Assoc Prof Martin Lackmann - Researcher Profile

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Address

Department of Biochemistry & Molecular Biology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Biography

Grand image for tumours and leukaemia

During his research on solid tumours, Associate Professor Martin Lackmann discovered some unexpected possibilities for the development of anti-cancer therapeutics. Martin is Head of the Protein Interaction and Cancer Research Laboratory, which has a focus on basic and translational cancer research. The findings from their current work have great promise for the treatment of solid tumours and leukaemia. 

Martin says his lab has identified molecules that are critical in guiding tumour cell migration and the formation of blood vessels and connective tissue within tumours. They have now used their insights from this fundamental work to devise two promising candidate anti-cancer therapeutics. 

“The first drug candidate is a surface protein that recently entered clinical trials in the US and Melbourne,” Martin says. He and his colleagues initially thought this antibody - which targets a protein that appears on the surface of tumour cells and tumour blood vessels - would only be suitable for solid tumour treatment; they were fortunate to identify leukaemia as an additional target.

“This protein is normally only present during embryonic development. While there’s little or nothing left in adults, the protein reappears, particularly when tumour vessels are forming. Because growing tumours have a need for blood and nutrients, the protein reappears to guide new cells into the blood vessels of the tumour. 

“The antibody works by stopping the cells, so vessels do not form and the tumour stops growing because it’s deprived of nutrients. Fortuitously, this molecule was also found on leukaemic stem cells, where binding of the antibody will kill them. Current clinical trials of the antibody are being conducted in leukaemia patients, and are open to patients at the Alfred Hospital,” he says.

“The lab’s second candidate, which is still in early development, will most likely target solid tumours. It’s a protease which was considered as a tumour drug some years ago. The drugs developed so far against this protease haven’t been specific enough, so they didn’t succeed in the clinic. We’ve identified another mechanism to target the protease with a monoclonal antibody. We’re currently trying to understand the mechanism by which this antibody interferes with the activity of this protease, which is involved in many cancers,” Martin says.

Martin’s lab is developing high-resolution imaging techniques to study the functions of these antibodies. Part of this work involves combining two established approaches to imaging.

“We have developed techniques to image the effect of the antibody in real time using two-photon microscopes, so we can see the disruption of blood vessels while it happens. We’re trying to marry the two-photon microscope with imaging by computed tomography (CT). Imaging with the two-photon microscope is very high-resolution and it allows you to see the cells targeted by the antibody. 

“We plan to use CT to identify exactly where the tumour and blood vessels are, so we can use the two-photon microscope to zoom in from a low-resolution image into a high-resolution image. We’re also developing technologies that can merge images from these unrelated instruments.” 

Martin hopes improved imaging of this antibody may lead to earlier detection of tumours.

“The cells, which populate the tumour and provide its blood vessels and architecture, come out of the bone marrow and are therefore present in the patient’s blood. This means we can use our antibody to detect them in blood samples. We’re currently screening normal and tumour patient populations in collaboration with clinics around Melbourne. 

“We are hopeful of using this method to test tumour patients after they are cleared. After a surgeon has cut a tumour out, you know it’s gone, but you often don’t know if it has reappeared until it’s too late. Finding markers in the blood, which is easily accessible, is an attractive solution to this problem,” Martin says.

Qualifications

DOCTOR OF PHILOSOPHY
Institution: University of Sydney
Year awarded: 1992

Publications

Book Chapters

Lackmann, M., 2010, Mechanisms and functions of Eph receptor signaling, in Handbook of Cell Signaling, eds Ralph A Bradshaw and Edward A Dennis, Academic Press, USA, pp. 443-449.

Journal Articles

Atapattu Mudiyanselage, L.S., Saha, N., Llerena, C.O., Vail, M.E., Scott, A.M., Nikolov, D.B., Lackmann, M., Janes, P.W., 2012, Antibodies binding the ADAM10 substrate recognition domain inhibit Eph function, Journal Of Cell Science [P], vol 125, issue Pt 24, The Company of Biologists Ltd, UK, pp. 6084-6093.

Janes, P.W., Nievergall, E., Lackmann, M., 2012, Concepts and consequences of Eph receptor clustering, Seminars In Cell & Developmental Biology [P], vol 23, issue 1, Academic Press, UK, pp. 43-50.

