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Experimental Oncology

John Lewis

Associate Professor,
Frank and Carla Sojonky Chair
in Prostate Cancer Research
Experimental Oncology
Department of Oncology
University of Alberta
5-142 Katz Group Centre
114 Street & 87 Avenue
Edmonton, Alberta T6G 2E1
Tel: 780.492.6113
jdlewis@ualberta.ca

Profile

 

Translational Prostate Cancer Research Group

We study prostate cancer, the most commonly diagnosed cancer in Canadian men. Our goal is to foster an environment where scientists, doctors and clinical researchers work together to address key challenges in prostate cancer care. As a team, we hope to accelerate the transfer of research discoveries from the "bench to the bedside" to make an impact on those living with cancer.

 
To achieve this, we recognize the importance of training future researchers with the skills to work on the threshold between discovery and applied research. This is facilitated by regular multidisciplinary team meetings to discuss research projects, new innovations and clinical trials.
 
Our research program is supported by public funds and fundraised dollars, and much of the progress we've made to date would not have been possible without this support. Members of the group are actively involved in community outreach activities, and we regularly attend community awareness and fundraising events to share the good news stories of our research efforts.
 
Whether new discoveries begin at the bedside or the bench, our group is focused on understanding and ultimately curing aggressive prostate cancer.
 

Alberta Prostate Cancer Research Initiative (APCaRI)

APCaRI brings together a multi-disciplinary team of prostate cancer scientists, physicians, patients, healthcare employees and an international collaborative network together to positively impact the outcomes and quality of life of those living with prostate cancer by accelerating the translation of new research ideas from the laboratory to the clinic.
 
 
APCaRI logo.png

 

Research Interests

The Lewis lab utilizes real-time intravital imaging of the tumour microenvironment to learn about the critical steps of cancer progression, including the growth of new blood vessels and the gain of tumour cell motility that leads to metastasis. We are investigating novel nanoparticles that are being developed for the early detection of prostate cancer, drug delivery, and the in vivo study of tumour cell invasion and metastasis. Connecting these intimately related projects is an integrated research platform that we've developed for long term time-lapse intravital imaging of human cancer progression.
 
Homing in on cancer: platforms for targeted imaging and drug delivery
 
Nanoparticles are a novel class of agents that take advantage of innovative advances in nanotechnology for the development of therapeutics, vaccines and imaging tools. In 2006, we were the first to describe nanoparticles based on the plant virus Cowpea mosaic virus (CPMV) as tools for intravital vascular imaging, and we have since developed a complementary platform for screening nanoparticle formulations in human tumour xenografts. We and others have described the attachment of a variety of functional groups to viruses and other nanoparticles, and have been working in recent years to adapt this platform for prostate cancer imaging and drug delivery. Several nanoparticle platforms under development are promising candidates for the development of prostate cancer imaging and therapeutic agents.
 
tumourtargeting.gif
 
Intravital imaging of nanoparticle (red) uptake in a vascularized (blue) human tumour xenograft (green)
 
Relevant publications
 
Luhrs, K.A., Pink, D.S., Zijlstra, A., Lewis, J.D., Parseghian, M.H. (2015) In Vivo Histone H1 Migration from Necrotic to Viable Tissue. Cancer Research (in press)
 
Paproski, R., Forbrich, A., Huynh, E., Chen, J., Lewis., J.D., Zheng, G., Zemp, R.J. (2015) Porphyrin Nanodroplets: Submicron Ultrasound and Photoacoustic Contrast Imaging Agents. Small (in press)
 
Esguerra, K.V.E., Akentieva, N., Cho, C.F., Lewis, J.D., Turley, E.A., Luyt, L.G. (2015) Identification, Design and Synthesis of Tubulin-Derived Peptides as Novel High Affinity Ligands for the Receptor for Hyaluronan-Mediated Motility (RHAMM/HMMR). Integrative Biology (ePub ahead of print)
 
Paproski, R., Li, Y., Barber, Q., Lewis, J.D., Campbell, R.E., Zemp, R.J. (2015) Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli. Journal of Biomedical Optics (in press)
 
Pink, D.S., Luhrs, K.A., Schulte, W., Chase, J., Zhou, L., Frosch, C., Haberl, U., Roy, A.I., Nguyen, V., Lewis, J.D., Zijlstra, A., Parseghian, M.H. (2015) High efficacy vasopermeability drug candidates identified by screening in an ex ovo chorioallantoic membrane model. Scientific Reports 5:15756.
 
