Assoc Prof Terry Johns - Researcher Profile

Biography

After completing a PhD in 1993 at Monash University, where he worked on interferon and melanoma, A/Prof. Johns joined Prof. Claude Bernard’s multiple sclerosis group.  During his time there, he developed a new animal model of multiple sclerosis that remains the gold standard today.

In 1998, A/Prof. Johns commenced at the Ludwig Institute in Melbourne and went on to establish the Oncogenic Signalling Laboratory.  The main focus of the laboratory was the development of antibodies that target receptors important to the survival and growth of cancer.   Of particular note was the development of mAb 806, a cancer-specific antibody directed to the EGFR that has been licensed to Abbot. 

A/Prof. Johns joined Monash University in March 2008, moving his laboratory with him.  He continues to develop novel therapeutic antibodies designed to treat cancer.  He has an emphasis on glioma and receptor tyrosine kinase networks. 

 

Keywords

Brain Cancer, Glioma, Antibody Therapy, Receptor tyrosine kinases

Qualifications

DOCTOR OF PHILOSOPHY

Institution: Monash University

Year awarded: 1993

BACHELOR OF SCIENCE (HONOURS)

Institution: Monash University

Year awarded: 1985

Publications

Book Chapters

Johns, T.G., 2012, Advances in the development of EGFR targeted therapies for the treatment of glioblastoma, in Novel Therapeutic concepts in targeting glioma, eds Faris Farassati, InTech, Shanghai, China, pp. 27-42.

Journal Articles

Koziolek, E.J., Donoghue, J.F., Bentley, J.D., Lovrecz, G.O., Dolezal, O., Ward, C.W., Rothacker, J., Nice, E., Burgess, A.W., Hafner, M., Johns, T.G., Adams, T.E., 2012, A high-affinity ErbB4Fc fusion protein is a potent antagonist of heregulin-mediated receptor activation, Growth Factors [P], vol 30, issue 5, Informa Healthcare, United Kingdom, pp. 310-319.

Weickhardt, A.J., Price, T.J., Chong, G., Gebski, V., Pavlakis, N., Johns, T.G., Azad, A., Skrinos, E., Fluck, K., Dobrovic, A., Salemi, R., Scott, A.M., Mariadason, J.M., Tebbutt, N.C., 2012, Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer, Journal of Clinical Oncology [P], vol 30, issue 13, American Society of Clinical Oncology, United States, pp. 1505-1512.

Greenall, S., Gherardi, E., Liu, Z., Donoghue, J.F., Vitali, A.A., Li, Q., Murphy, R., Iamele, L., Scott, A.M., Johns, T.G., 2012, Non-agonistic bivalent antibodies that promote c-MET degradation and inhibit tumor growth and others specific for tumor related c-MET, PLoS ONE [P], vol 7, issue 4 (Art. No: e34658), Public Library of Science, United States, pp. 1-10.

Feng, H., Hu, B., Jarzynka, M.J., Li, Y., Keezer, S., Johns, T.G., Tang, C.K., Hamilton, R.L., Vuori, K., Nishikawa, R., Sarkaria, J.N., Fenton, T., Cheng, T., Furnari, F.B., Cavenee, W.K., Cheng, S., 2012, Phosphorylation of dedicator of cytokinesis 1 (Dock180) at tyrosine residue Y722 by Src family kinases mediates EGFRvIII-driven glioblastoma tumorigenesis, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 109, issue 8, National Academy of Science, United States, pp. 3018-3023.

Donoghue, J., Bogler, O., Johns, T., 2011, A simple guide screw method for intracranial xenograft studies in mice, Journal of Visualized Experiments [E], vol 55, issue e3157, Journal of Visualized Experiments, United States, pp. 1-5.

Cvrljevic, A., Akhavan, D., Wu, M., Martinello, P., Furnari, F., Johnston, A., Guo, D., Pike, L., Cavenee, W., Scott, A., Mischel, P., Hoogenraad, N., Johns, T., 2011, Activation of Src induces mitochondrial localisation of de2-7EGFR (EGFRvIII) in glioma cells: Implications for glucose metabolism, Journal Of Cell Science [P], vol 124, issue Pt 17, The Company of Biologists Ltd, United Kingdom, pp. 2938-2950.