Coulthard, M.G., Morgan, M., Woodruff, T.M., Arumugam, T., Taylor, S.M., Carpenter, T.C., Lackmann, M., Boyd, A.W., 2012, Eph/Ephrin signaling in injury and inflammation, American Journal Of Pathology [P], vol 181, issue 5, Elsevier Inc., USA, pp. 1493-1503.

Nievergall, E., Saunders, T., Lackmann, M., 2012, Targeting of EPH receptor tyrosine kinases for anticancer therapy, Critical Reviews in Oncogenesis [P], vol 17, issue 2, Begell House Inc., USA, pp. 211-232.

Janes, P.W., Griesshaber, B., Atapattu Mudiyanselage, L.S., Nievergall, E., Hii, L.L., Mensinga, A., Chheang, C., Day, B.W., Boyd, A.W., Bastiaens, P.I., Jorgensen, C., Pawson, T., Lackmann, M., 2011, Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors, Journal of Cell Biology [P], vol 195, issue 6, Rockefeller University Press, USA, pp. 1033-1045.

Nievergall, E., Lackmann, M., Janes, P.W., 2011, Eph-dependent cell-cell adhesion and segregation in development and cancer, Cellular And Molecular Life Sciences [P], vol E, Birkhaeuser Verlag AG, Switzerland, pp. 1-30.

Himanen, J., Yermekbayeva, L., Janes, P.W., Walker, J.R., Xu, K., Atapattu Mudiyanselage, L.S., Rajashankar, K.R., Mensinga, A., Lackmann, M., Dhe-Paganon, S., Nikolov, D.B., 2010, Architecture of Eph receptor clusters, Proceedings Of The National Academy Of Sciences O..., vol 107, issue 24, National Academy of Sciences, USA, pp. 10860-10865.

Nievergall, E., Janes, P.W., Stegmayer, C., Vail, M.E., Haj, F.G., Teng, S.W., Neel, B.G., Bastiaens, P.I., Lackmann, M., 2010, PTP1B regulates Eph receptor function and trafficking, Journal of Cell Biology [P], vol 191, issue 6, Rockefeller University Press, USA, pp. 1189-1203.

Janes, P.W., Wimmer-Kleikamp, S.H., Frangakis, A.S., Treble, K., Griesshaber, B., Sabet, O., Grabenbauer, M., Ting, A.Y., Saftig, P., Bastiaens, P.I., Lackmann, M., 2009, Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10, Plos Biology [P], vol 7, issue 10, Public Library of Science, USA, pp. e1000215-1-e1000215-17.

Papageorgiou, I., Nicholls, P.K., Wang, F., Lackmann, M., Makanji, Y., Salamonsen, L.A., Robertson, D., Harrison, C.B., 2009, Expression of nodal signalling components in cycling human endometrium and in endometrial cancer, Reproductive Biology and Endocrinology [P], vol 7, issue 122, BioMed Central Ltd, UK, pp. 1-11.

Wimmer-Kleikamp, S.H., Nievergall, E., Gegenbauer, K., Adikari, S.H., Mansour, M., Yeadon, T., Boyd, A.W., Patani, N.R., Lackmann, M., 2008, Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells, Blood, vol 112, issue 3, American Society of Hematology, United States, pp. 721-732.

Lackmann, M., Boyd, A.W., 2008, Eph, a protein family coming of age: More confusion, insight, or complexity?, Science Signaling, vol 1, issue 15, American Association for the Advancement of Science, USA, pp. re2 (1)-re2 (16).

Janes, P.W., Adikari, S.H., Lackmann, M., 2008, Eph/ephrin signalling and function in oncogenesis: Lessons from embryonic development, Current Cancer Drug Targets, vol 8, issue 6, Bentham Science Publishers Ltd., Netherlands, pp. 473-489.

Nikolov, D.B., Li, C., Lackmann, M., Jeffrey, P., Himanen, J., 2007, Crystal structure of the human ephrin-A5 ectodomain, Protein Science, vol 16, issue 5, Cold Spring Harbor Lab Press, Publications Department, Woodbury NY USA, pp. 996-1000.

Day, B.W., Smith, F.M., Chen, K., McCarron, J.K., Herath, N.I., Lackmann, M., Boyd, A.W., 2006, Eph/ephrin membrane proteins: a mammalian expression vector pTIg-BOS-Fc allowing rapid protein purification, Protein & Peptide Letters, vol 13, issue 2, Bentham Science Publishers Ltd, Sharjah UAE, pp. 193-196.

