biomarker studies. Journal of Proteomics. 108(C), 146-162. [Abstract]
  • Kaufman, K., Mactier, S., Armstrong, N., Mallawaaratchy, D., Byrne, S., Haydu, L., Jakrot, V., Thompson, J., Mann, G., Scolyer, R., Christopherson, R. (2014), Surface antigen profiles of leukocytes and melanoma cells in lymph node metastases are associated with survival in AJCC stage III melanoma patients. Clinical & Experimental Metastasis. 31, 407-421. [Abstract]
  • Alomari, M., Mactier, S., Kaufman, K., Best, O., Mulligan, S., Christopherson, R. (2014), Profiling the lipid raft proteome from human MEC1 chronic lymphocytic Leukemia Cells. Journal of Proteomics and Bioinformatics. 7(4), 005.

2013

   
  • Che, Y., Best, O., Zhong, L., Kaufman, K., Mactier, S., Raftery, M., Graves, L., Mulligan, S., Christopherson, R. (2013), Hsp90 inhibitor snx-7081 dysregulates proteins involved with dna repair and replication and the cell cycle in human chronic lymphocytic leukemia (cll) cells. Journal of Proteome Research. 12(4), 1710-1722. [Abstract]
  • Huang, P., Kohnke, P., Belov, L., Best, G., Mulligan, S., Christopherson, R. (2013), Profiles of surface mosaics on chronic lymphocytic leukemias distinguish stable and progressive subtypes. Journal of Pharmacy & Pharmaceutical Sciences. 16(2), 231-237. [Abstract]
  • Cooper, M., Cox, N., Zimmerman, E., Dewar, B., Duncan, J., Whittle, M., Nguyen, T., Jones, L., Ghose Roy, S., Smalley, D., Kuan, P., Richards, K., Christopherson, R., Jin, J., Frye, S., Johnson, G., Baldwin, A., Graves, L. (2013), Application of multiplexed kinase inhibitor beads to study kinome adaptations in drug-resistant leukemia. PloS One. 8(6), e66755. [Abstract]

2012

   
  • Kohnke, P., Mactier, S., Almazi, J., Crossett, B., Christopherson, R. (2012), Fludarabine and Cladribine Induce Changes in Surface Proteins on Human B-Lymphoid Cell Lines Involved with Apoptosis, Cell Survival, and Antitumor Immunity. Journal of Proteome Research. 11(9), 4436-4448. [Abstract]
  • Rahman, W., Huang, P., Belov, L., Chrisp, J., Christopherson, R., Stapelberg, P., Warner, F., George, J., Bowen, D., Strasser, S., Koorey, D., Sharland, A., McCaughan, G., Shackel, N. (2012), Analysis of human liver disease using a cluster of differentiation (CD) antibody microarray. Liver International. 32(10), 1527-1534. [Abstract]
  • Leong, S., Nunez, A., Lin, M., Crossett, B., Christopherson, R., Baxter, R. (2012), iTRAQ-Based Proteomic Profiling of Breast Cancer Cell Response to Doxorubicin and TRAIL. Journal of Proteome Research. 11(7), 3561-3572. [Abstract]
  • Huang, P., Giles Best, O., Belov, L., Mulligan, S., Christopherson, R. (2012), Surface profiles for sub-classification of chronic lymphocytic leukemia. Leukemia and Lymphoma. 53(6), 1046-1056. [Abstract]
  • Almazi, J., Mactier, S., Best, O., Crossett, B., Mulligan, S., Christopherson, R. (2012), Fludarabine nucleoside induces accumulations of p53, p63 and p73 in the nuclei of human B-lymphoid cell lines, with cytosolic and mitochondrial increases in p53. Proteomics - Clinical Applications. 6(5-6), 279-290. [Abstract]
  • Mallawaaratchy, D., Mactier, S., Kaufman, K., Blomfield, K., Christopherson, R. (2012), The phosphoinositide 3-kinase inhibitor LY294002, decreases aminoacyl-tRNA synthetases, chaperones and glycolytic enzymes in human HT-29 colorectal cancer cells. Journal of proteomics. 75(5), 1590-9. [Abstract]
  • Leong, S., McKay, M., Christopherson, R., Baxter, R. (2012), Biomarkers of breast cancer apoptosis induced by chemotherapy and TRAIL. Journal of proteome research. 11(2), 1240-50. [Abstract]
  • Best, O., Che, Y., Singh, N., Forsyth, C., Christopherson, R., Mulligan, S. (2012), The Hsp90 inhibitor SNX-7081 synergizes with and restores sensitivity to fludarabine in chronic lymphocytic leukemia cells with lesions in the TP53 pathway: a potential treatment strategy for fludarabine refractory disease. Leukemia & Lymphoma. 53(7), 1367-1375. [Abstract]