Farhan, M.A., Carmine-Simmen, K., Lewis, J.D., Moore, R.B., Murray, A.G. (2015) Endothelial Cell mTOR Complex-2 Regulates Sprouting Angiogenesis. PLoS ONE 10(8):e0135245.
 
Veiseh, M., Kwon, D.H., Borowsky, A.D., Toelg, C., Leong, H.S., Lewis, J.D., Turley, E.A., Bissell, M.J. (2014) Cellular Heterogeneity Profiling by Hyaluronan Probes Reveals an Invasive but Slow-growing Breast Tumor Subset. Proceedings of the National Academy of Sciences USA. 111:1731-9.
 
Cho, C.F., Wen, A., St. Amant, S., Luyt, L.G., Steinmetz, N.F., Lewis, J.D. (2014) Molecular targeted viral nanoparticles as tools for imaging cancer. Methods in Molecular Biology 1108:211-30.
 
Kain, K.H., Miller, J.W.I., Jones-Paris, C.R., Thomason, R.T., Lewis, J.D., Bader, D., Barnett, J., Zijlstra, A. (2014) The chick embryo as an expanding experimental model for cancer and cardiovascular research. Developmental Dynamics 243:216-228.
 
Townson, J.L., Lin, Y.S., Agola, J.O., Carnes, E.C., Leong, H.S., Lewis, J.D., Haynes, C.L., Brinker, C.J. (2013) Re-Examining the Size/Charge Paradigm: Differing In Vivo Characteristics of Size and Charge-Matched Mesoporous Silica Nanoparticles. J Am Chem Soc 135:16030–16033.
 
Cho, C.F., Azad, B., Luyt, L.G. and Lewis, J.D. (2013) High throughput screening of one-bead-one-compound peptide libraries using intact cells. ACS Combinatorial Science 15:393-400.
 
Cho, C.F., Amadei, G., Breadner, D., Luyt, L., Lewis, J.D. (2012) The discovery of novel integrin ligands from combinatorial libraries using a multiplex ‘beads on a bead’ approach. Nano Letters 12:5957-65. (Highlighted in Canadian Chemical News 65, 19).
 
Shukla, S., Ablack, A.L., Wen, A.M., Lee, K., Lewis, J.D. and Steinmetz, N.F. (2012) Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle Potato virus X. Molecular Pharmaceutics 10:33.42.
 
Pink, D., Schulte, W., Parseghian, M., Zijlstra, A., Lewis, J.D. (2012) Real-time visualization and quantitation of vascular integrity and vascular permeability in vivo: implications for drug delivery. PLoS ONE 7(3): e33760.
 
Lewis, J.D., Zijlstra, A. (2012) “Visualization and quantification of de novo angiogenesis in ex ovo chicken embryos” The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications. Eds. Frank Cuttitta and Enrique Zudaire. Springer.
 
Steinmetz, N.F., Ablack, A., Hickey, J.L., Ablack, J., Manocha, B., Mymryk, J.S., Luyt, L.G., Lewis, J.D. (2011) Intravital imaging of human prostate cancer using bombesin-targeted viral nanoparticles. Small 7:1664-72. (Cover Article)
 
Cho, C.F., Ablack, A., Leong, H.S., Zijlstra, A., Lewis, J.D. (2011) Evaluation of nanoparticle uptake in tumors in real time using intravital imaging. Journal of Visualized Experiments 52: doi: 10.3791/2808. (Highlighted in Biotechniques, May 2012)
 
Steinmetz, N.F., Cho, C.F., Ablack, A., Lewis, J.D., Manchester, M.M. (2011) CPMV nanoparticles target surface vimentin on cancer cells. Nanomedicine 6:351-64.
 