Janes, P.W., Saha, N., Barton, W.A., Kolev, M.V., Wimmer-Kleikamp, S.H., Nievergall, E., Blobel, C.P., Himanen, J., Lackmann, M., Nikolov, D.B., 2005, Adam Meets Eph: An ADAM Substrate Recognition Module Acts as a Molecular Switch for Ephrin Cleavage In trans, Cell, vol 123, issue 2, Cell Press, Cambridge MA USA, pp. 291-304.

Vearing, C.J., Lee, F., Wimmer-Kleikamp, S.H., Spirkoska, V., To, C., Stylianou, C., Spanevello, M., Brechbiel, M., Boyd, A.W., Scott, A.M., Lackmann, M., 2005, Concurrent binding of anti-EphA3 antibody and Ephrin-A5 amplifies EphA3 signaling and downstream responses: potential as EphA3-specific tumor-targeting reagents, Cancer Research, vol 65, issue 15, American Association of Cancer Research, Philadelphia USA, pp. 6745-6754.

Vearing, C.J., Lackmann, M., 2005, Eph receptor signalling; dimerisation just isn't enough, Growth Factors, vol 23, issue 1, Taylor & Francis Ltd, Abingdon England, pp. 67-76.

Wimmer-Kleikamp, S.H., Lackmann, M., 2005, Eph-modulated cell morphology, adhesion and motility in carcinogenesis, IUBMB Life, vol 57, issue 6, Taylor & Francis Inc., Philadelphia USA, pp. 421-431.

Day, B., To, C., Himanen, J., Smith, F.M., Nikolov, D.B., Boyd, A.W., Lackmann, M., 2005, Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3, Journal of Biological Chemistry, vol 280, issue 28, American Society for Biochemistry & Molecular Biology Inc., Bethesda USA, pp. 26526-26532.

Smith, F.M., Vearing, C., Lackmann, M., Treutlein, H., Himanen, J., Chen, K., Saul, A., Nikolov, D.B., Boyd, A.W., 2004, Dissecting the EphA3/ephrin-A5 interactions using a novel functional mutagenesis screen, Journal of Biological Chemistry, vol 279, issue 10, American Society for Biochemistry and Molecular Biology, Inc., Bethesda USA, pp. 9522-9531.

Wimmer-Kleikamp, S.H., Janes, P.W., Squire, A., Bastiaens, P.I.H., Lackmann, M., 2004, Recruitment of Eph receptors into signaling clusters does not require ephrin contact, The Journal of Cell Biology, vol 164, issue 5, Rockefeller University Press, New York USA, pp. 661-666.

Himanen, J., Chumley, M.J., Lackmann, M., Li, C., Barton, W.A., Jeffrey, P.D., Vearing, C.J., Geleick, D., Feldheim, D.A., Boyd, A.W., Henkemeyer, M., Nikolov, D.B., 2004, Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling, Nature Neuroscience, vol 7, issue 5, Nature Publishing Group, New York USA, pp. 501-509.

Wilson-Annan, J., O'Reilly, L.A., Crawford, S.A., Hausmann, G., Beaumont, J.G., Parma, L.P., Chen, L., Lackmann, M., Lithgow, T.J., Hinds, M.G., Day, C.L., Adams, J.M., Huang, D.C.S., 2003, Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity, The Journal of Cell Biology, vol 162, issue 5, Rockefeller University Press, USA, pp. 877-887.

Lawrenson, I.D., Wimmer-Kleikamp, S.H., Lock, P., Schoenwaelder, S.M., Down, M., Boyd, A.W., Alewood, P.F., Lackmann, M., 2002, Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling, Journal of Cell Science, vol 115, issue 5, Company of Biologists Ltd, Cambridge England, pp. 1059-1072.

Lawrenson, I.D., Wimmer-Kleikamp, S.H., Lock, P., Schoenwaelder, S.M., Down, M., Boyd, A.W., Alewood, P., Lackmann, M., 2002, Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by Crkll and Rho-mediated signalling, Journal of Cell Science, vol 115, The Company of Biologists Ltd, UK, pp. 1059-1072.

Coulthard, M.G., Duffy, S., Down, M., Evans, B., Power, M., Smith, F.M., Stylianou, C., Wimmer-Kleikamp, S.H., Oates, A., Lackmann, M., Burns, G.F., Boyd, A.W., 2002, The role of the Eph-ephrin signalling system in the regulation of developmental patterning, International Journal of Developmental Biology, vol 46, issue 4, U B C Press, Univ Basque Country, Editorial Services, Bilbao Spain, pp. 375-384.