2011

   
  • Henrich, S., Mactier, S., Best, G., Mulligan, S., Crossett, B., Christopherson, R. (2011), Fludarabine nucleoside modulates nuclear "survival and death" proteins in resistant chronic lymphocytic leukemia cells. Nucleosides, Nucleotides and Nucleic Acids. 30(12), 1181-1189. [Abstract]
  • Mactier, S., Henrich, S., Che, Y., Kohnke, P., Christopherson, R. (2011), Comprehensive proteomic analysis of the effects of purine analogs on human Raji B-cell lymphoma. Journal of Proteome Research. 10(3), 1030-1042. [Abstract]
  • Zhou, J., Belov, L., Solomon, M., Chan, C., Clarke, S., Christopherson, R. (2011), Colorectal cancer cell surface protein profiling using an antibody microarray and fluorescence multiplexing. Journal of Visualized Experiments. 0(55), 3322. [Abstract]
  • Heath, E., Kaufman, K., Christopherson, R. (2011), B-RAF: A Contributor to the Melanoma Phenotype. The international journal of biochemistry & cell biology. 43(1), 29-32. [Abstract]

2010

   
  • Yang, F., Tay, K., Dong, L., Thorne, R., Jiang, C., Yang, E., Tseng, H., Liu, H., Christopherson, R., Hersey, P., Zhang, X. (2010), Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells. Cell Death and Differentiation. 17(8), 1354-1367. [Abstract]
  • Kaufman, K., Belov, L., Huang, P., Mactier, S., Scolyer, R., Mann, G., Christopherson, R. (2010), An extended antibody microarray for surface profiling metastatic melanoma. Journal of immunological methods. 358(1-2), 23-34. [Abstract]
  • Zhou, J., Belov, L., Huang, P., Shin, J., Solomon, M., Chapuis, P., Bokey, L., Chan, C., Clarke, C., Clarke, S., Christopherson, R. (2010), Surface antigen profiling of colorectal cancer using antibody microarrays with fluorescence multiplexing. Journal of Immunological Methods. 355(1-2), 40-51. [Abstract]
  • Cassano, J., Mactier, S., Mulligan, S., Belov, L., Huang, P., Christopherson, R. (2010), Cladribine and Fludarabine Nucleoside Change the Levels of CD Antigens on B-Lymphoproliferative Disorders. International Journal of Proteomics. 2010, 964251.
  • Belov, L., Zhou, J., Christopherson, R. (2010), Cell surface markers in colorectal cancer prognosis. International journal of molecular sciences. 12(1), 78-113. [Abstract]

2009

   
  • Kohnke, P., Mulligan, S., Christopherson, R. (2009), Membrane proteomics for leukemia classification and drug target identification. Current Opinion in Molecular Therapeutics. 11(6), 603-610. [Abstract]
  • Barber, N., Gez, S., Belov, L., Mulligan, S., Woolfson, A., Christopherson, R. (2009), Profiling CD antigens on leukaemias with an antibody microarray. FEBS Letters. , 1785-1791. [Abstract]
  • Langley, D., Shojaei, M., Chan, C., Lok, H., Mackay, J., Traut, T., Guss, J., Christopherson, R. (2009), Structure and Inhibition of Orotidine 5'-Monophosphate Decarboxylase from Plasmodium falciparum. Biochemistry. 48(11), 2570. [Abstract]

2008

   
  • Ellmark, P., Högerkorp, C., Ek, S., Belov, L., Berglund, M., Rosenquist, R., Christopherson, R., Borrebaeck, C. (2008), Phenotypic protein profiling of different B cell sub-populations using antibody CD-microarrays. Cancer Letters. 265(1), 98-106. [Abstract]
  • Henrich, S., Gez, S., Crossett, B., Mulligan, S., Christopherson, R. (2008), Fludarabine Induces Differential Expression of Proteins in Human Leukemia and Lymphoma Cells. Nucleosides, Nucleotides & Nucleic Acids. 27(6), 634-640. [Abstract]
  • Langley, D., Shojaei, M., Chan, C., Lok, H., Mackay, J., Traut, T., Guss, J., Christopherson, R. (2008), Structure and inhibition of orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum. Biochemistry. 47(12), 3842-3854. [Abstract]
  • Henrich, S., Christopherson, R. (2008), Multiple forms of nuclear p53 formed in human Raji and MEC1 cells treated with fludarabine. Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 22(0), 657-60. [Abstract]
  • Barber, N., Belov, L., Christopherson, R. (2008), All-trans retinoic acid induces different immunophenotypic changes on human HL60 and NB4 myeloid leukaemias. Leukemia research. 32(0), 315-22. [Abstract]
  • Ellmark, P., Woolfson, A., Belov, L., Christopherson, R. (2008), The applicability of a cluster of differentiation monoclonal antibody microarray to the diagnosis of human disease. Methods in Molecular Biology. 439, 199-209. [Abstract]