Ymer, S., Greenall, S., Cvrljevic, A., Cao, D., Donoghue, J., Epa, V., Scott, A., Adams, T., Johns, T., 2011, Glioma specific extracellular missense mutations in the first cysteine rich region of Epidermal Growth Factor Receptor (EGFR) initiate ligand independent activation, Cancers [E], vol 3, issue 2, M D P I AG, Switzerland, pp. 2032-2049.

Lee, F., O'Keefe, G.J., Gan, H.K., Mountain, A.J., Jones, G.R., Saunder, T.H., Sagona, J., Rigopoulos, A., Smyth, F.E., Johns, T.G., Govindan, S.V., Goldenberg, D.M., Old, L.J., Scott, A.M., 2010, Immuno-PET quantitation of de2-7 epidermal growth factor receptor expression in glioma using 124I-IMP-R4-labeled antibody ch806, Journal of Nuclear Medicine [P], vol 51, issue 6, Society of Nuclear Medicine, United States, pp. 967-972.

Johns, T.G., McKay, M.J., Cvrljevic, A.N., Gan, H.K., Taylor, C., Xu, H., Smyth, F.E., Scott, A.M., 2010, MAb 806 enhances the efficacy of ionizing radiation in glioma xenografts expressing the de2-7 epidermal growth factor receptor, International Journal of Radiation Oncology Biology Physics [P], vol 78, issue 2, Elsevier Inc., United States, pp. 572-578.

Inda, M., Bonavia, R., Mukasa, A., Narita, Y., Sah, D.W., Vandenberg, S., Brennan, C., Johns, T.G., Bachoo, R., Hadwiger, P., Tan, P., DePinho, R.A., Cavenee, W.K., Furnari, F.B., 2010, Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma, Genes & Development [P], vol 24, issue 16, Cold Spring Harbor Laboratory Press, USA, UK, pp. 1731-1745.

Adams, T.E., Koziolek, E.J., Hoyne, P.H., Bentley, J.D., Lu, L., Lovrecz, G.O., Ward, C.W., Lee, F.T., Scott, A.M., Nash, A., Rothacker, J., Nice, E., Burgess, A., Johns, T.G., 2009, A truncated soluble epidermal growth factor receptor-Fc fusion ligand trap displays anti-tumour activity in vivo, Growth Factors [P], vol 27, issue 3, Informa Healthcare, UK, pp. 141-154.

Garrett, T.P., Burgess, A.W., Gan, H.K., Luwor, R.B., Cartwright, G.A., Walker, F., Orchard, S.G., Clayton, A.H.A., Nice, E.C., Rothacker, J., Catimel, B., Cavenee, W.K., Old, L.J., Stockert, E., Ritter, G., Adams, T.E., Hoyne, P.A., Wittrup, K.D., Chao, G., Cochran, J.R., Luo, C.S., Lou, M., Huyton, T., Xu, Y., Fairlie, W.D., Yao, S., Scott, A.M., Johns, T.G., 2009, Antibodies specifically targeting a locally misfolded region of tumor associated EGFR, Proceedings Of The National Academy Of Sciences O..., vol 106, issue 13, National Academy of Sciences, United States, pp. 5082-5087.

Lu, K.V., Zhu, S., Cvrljevic, A.N., Huang, T.T., Sarkaria, S., Ahkavan, D., Dang, J., Dinca, E.B., Plaisier, S.B., Oderberg, I., Lee, Y., Chen, Z., Caldwell, J.S., Xie, Y., Loo, J.A., Seligson, D., Chakravari, A., Lee, F.Y., Weinmann, R., Cloughesy, T.F., Nelson, S.F., Bergers, G., Graeber, T., Furnari, F.B., James, C.D., Cavenee, W.K., Johns, T.G., Mischel, P.S., 2009, Fyn and SRC are effectors of oncogenic epidermal growth factor receptor signaling in glioblastoma patients, Cancer Research [P], vol 69, issue 17, American Association for Cancer Research, USA, pp. 6889-6898.

