Publications
High impact and peer-reviewed. Check out our latest published research.
Publications
High impact and peer-reviewed. Check out our latest published research.
Featured Articles
Modeling human brain tumors in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets
Uswa Shahzad, Michael S Taccone, Sachin A Kumar, Hidehiro Okura, Stacey Krumholtz, Joji Ishida, Coco Mine, Kyle Gouveia, Julia Edgar, Christian Smith, Madeline Hayes, Xi Huang, W Brent Derry, Michael D Taylor, James T Rutka
Neuro-Oncology, Volume 23, Issue 5 (2021)
For decades, cell biologists and cancer researchers have taken advantage of non-murine species to increase our understanding of the molecular processes that drive normal cell and tissue development, and when perturbed, cause cancer. The advent of whole-genome sequencing has revealed the high genetic homology of these organisms to humans. Seminal studies in non-murine organisms such as Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio identified many of the signalling pathways involved in cancer. Studies in these organisms offer distinct advantages over mammalian cell or murine systems. Compared to murine models, these three species have shorter lifespans, are less resource intense, and are amenable to high-throughput drug and RNA interference screening to test a myriad of promising drugs against novel targets. In this review, we introduce species-specific breeding strategies, highlight the advantages of modeling brain tumours in each and underscore the successes attributed to scientific investigation using these models. Discoveries in the fields of cancer research and in particular neuro-oncology, may be expedited using these powerful screening tools and strategies.
Diffuse intrinsic pontine glioma: Current insights and future directions
Dilakshan Srikanthan, Michael S Taccone, Randy Van Ommeran, Joji Ishida, Stacey Krumholtz, James T Rutka
Chinese Neurosurgical Journal, Volume 7, Article 6 (2021)
Diffuse intrinsic pontine glioma (DIPG) is a lethal paediatric brain tumour and the leading cause of brain tumour–related death in children. As several clinical trials over the past few decades have led to no significant improvements in outcome, the current standard of care remains fractionated focal radiation. Due to the recent increase in stereotactic biopsies, tumour tissue availabilities have enabled our advancement of the genomic and molecular characterization of this lethal cancer. Several groups have identified key histone gene mutations, genetic drivers, and methylation changes in DIPG, providing us with new insights into DIPG tumourigenesis. Subsequently, there has been increased development of in vitro and in vivo models of DIPG which have the capacity to unveil novel therapies and strategies for drug delivery. This review outlines the clinical characteristics, genetic landscape, models, and current treatments and hopes to shed light on novel therapeutic avenues and challenges that remain. With an increasing understanding of its molecular genetics, a growing number of promising preclinical models, and novel techniques to overcome the limitations of effective drug delivery across the BBB, it is our hope that the future of DIPG therapy will change dramatically in a relatively short time, much to the benefit of children who harbour this devastating brain tumour.
MRI-guided focused ultrasound enhances drug delivery in experimental diffuse intrinsic pontine glioma
Joji Ishida, Saira Alli, Andrew Bondoc, Brian Golbourn, Nesrin Sabha, Kristina Mikloska, Stacey Krumholtz, Dilakshan Srikanthan, Naohide Fujita, Amanda Luck, Colin Maslink, Christian Smith, Kullervo Hynynen, James Rutka
Journal of Controlled Release, Volume 330 (2021)
Diffuse intrinsic pontine glioma (DIPG) is a surgically unresectable and devastating tumour in children. To date, there are no effective chemotherapeutics despite a myriad of clinical trials. The intact blood-brain barrier (BBB) is likely responsible for the limited clinical response to chemotherapy. MRI-guided focused ultrasound (MRgFUS) is a promising non-invasive method for treating CNS tumours. Moreover, MRgFUS allows for the temporary and repeated disruption of the BBB. Our group previously reported the feasibility of temporary BBB opening within the normal murine brainstem using MRgFUS following intravenous (IV) administration of microbubbles. In the current study, we set out to test the effectiveness of targeted chemotherapy when paired with MRgFUS in murine models of DIPG. Following IV administration of doxorubicin, MRgFUS-treated animals exhibited a 4-fold higher concentration of drug within the brainstem tumours compared to controls. Moreover, the volumetric tumour growth rate was significantly suppressed. These data provide critical support for clinical trials investigating MRgFUS-mediated BBB opening, which may ameliorate DIPG chemotherapeutic approaches in children.