Leong, H.S., Steinmetz, N.F., Ablack, A., Destito, G., Zijlstra, A., Stuhlmann, H., Manchester, M., Lewis, J.D.  (2010) Intravital imaging of embryonic and tumor neovasculature using viral nanoparticles. Nature Protocols 8:1406-17.
 
Brunel, F., Lewis, J.D., Destito, G., Steinmetz, N.F., Manchester, M.A., Stuhlmann, H., and Dawson, P. (2010) Hydrazone ligation strategy to assemble multifunctional viral nanoparticles for cell imaging and tumor targeting. Nano Letters 10:1093-1097.
 
Martin, A.L., Hickey, J.L., Ablack, A., Lewis, J.D., Luyt, L.G., Gillies, E.R. (2010) Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells. Journal of Nanoparticle Research 12:1599-1608.
 
Amadei, G.A., Cho, C.F., Lewis, J.D., Luyt, L.G. (2010) A Fast, Reproducible And Low-Cost Method For Sequence Deconvolution Of “On-Bead” Peptides Via “On-Target” Maldi-TOF/TOF Spectrometry. Journal of Mass Spectrometry 45:241-251.
 
Lewis, J.D., Destito, G., Zijlstra, A., Gonzalez, M.J., Quigley, J.P., Manchester, M.A., and Stuhlmann, H. (2006) Viral nanoparticles (VNPs) as tools for intravital vascular imaging. Nature Medicine 12:354-360. (Highlighted in Cell 125, 6-7)

 
 
Cancer metastasis: strategies to detect and block the spread of cancer
 
Like other cancers, prostate cancer becomes deadly when it spreads, or metastasizes. We have been interested for some time in learning more about the genes and proteins that cause prostate cancer to spread. With our collaborators, we have recently shown that tetraspanin CD151-specific monoclonal antibody 1A5 prevents metastasis by inhibiting tumour cell intravasation. We have begun to evaluate the ability of this CD151 antibody to predict the development of metastatic prostate disease from patient biopsies. We would like in the short-term to develop a better test for prostate cancer that accurately predicts its spread, and in the long term to develop new drugs to block metastasis completely. We hope that these advances will make a significant impact on those living with prostate cancer.
 
 
 Tumour2.gifmetastasis2.gif
 
Intravital imaging of a human tumour and micrometasis growing in vivo over 20 hours
 
Relevant publications
 
Kinnaird, A., Dromparis, P., Saleme, B., Gurtu, V., Watson, K., Paulin, R., Zervopoulos, S., Stenson, T., Sutendra, G., Pink, D.S., Carmine-Simmen, K., Moore, R.B., Lewis, J.D., Michelakis, E. (2015) Metabolic Modulation of Clear Cell Renal Cell Carcinoma with Dichloroacetate, an Inhibitor of Pyruvate Dehydrogenase Kinase. European Urology (ePub ahead of print)
 
Stoletov, K., Lewis, J.D. (2015) Invadopodia: a new therapeutic target to block cancer metastasis. Expert Review of Anticancer Therapy 15:733-5.
 
Leong, H.S., Robertson, A.E., Stoletov, K., Leith, S.J., Chin, C.A., Chien, A.E., Hague, M.N., Ablack, A.L., Carmine Simmen, K., MacPherson, V.A., Postenka, C.O., Turley, E.A., Courtneidge, S.A., Chambers, A.F., Lewis, J.D. (2014) Invadopodia are required for cancer cell extravasation and are a therapeutic target for metastasis. Cell Reports 8:1558-1570.
 