Gan, H.K., Lappas, M., Cao, D.X., Cvrljevic, A.N., Scott, A.M., Johns, T.G., 2009, Targeting a unique EGFR epitope with monoclonal antibody 806 activates NF-kappaB and initiates tumour vascular normalization, Journal Of Cellular And Molecular Medicine [P], vol 13, issue 9B, Wiley-Blackwell Publishing Ltd, UK, pp. 3993-4001.

Pillay, V., Allaf, L., Wilding, A., Donoghue, J.F., Court, N.W., Greenall, S.A., Scott, A.M., Johns, T.G., 2009, The plasticity of oncogene addiction: Implications for targeted therapies directed to receptor tyrosine kinases, Neoplasia [P], vol 11, issue 5, Neoplasia Press, United States, pp. 448-458.

Zhang, H., Sunnarborg, S.W., McNaughton, K.K., Johns, T.G., Lee, D.C., Faber, J.E., 2008, Heparin-binding epidermal growth factor-like growth factor signaling in flow-induced arterial remodeling, Circulation Research, vol 102, issue 10, Lippincott Williams & Wilkins, USA, pp. 1275-1285.

Ashley, D., Riffkin, C.D., Lovric, M.M., Mikeska, T., Dobrovic, A., Maxwell, J.A., Friedman, H.S., Drummond, K.J., Kaye, A.H., Gan, H.K., Johns, T.G., Hawkins, C.J., 2008, In vitro sensitivity testing of minimally passaged and uncultured gliomas with TRAIL and/or chemotherapy drugs, British Journal of Cancer, vol 99, issue 2, Nature Publishing Group, UK, pp. 294-304.

Scott, A.M., Lee, F., Tebbutt, N., Herbertson, R., Gill, S.S., Liu, Z., Skrinos, E., Murone, C., Saunder, T., Chappell, B., Papenfuss, A.T., Poon, A.M.T., Hopkins, W., Smyth, F.E., MacGregor, D., Cher, L.M., Jungbluth, A.A., Ritter, G., Brechbiel, M., Murphy, R., Burgess, A.W., Hoffman, E.W., Johns, T.G., Old, L.J., 2007, A phase I clinical trial with monoclonal antibody ch806 targeting transitional state and mutant epidermal growth factor receptors, Proceedings of the National Academy of Sciences of the United States of America, vol 104, issue 10, National Academy of Sciences, USA, pp. 4071-4076.

Perera, R.M., Zoncu, R., Johns, T.G., Pypaert, M., Lee, F., Mellman, I., Old, L.J., Toomre, D.K., Scott, A.M., 2007, Internalization, intracellular trafficking, and biodistribution of monoclonal antibody 806: a novel anti-epidermal growth factor receptor antibody, NeoPlasia, vol 9, issue 12, Neoplasia Press, USA, pp. 1099-1110.

Johns, T.G., Perera, R.M., Vernes, S.C., Vitali, A.A., Cao, D.X., Cavenee, W.K., Scott, A.M., Furnari, F.B., 2007, The efficacy of epidermal growth factor receptor-specific antibodies against glioma xenografts is influenced by receptor levels, activation status, and heterodimerization, Clinical Cancer Research, vol 13, issue 6, American Association for Cancer Research (A AC R), USA, pp. 1911-1925.

Gan, H.K., Walker, F., Burgess, A.W., Rigopoulos, A., Scott, A.M., Johns, T.G., 2007, The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 increases the formation of inactive untethered EGFR dimers: Implications for combination therapy with monoclonal antibody 806, Journal of Biological Chemistry, vol 282, issue 5, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 2840-2850.

Clayton, A.H.A., Tavarnesi, M.L., Johns, T.G., 2007, Unligated epidermal growth factor receptor forms higher order oligomers within microclusters on A431 cells that are sensitive to tyrosine kinase inhibitor binding, Biochemistry, vol 46, issue 15, American Chemical Society, USA, pp. 4589-4597.

Wade, J.D., Hojo, K., Kawasaki, K., Johns, T.G., Catimel, B., Rothacker, J., Nice, E.C., 2006, An automated peptide and protein thiazolidine coupling chemistry for biosensor immobilization giving a unique N-terminal orientation, Analytical Biochemistry, vol 348, issue 2, Academic Press Inc Elsevier Science, USA, pp. 315-317.