Dive Deeper.
A full list of our publications by year. Click any title to read the full article.
2021
Ishida, J., Alli, S., Bondoc, A., Golbourn, B., Sabha, N., Mikloska, K., Krumholtz, S., Srikanthan, D., Fujita, N., Luck, A., Maslink, C., Smith, C., Hynynen, K., & Rutka, J. (2021). MRI-guided focused ultrasound enhances drug delivery in experimental diffuse intrinsic pontine glioma Journal of Controlled Release, 330, 1034–1045.Journal of Controlled Release, 330, 1034–1045.Journal of Controlled Release, 330, 1034–1045.Journal of Controlled Release, 330, 1034–1045.
Shahzad, U., Taccone, M. S., Kumar, S. A., Okura, H., Krumholtz, S., Ishida, J., Mine, C., Gouveia, K., Edgar, J., Smith, C., Hayes, M., Huang, X., Derry, W. B., Taylor, M. D., & Rutka, J. T. (2021). Modeling human brain tumors in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets. Neuro-Oncology, 23(5), 718–731.Neuro-Oncology, 23(5), 718–731.Neuro-Oncology, 23(5), 718–731.Neuro-Oncology, 23(5), 718–731.
Srikanthan, D., Taccone, M. S., Van Ommeren, R., Ishida, J., Krumholtz, S. L., & Rutka, J. T. (2021). Diffuse intrinsic pontine glioma: Current insights and future directions. 6.
2020
Wong, R., Gong, H., Alanazi, R., Bondoc, A., Luck, A., Sabha, N., Horgen, F. D., Fleig, A., Rutka, J. T., Feng, Z.-P., & Sun, H.-S. (2020). Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions. Cell Calcium, 92, 102307.
2018
Alli, S., Figueiredo, C. A., Golbourn, B., Sabha, N., Wu, M. Y., Bondoc, A., Luck, A., Coluccia, D., Maslink, C., Smith, C., Wurdak, H., Hynynen, K., O’Reilly, M., & Rutka, J. T. (2018). Brainstem blood brain barrier disruption using focused ultrasound: A demonstration of feasibility and enhanced doxorubicin delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society, 281, 29–41.
Bertrand, K. C., Faria, C. C., Skowron, P., Luck, A., Garzia, L., Wu, X., Agnihotri, S., Smith, C. A., Taylor, M. D., Mack, S. C., & Rutka, J. T. (2018). A functional genomics approach to identify pathways of drug resistance in medulloblastoma. Acta Neuropathologica Communications, 6(1), 146.
Coluccia, D., Figueiredo, C. A., Wu, M. Y., Riemenschneider, A. N., Diaz, R., Luck, A., Smith, C., Das, S., Ackerley, C., O’Reilly, M., Hynynen, K., & Rutka, J. T. (2018). Enhancing glioblastoma treatment using cisplatin-gold-nanoparticle conjugates and targeted delivery with magnetic resonance-guided focused ultrasound. Nanomedicine: Nanotechnology, Biology, and Medicine, 14(4), 1137–1148.
Diaz, R. J., Luck, A., Bondoc, A., Golbourn, B., Picard, D., Remke, M., Loukides, J., Sabha, N., Smith, C., Cusimano, M. D., & Rutka, J. T. (2018). Characterization of a Clival Chordoma Xenograft Model Reveals Tumor Genomic Instability. The American Journal of Pathology, 188(12), 2902–2911.
2017
Lassaletta, A., Zapotocky, M., Mistry, M., Ramaswamy, V., Honnorat, M., Krishnatry, R., Guerreiro Stucklin, A., Zhukova, N., Arnoldo, A., Ryall, S., Ling, C., McKeown, T., Loukides, J., Cruz, O., de Torres, C., Ho, C.-Y., Packer, R. J., Tatevossian, R., Qaddoumi, I., … Tabori, U. (2017). Therapeutic and Prognostic Implications of BRAF V600E in Pediatric Low-Grade Gliomas. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 35(25), 2934–2941.