Himanen, J., Rajashankar, K.R., Lackmann, M., Cowan, C.A., Henkemeyer, M., Nikolov, D.B., 2001, Crystal structure of an Eph receptor-ephrin complex, Nature, vol 414, issue 6866, Nature Publishing Group, London UK, pp. 933-938.

Conference Proceedings

Hossain, T., Lv, G., Teng, S., Lu, G., Lackmann, M., 2011, Improved Symmetric-SIFT for multi-modal image registration, 2011 International Conference on Digital Image Computing: Techniques and Applications (DICTA 2011), 6 December 2011 to 8 December 2011, IEEE Computer Society, Los Alamitos CA USA, pp. 197-202.

Lv, G., Hossain, T., Teng, S., Lu, G., Lackmann, M., 2011, Improving SIFT's performance by incorporating appropriate gradient information, 26th Image and Vision Computing New Zealand Conference (IVCNZ 2011), 29 November 2011 to 1 December 2011, Patrice Delmas, Jason James and Burkhard Wuensche, Auckland New Zealand, pp. 381-386.

Nguyen, H., Abramson, D., Bethwaite, B., Dinh, N., Enticott, C., Garic, S., Russel, A., Firth, S., Harper, I., Lackmann, M., Vail, M., Schek, S., 2011, Integrating scientific workflows and large tiled display walls: Bridging the visualization divide, Proceedings of the 2011 International Conference on Parallel Processing Workshops, 13 September 2011 to 16 September 2011, IEEE Computer Society, Los Alamitos CA USA, pp. 308-316.

Russel, A., Abramson, D.A., Bethwaite, B., Dinh, N.M., Enticott, C.M., Firth, S.D., Garic, S., Harper, I.S., Lackmann, M., Schek, S., Vail, M.E., 2010, An abstract virtual instrument system for high throughput automatic microscopy, Proceedings of the International Conference on Computational Science, 31 May 2010 to 02 June 2010, Elsevier, Amsterdam Netherlands, pp. 545-554.

Hossain, T., Teng, S., Lu, G., Lackmann, M., 2010, An enhancement to SIFT-based techniques for image registration, Proceedings of the 2010 Digital Image Computing: Techniques and Applications, 01 December 2010 to 03 December 2010, IEEE Computer Society, Los Alamitos CA USA, pp. 166-171.

Abramson, D.A., Bethwaite, B., Dinh, N.M., Enticott, C.M., Firth, S.D., Garic, S., Harper, I.S., Lackmann, M., Nguyen, H.A., Ramdas, T., Russel, A., Schek, S., Vail, M.E., 2009, Virtual microscopy and analysis using scientific workflows, Proceedings of the 2009 Fifth IEEE International Conference on e-Science, 09 December 2009 to 11 December 2009, IEEE Computer Society, Los Alamitos CA USA, pp. 239-246.

Other

Lackmann, M., Janes, P.W., Nikolov, D.B., Saha, N., 2010, Regulation of metalloprotease cleavage of cell surface proteins, Australia.

Vearing, C., Wimmer-Kleikamp, S.H., Boyd, A.W., Scott, A.M., Lackmann, M., 2009, Eph/ephrin mediated modulation of cell adhesion and tumour cell metastasis, Australia.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Supervisors:
Lu, G (Main), Lackmann, M (Associate), Teng, S (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Effective and efficient techniques for contour-based corner detection and description for image matching.
Supervisors:
Teng, S (Main), Lackmann, M (Associate), Lu, G (Associate).
Program of Study:
(POSTGRADUATE QUALIFYING OR PRELIMINARY).
Thesis Title:
Effects of a function-blocking mono-clonal antibody against the ADAMIO metalloprotease on oncogenic signalling mechanisms.
Supervisors:
Janes, P (Joint), Lackmann, M (Joint-co).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
The role of mRNA poly (A)-tail length regulation in translational repression..
Supervisors:
Lackmann, M (Main), Devenish, R (Associate), Janes, P (Associate).

Completed Supervision

Student:
Nievergall, E.
Program of Study:
Regulation of EphA3 receptor tyrosine kinase signalling by protein tyrosine phosphatases. (PHD) 2012.
Supervisors:
Lackmann, M (Main), Janes, P (Associate).