Liu, B., Chen, H., Johns, T.G., Neufeld, A.H., 2006, Epidermal growth factor receptor activation: An upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury, Journal of Neuroscience, vol 26, issue 28, Society for Neuroscience, USA, pp. 7532-7540.

Ellis, A.G., Doherty, M.M., Walker, F., Weinstock, J., Nerrie, M., Vitali, A., Murphy, R., Johns, T.G., Scott, A.M., Levitski, A., McLachlan, G., Webster, L.K., Burgess, A.W., Nice, E., 2006, Preclinical analysis of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGF receptor tyrosine kinase, Biochemical Pharmacology, vol 71, Elsevier, USA, pp. 1422-1434.

Panousis, C., Rayzman, V.M., Johns, T.G., Renner, C., Liu, Z., Cartwright, G.A., Lee, F., Wang, D., Gan, H.K., Cao, D., Kypridis, A., Smyth, F.E., Brechbiel, M.W., Burgess, A.W., Old, L.J., Scott, A.M., 2005, Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR, British Journal of Cancer, vol 92, issue 6, Nature Publishing Group, UK, pp. 1069-1077.

Lee, F., Mountain, A.J., Kelly, M.P., Hall, C., Rigopoulos, A., Johns, T.G., Smyth, F.E., Brechbiel, M.W., Nice, E.C., Burgess, A.W., Scott, A.M., 2005, Enhanced efficacy of radioimmunotherapy with90Y-CHX-A"- DTPA-hu3S193 by inhibition of epidermal growth factor receptor (EGFR) signaling with EGFR tyrosine kinase inhibitor AG1478, Clinical Cancer Research, vol 11, issue 19 (Pt 2), American Association for Cancer Research (A AC R), Philadelphia PA USA, pp. s7080-s7086.

Whitson, K.B., Whitson, S.R., Red-Brewer, M.L., McCoy, A.J., Vitali, A.A., Walker, F., Johns, T.G., Beth, A.H., Staros, J.V., 2005, Functional effects of glycosylation at Asn-579 of the epidermal growth factor receptor, Biochemistry, vol 44, issue 45, American Chemical Society, USA, pp. 14920-14931.

Scott, A.M., Liu, Z., Murone, C., Johns, T.G., Macgregor, D., Smyth, F.E., Lee, F., Cebon, J., Davis, I.D., Hopkins, W., Mountain, A.J., Rigopoulos, A., Hanai, N., Old, L.J., 2005, Immunological effects of chimeric anti-GD3 monoclonal antibody KM871 in patients with metastatic melanoma, Cancer Immunity, vol 5, Academy of Cancer Immunology, Switzerland, pp. 3-14.

Johns, T.G., Mellman, I., Cartwright, G.A., Ritter, G., Old, L.J., Burgess, A.W., Scott, A.M., 2005, The antitumor monoclonal antibody 806 recognizes a high-mannose form of the EGF receptor that reaches the cell surface when cells over-express the receptor, The Faseb Journal, vol 19, issue 7, Federation of American Societies for Experimental Biology, USA, pp. 780-782.

Perera, R.M., Narita, Y., Furnari, F.B., Gan, H.K., Murone, C., Ahlkvist, M., Luwor, R.B., Burgess, A.W., Stockert, E., Jungbluth, A.A., Old, L.J., Cavenee, W.K., Scott, A.M., Johns, T.G., 2005, Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity, Clinical Cancer Research, vol 11, issue 17, American Association for Cancer Research (A AC R), USA, pp. 6390-6399.

Walker, F., Orchard, S.G., Jorissen, R.N., Hall, N.E., Zhang, H., Hoyne, P.A., Adams, T.E., Johns, T.G., Ward, C.W., Garrett, T.P.J., Zhu, H., Nerrie, M., Scott, A.M., Nice, E.C., Burgess, A.W., 2004, CR1/CR2 interactions modulate the functions of the cell surface epidermal growth factor receptor, Journal of Biological Chemistry, vol 279, issue 21, American Society for Biochemistry and Molecular Biology, Inc., USA, pp. 22387-22398.

