John D. Lewis Research Group

Professor, Department of Oncology
University of Alberta

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.

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.

Whether new discoveries begin at the bedside or the bench, our group is focused on understanding and ultimately curing prostate cancer.

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 described a tetraspanin CD151-specific monoclonal antibody 1A5 that prevents metastasis by inhibiting tumour cell intravasation. We are studying technologies to use this antibody to predict the development of metastatic prostate disease using a simple blood or urine test. 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.

Relevant Publications

See all John Lewis’s publications on PUBMED

1. Ngan, E., Stoletov, K., Smith H.W., Common, J., Muller, W.J., Lewis, J.D. and Siegel, P.M. (2017) LPP is a Src substrate required for invadopodia formation and efficient breast cancer lung metastasis. Nature Communications 8:15059
2. Paproski, R., Jovel, J., Wong, G., Lewis, J.D.*, Zemp, R.J.* (2017) Enhanced detection of cancer biomarkers in blood-borne extracellular vesicles using nanodroplets and focused ultrasound. Cancer Research 77:3-13
3. Potts, K., Irwin, C.R., Favis, N.A., Pink, D.B., Vincent, K.M., Lewis, J.D., Moore, R.B., Hitt, M.H., Evans, D.H. (2017) Oncolytic vaccinia virus deleted in the small subunit of ribonucleotide reductase enhances safety and selectivity in the treatment of bladder cancer. EMBO Molecular Medicine (in press)
4. Luhrs, K.A., Pink, D.S., Zijlstra, A., Lewis, J.D., Parseghian, M.H. (2017) In Vivo Histone H1 Migration from Necrotic to Viable Tissue. Oncotarget 8:16275-29292
5. Mojiri, A., Stoletov, K., Willetts, L., Godbout, R., Jurasz, P., Sergi, C., Eisenstat, D., Lewis, J.D., Jahroudi, N. (2017) Functional assessment of Von Willebrand factor expression by cancer cells of non-endothelial origin. Oncotarget 8:13015-13029
6. Wang, T., Abou-Ouf, H., Hegazy, S.A., Alshalalfa, M., Stoletov, K., Lewis, J.D., Donnelly, B., Bismar, T.A. (2016) Ankyrin G expression is associated with androgen receptor stability, invasiveness, and lethal outcome in prostate cancer patients. Journal of Molecular Medicine 94:1411-1422
7. Willetts L., Bond, D.B., Stoletov, K., Lewis, J.D. (2016) Quantitative Analysis of human Cancer Cell Extravasation Using Intravital Imaging. Methods in Molecular Biology 1458:27-37.
8. , W. Paproski, R., Shao, P., Forbrich, A., Lewis, J.D., Zemp, R.J. (2016) Validating tyrosinase homologue melA as a photoacoustic reporter gene for imaging Escherichia coli. Journal of Biomedical Optics 20:106008.
9. Paproski, R., Forbrich, A., Huynh, E., Chen, J., , J.D., Zheng, G., Zemp, R.J. (2016) Porphyrin Nanodroplets: Submicron Ultrasound and Photoacoustic Contrast Imaging Agents. Small 12:371-80.
10. 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 69:734-44.
11. 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 7:1547-60.
12. 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.
13. Stoletov, K., Lewis, J.D. (2015) Invadopodia: a new therapeutic target to block cancer metastasis. Expert Review of Anticancer Therapy 15:733-5.
14. 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.
15. 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.
16. 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, doi:10.1038/srep06315.
    
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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 .
24. 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.
25. 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.
26. 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.
27. 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.
28. Shukla, S., Ablack, A.L., Wen, A.M., Lee, K., Lewis, J.D. and Steinmetz, N.F. (2013) Increased tumor homing and tissue penetration of the filamentous plant viral nanoparticle Potato virus X. Molecular Pharmaceutics 10:33.42.
29. 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).
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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)
    
37. 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.
38. 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.
39. 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)
40. 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.
41. 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.
42. 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)
    
43. 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)
44. 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.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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) (Faculty of 1000 Must Read)
52. 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)