Professor Richard Christopherson
Professor G08 - Biochemistry and Microbiology Building
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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.
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.
- Henrich, S, Gez, S, Crossett, B, Mulligan, S, Christopherson, R. Fludarabine Induces Differential Expression of Proteins in Human Leukemia and Lymphoma Cells. Nucleosides, nucleotides & nucleic acids. 2008; 27:634-640 [Abstract]
- Langley, D, Shojaei, M, Chan, C, Lok, H, Mackay, J, Traut, T, Guss, J, Christopherson, R. Structure and inhibition of orotidine 5'-monophosphate decarboxylase from Plasmodium falciparum. Biochemistry. 2008; 47:3842-3854 [Abstract]
- Henrich, S, Christopherson, R. 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. 2008; 22:657-60 [Abstract]
- Barber, N, Belov, L, Christopherson, R. All-trans retinoic acid induces different immunophenotypic changes on human HL60 and NB4 myeloid leukaemias. Leukemia research. 2008; 32:315-22 [Abstract]
- Lee, M, Maher, M, Christopherson, R, Guss, J. Kinetic and Structural Analysis of Mutant Escherichia coli Dihydroorotases: A Flexible Loop Stabilizes the Transition State(,). Biochemistry. 2007; 46:10538-50 [Abstract]
- Gez, S, Crossett, B, Christopherson, R. Differentially expressed cytosolic proteins in human leukemia and lymphoma cell lines correlate with lineages and functions. Biochimica et biophysica acta. 2007; 1774:1173-83 [Abstract]
- Lee, M, Chan, C, Graham, S, Christopherson, R, Guss, J, Maher, M. Structures of Ligand-free and Inhibitor Complexes of Dihydroorotase from Escherichia coli: Implications for Loop Movement in Inhibitor Design. Journal of molecular biology. 2007; 370:812-825 [Abstract]
- Henrich, S, Cordwell, S, Crossett, B, Baker, M, Christopherson, R. The nuclear proteome and DNA-binding fraction of human Raji lymphoma cells. Biochimica et biophysica acta. 2007; 1774:413-432 [Abstract]
- Leong, S, Christopherson, R, Baxter, R. Profiling of Apoptotic Changes in Human Breast Cancer Cells Using SELDI-TOF Mass Spectrometry. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2007; 20:579-90 [Abstract]
- Henrich, S, Crossett, B, Christopherson, R. Differentially expressed nuclear proteins in human CCRF-CEM, HL-60, MECA and Raji cells correlate with cellular properties. PROTEOMICS CLINICAL APPLICATIONS. 2007; 1:1252-1265 [Abstract]
- Belov, L, Mulligan, S, Barber, N, Woolfson, A, Scott, M, Stoner, K, Chrisp, J, Sewell, W, Bradstock, K, Bendall, L, Pascovici, D, Thomas, M, Erber, W, Huang, P, Sartor, M, Young, G, Wiley, J, Juneja, S, Wierda, W, Green, A, Keating, M, Christopherson, R. Analysis of human leukaemias and lymphomas using extensive immunophenotypes from an antibody microarray. British journal of haematology. 2006; 135:184-97 [Abstract]
- Huang, D, Kaplan, J, Menz, R, Katis, V, Wake, R, Zhao, F, Wolfenden, R, Christopherson, R. Thermodynamic Analysis of Catalysis by the Dihydroorotases from Hamster and Bacillus caldolyticus, As Compared with the Uncatalyzed Reaction. Biochemistry. 2006; 45:8275-83 [Abstract]
- Woolfson, A, Ellmark, P, Chrisp, J, A Scott, M, Christopherson, R. The application of CD antigen proteomics to pharmacogenomics. Pharmacogenomics. 2006; 7:759-771 [Abstract]
- Anderson, M, Cleland, W, Huang, D, Chan, C, Shojaei, M, Christopherson, R. 13C and 15N isotope effects for conversion of L-dihydroorotate to N-carbamyl-L-aspartate using dihydroorotase from hamster and Bacillus caldolyticus. Biochemistry. 2006; 45:7132-9 [Abstract]
- Ellmark, P, Belov, L, Huang, P, Lee, C, Solomon, M, Morgan, D, Christopherson, R. Multiplex detection of surface molecules on colorectal cancers. Proteomics. 2006; 6:1791-802 [Abstract]
- Christopherson, R, Stoner, K, Barber, N, Belov, L, Woolfson, A, Scott, M, Bendall, L, Mulligan, S. Classification of AML using a monoclonal antibody microarray. Methods in molecular medicine. 2006; 125:241-51 [Abstract]
- Sluyter, R, Georgiou, J, Skarratt, K, Fuller, S, Martin, C, Christopherson, R, Wiley, J. Human epidermal and monocyte-derived langerhans cells express functional P2X7 receptors. Tissue Antigens. 2005; 66:546-546 [Abstract]
- Belov, L, Huang, P, Chrisp, J, Mulligan, S, Christopherson, R. Screening microarrays of novel monoclonal antibodies for binding to T-, B- and myeloid leukaemia cells. Journal of immunological methods. 2005; 305:10-9 [Abstract]
- White, S, Belov, L, Barber, N, Hodgkin, P, Christopherson, R. Immunophenotypic changes induced on human HL60 leukaemia cells by 1alpha,25-dihydroxyvitamin D3 and 12-O-tetradecanoyl phorbol-13-acetate. Leukemia research. 2005; 29:1141-51 [Abstract]
- Georgiou, J, Skarratt, K, Fuller, S, Martin, C, Christopherson, R, Wiley, J, Sluyter, R. Human epidermal and monocyte-derived langerhans cells express functional P2X receptors. The Journal of investigative dermatology. 2005; 125:482-90 [Abstract]
- Woolfson, A, Stebbing, J, Tom, B, Stoner, K, Gilks, W, Kreil, D, Mulligan, S, Belov, L, Chrisp, J, Errington, W, Wildfire, A, Erber, W, Bower, M, Gazzard, B, Christopherson, R, Scott, M. Conservation of unique cell-surface CD antigen mosaics in HIV-1-infected individuals. Blood. 2005; 106:1003-7 [Abstract]
- Lee, M, Chan, C, Mitchell Guss, J, Christopherson, R, Maher, M. Dihydroorotase from Escherichia coli: loop movement and cooperativity between subunits. Journal of molecular biology. 2005; 348:523-33 [Abstract]
- Christopherson, R. Nucleotide biosynthesis. In: Encyclopedic Reference of Genomics and Proteomics in Molecular Medicine. Germany: Springer 2005. p. (3).
Antigens, CD; Antibodies, Monoclonal; Leukemia; Protein Array Analysis; Immunophenotyping; Antimetabolites; Hemic and Lymphatic Diseases; Antineoplastic