Mathenge, G.E., Dean, C.A., Clements, D., Vaghar-Kashani, A., Photopoulos, S., Coyle, K.M., Giacomantonio, M., Malueth, B., Nunokawa, A., Jordan, J., Lewis, J.D., Gujar, S.A., Marcato, P., Lee, P.W., Giacomantonio, C.A. (2014) Core needle biopsy of breast cancer tumors increases distant metastasis in association with an immunosuppressive microenvironment. Neoplasia 16:950-960.
 
MacMillan, C.D., Leong, H.S., Dales, D.W., Robertson, A.E., Lewis, J.D., Chambers, A.F., Tuck, A.B. (2014) Stage of Breast Cancer Progression Influences Cellular Response to Activation of the WNT/Planar Cell Polarity Pathway. Scientific Reports 4: 6315.
 
Golubkov, V.S., Prigozhina, N.L., Zhang, Y., Stoletov, K., Lewis, J.D., Schwartz, P.E., Hoffman, R.M., Strongin, A.Y. (2014) Protein-tyrosine pseudokinase 7 (PTK7) directs cancer cell motility and metastasis. Journal of Biological Chemistry 289:24238-49.
 
Bendris, N., Cheung, C., Leong, H.S., Lewis, J.D., Chambers, A.F., Blanchard, J.M. (2014) Cyclin A2, a novel regulator of EMT. Cellular and Molecular Life Sciences 71:4881-94.
 
Stoletov, K., Bond, D., Hebron, K., Raha, S., Zijlstra, A., Lewis, J.D. (2014) Metastasis as a therapeutic target in prostate cancer: a conceptual framework. Am J Clin Exp Urology 2:45-56.
 
Palmer, T.D., Martinez, C.L., Vasquez, C., Jones-Paris, C., Hebron, K., Chan, S.M., Chalasani, V., Gomez-Lemus J., Williams A.K., Chin, J.L., Ketova, T., Lewis, J.D., Zijlstra A. (2014) Integrin-free tetraspanin CD151 can inhibit tumor cell motility upon clustering and is a clinical indicator of prostate cancer progression. Cancer Research 74:173-187.
 
Fang, C., Avis, I., Bianco, C., Held, N., Morris, J., Ylaya, K., Hewitt, S.M., Aparico, M., Aplin, A.C., Nicosia, R.F., Fung, L.A., Lewis, J.D., Stetler-Stevenson, W.G., Salomon, D.S., Cuttitta, F. (2013) A new peptide amide of the apelinergic family having multifunctional roles in embryogenesis and carcinogenesis. Open J Clin Diag 3:37-51.
 
Cvetkovic, D., Dragan, M., Leith, S.J., Mir, Z.M., Leong, H.S., Pampillo, M., Lewis, J.D., Babwah, A.V., Bhattacharya, M. (2013) KISS1R Induces Invasiveness of Estrogen Receptor-Negative Human Mammary Epithelial and Breast Cancer Cells. Endocrinology 154:1999-2014.
 
Leong, H.S., Lizardo, M.M., Nambiar, S., Ablack, A., Wandless, T., Chambers, A.F., Lewis, J.D. (2012) Imaging the impact of chemically inducible proteins on cellular dynamics in vivo. PLoS ONE 7:e30177.
 
Leong, H.S., Chambers, A.F. and Lewis, J.D. (2012) Assessing cancer cell migration and metastatic growth in vivo in the chick embryo using fluorescence intravital imaging. Methods in Molecular Biology 872:1-14.
 
Penuela, S., Gyenis, L., Ablack, A., Churko, J., Berger, A., Litchfield, D.W., Lewis, J.D., Laird, D.W. (2012) Loss of pannexin 1 attenuates melanoma progression by reversion to a melanocytic phenotype. Journal of Biological Chemistry 287:29184-93.
 
Quail, D.F., Walsh, L.A., Zhang, G., Findlay, S.D., Moreno, J., Fung, L., Ablack, A., Lewis, J.D., Done, S., Hess, D.A. and Postovit, L.M. (2012) Embryonic protein Nodal promotes breast cancer vascularization. Cancer Research 72:3851-3863.
 