Johns, T.G., Adams, T.E., Cochrane, J.R., Hall, N.E., Hoyne, P.A., Olsen, M.J., Kim, Y., Rothacker, J., Nice, E.C., Walker, F., Ritter, G., Jungbluth, A.A., Old, L.J., Ward, C.W., Burgess, A.W., Wittrup, K.D., Scott, A.M., 2004, Identification of the epitope for the epidermal growth factor receptor-specific monoclonal antibody 806 reveals that it preferentially recognizes an untethered form of the receptor, Journal of Biological Chemistry, vol 279, issue 29, American Society for Biochemistry and Molecular Biology, Inc., Bethesda MD USA, pp. 30375-30384.

Faux, M.C., Ross, J.L., Meeker, C., Johns, T.G., Ji, H., Simpson, R.J., Layton, M.J., Burgess, A.W., 2004, Restoration of full-length adenomatous polyposis coli (APC) protein in a colon cancer cell line enhances cell adhesion, Journal of Cell Science, vol 117, issue Pt 3, The Company of Biologists Ltd., UK, pp. 427-439.

Luwor, R.B., Zhu, H., Walker, F., Vitali, A.A., Perera, R.M., Burgess, A.W., Scott, A.M., Johns, T.G., 2004, The tumor-specific de2-7 epidermal growth factor receptor (EGFR) promotes cells survival and heterodimerizes with the wild-type EGFR, Oncogene, vol 23, issue 36, Nature Publishing Group, UK, pp. 6095-6104.

Jungbluth, A.A., Stockert, E., Su Huang, H., Collins, V.P., Coplan, K., Iversen, K., Kolb, D., Johns, T.G., Scott, A.M., Gullick, W.J., Ritter, G., Cohen, L., Scanlan, M.J., Cavenee, W.K., Old, L.J., 2003, A monoclonal antibody recognizing human cancers with amplification/overexpression of the human epidermal growth factor receptor, Proceedings of the National Academy of Sciences of the United States of America, vol 100, issue 2, National Academy of Sciences, USA, pp. 639-644.

Johns, T.G., Luwor, R.B., Murone, C., Walker, F., Weinstock, J., Vitali, A.A., Perera, R.M., Jungbluth, A.A., Stockert, E., Old, L.J., Nice, E.C., Burgess, A.W., Scott, A.M., 2003, Antitumor efficacy of cytotoxic drugs and the monoclonal antibody 806 is enhanced by the EGF receptor inhibitor AG1478, Proceedings of the National Academy of Sciences of the United States of America, vol 100, issue 26, National Academy of Sciences, USA, pp. 15871-15876.

Liu, Z., Panousis, C., Smyth, F.E., Murphy, R., Wirth, V., Cartwright, G.A., Johns, T.G., Scott, A.M., 2003, Generation of anti-idiotype antibodies for application in clinical immunotherapy laboratory analyses, Hybridoma [P], vol 22, issue 4, Mary Ann Liebert, Inc. Publishers, USA, pp. 219-228.

Clements, C.S., Reid, H.H., Beddoe, T.C., Tynan, F.E., Perugini, M., Johns, T.G., Bernard, C.C.A., Rossjohn, J., 2003, The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis, Proceedings of the National Academy of Sciences of the United States of America, vol 100, issue 19, National Academy of Sciences, Washington USA, pp. 11059-11064.

Johns, T.G., Stockert, E., Ritter, G., Jungbluth, A.A., Su Huang, H., Cavenee, W.K., Smyth, F.E., Hall, C.M., Watson, N., Nice, E.C., Gullick, W.J., Old, L.J., Burgess, A.W., Scott, A.M., 2002, Novel monoclonal antibody specific for the de2-7 epidermal growth factor receptor (EGFR) that also recognizes the EGFR expressed in cells containing amplification of the EGFR gene, International Journal of Cancer, vol 98, issue 3, Wiley-Liss, USA, pp. 398-408.

Postgraduate Research Supervisions

Current Supervision

Program of Study:

(DOCTORATE BY RESEARCH).

Thesis Title:

ErbB4: Prognostic significance and theapeutic target in brain cancers.

Supervisors:

Johns, T (Main), Donoghue, J (Associate).