Behnam Azad, B., Cho, C.F., Lewis, J.D., Luyt, L. (2012) Synthesis, radiometal labeling and in vitro evaluation of a targeted PPIX derivative. Applied Radiation and Isotopes 70:505-11.
 
Lu, C., McFarland, M.S., Nesbitt, R.L., Williams, A.K., Chan, S., Gomez-Lemus, J., Autran, A.M., Al-Zahrani, A., Chin, J., Izawa, J., Luyt, L.G., Lewis, J.D. (2011) Ghrelin Receptor as a Novel Imaging Target for Prostatic Neoplasms. The Prostate 72:825-33. (Highlighted in Nature Reviews Urology 9, 293)
 
Leong, H.S., Podor, T., Lewis, J.D. (2011) Validation of flow cytometric detection of platelet microparticles and liposomes by atomic force microscopy. Journal of Thrombosis and Haemostasis 9:2466-76.
 
Goulet, B., Chan, G., Chambers, A.F., Lewis, J.D. (2011) An emerging role for the nuclear localization of maspin in the inhibition of tumor progression and metastasis. Biochemistry and Cell Biology 90:22-38.
 
Arpaia, E., Quintela-Fandino, M., Blaser, H., Leong, H.S., Ablack, A., Nambiar, S.C., Lind, E.F., Silvester, J., Fleming, C.K., Rufini A., Tusche, M.W., Brüstle, A., Nadeem, V., Pan, J.J., Lewis, J.D. and Tak W. Mak. (2011) The Interaction between Caveolin-1 and Rho-GTPases Promotes Metastasis by Controlling the Transcription of alpha5-Integrin and the Activation of Src, Ras and Erk. Oncogene 16:884-96.
 
Palmer, T.D., Ashby, W., Lewis, J.D., Zijlstra, A. (2011) Targeting tumor cell motility to prevent metastasis. Advanced Drug Delivery Reviews 63:568-81.
 
Goulet, B., Kennette, W., Ablack, A., Postenka, C.O., Hague, N., Mymryk, J., Tuck, A.B., Giguère, V., Chambers, A.F., Lewis, J.D. (2011) Nuclear Localization of Maspin is Essential for its Inhibition of Tumor Growth and Metastasis. Laboratory Investigation 91:1181-1187. (Cover Article)
 
Palmer, T., Lewis, J.D., Zijlstra, A. (2011) Quantitative analysis of tumor cell dissemination using an avian embryo model. Journal of Visualized Experiments 51: doi: 10.3791/2815.
 
Chambers A.F., Turley, E.A., Lewis, J.D., Luyt, L.G. (2010) “Innovative Preclinical Models for Evaluating Radiopharmaceuticals in Oncology” Antibody and Peptide-Targeted Radiotherapy of Malignancies. Ed. Raymond Reilly. San Francisco: Wiley-Blackwell. (ISBN 978-0-470-24372-5)
 
Zhang, Y., Schulte, W., Pink, D., Zijlstra, A., Lewis, J.D., Waisman, D.M. (2010) Sensitivity of cancer cells to truncated diptheria toxin. PLoS ONE 5: e10498.
 
Zijlstra, A., Lewis, J.D., DeGryse, B., Stuhlmann, H., and Quigley, J.P. (2008) The inhibition of tumour cell intravasation and subsequent metastasis via regulation of in vivo tumour cell motility by the tetraspanin CD151. Cancer Cell 13:221-234. (Cover Article) (Highlighted in Nature Reviews Cancer 8, 326-327)

 

Research Support

 
Alberta Cancer Foundation
Bird Dogs for Prostate Cancer Research
Prostate Cancer Canada
Alberta Innovates Health Solutions
Motorcycle Ride for Dad
National Institutes of Health (USA)
Canadian Institutes of Health Research
Canadian Foundation for Innovation
Canadian Cancer Society

Publications