2016
Coluccia, D., Figuereido, C., Isik, S., Smith, C., & Rutka, J. T. (2016). Medulloblastoma: Tumor Biology and Relevance to Treatment and Prognosis Paradigm. Current Neurology and Neuroscience Reports, 16(5), 43.
Agnihotri, S., Golbourn, B., Huang, X., Remke, M., Younger, S., Cairns, R. A., Chalil, A., Smith, C. A., Krumholtz, S.-L., Mackenzie, D., Rakopoulos, P., Ramaswamy, V., Taccone, M. S., Mischel, P. S., Fuller, G. N., Hawkins, C., Stanford, W. L., Taylor, M. D., Zadeh, G., & Rutka, J. T. (2016). PINK1 Is a Negative Regulator of Growth and the Warburg Effect in Glioblastoma. Cancer Research, 76(16), 4708–4719.
Okura, H., Golbourn, B. J., Shahzad, U., Agnihotri, S., Sabha, N., Krieger, J. R., Figueiredo, C. A., Chalil, A., Landon-Brace, N., Riemenschneider, A., Arai, H., Smith, C. A., Xu, S., Kaluz, S., Marcus, A. I., Van Meir, E. G., & Rutka, J. T. (2016). A role for activated Cdc42 in glioblastoma multiforme invasion. Oncotarget, 7(35), 56958–56975.
Weeks, A., Agnihotri, S., Lymer, J., Chalil, A., Diaz, R., Isik, S., Smith, C., & Rutka, J. T. (2016). Epithelial Cell Transforming 2 and Aurora Kinase B Modulate Formation of Stress Granule-Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells. The American Journal of Pathology, 186(6), 1674–1687.
2015
Diaz, R. J., Golbourn, B., Faria, C., Picard, D., Shih, D., Raynaud, D., Leadly, M., MacKenzie, D., Bryant, M., Bebenek, M., Smith, C. A., Taylor, M. D., Huang, A., & Rutka, J. T. (2015). Mechanism of action and therapeutic efficacy of Aurora kinase B inhibition in MYC overexpressing medulloblastoma. Oncotarget, 6(5), 3359–3374.
Faria, C. C., Agnihotri, S., Mack, S. C., Golbourn, B. J., Diaz, R. J., Olsen, S., Bryant, M., Bebenek, M., Wang, X., Bertrand, K. C., Kushida, M., Head, R., Clark, I., Dirks, P., Smith, C. A., Taylor, M. D., & Rutka, J. T. (2015). Identification of alsterpaullone as a novel small molecule inhibitor to target group 3 medulloblastoma. Oncotarget, 6(25), 21718–21729.
Faria, C. C., Golbourn, B. J., Dubuc, A. M., Remke, M., Diaz, R. J., Agnihotri, S., Luck, A., Sabha, N., Olsen, S., Wu, X., Garzia, L., Ramaswamy, V., Mack, S. C., Wang, X., Leadley, M., Reynaud, D., Ermini, L., Post, M., Northcott, P. A., … Rutka, J. T. (2015). Foretinib is effective therapy for metastatic sonic hedgehog medulloblastoma. Cancer Research, 75(1), 134–146.
2014
Diaz, R. J., McVeigh, P. Z., O’Reilly, M. A., Burrell, K., Bebenek, M., Smith, C., Etame, A. B., Zadeh, G., Hynynen, K., Wilson, B. C., & Rutka, J. T. (2014). Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors. Nanomedicine: Nanotechnology, Biology, and Medicine, 10(5), 1075–1087.
Okura, H., Smith, C. A., & Rutka, J. T. (2014). Gene therapy for malignant glioma. Molecular and Cellular Therapies, 2, 21.
Park, J.-B., Agnihotri, S., Golbourn, B., Bertrand, K. C., Luck, A., Sabha, N., Smith, C. A., Byron, S., Zadeh, G., Croul, S., Berens, M., & Rutka, J. T. (2014). Transcriptional profiling of GBM invasion genes identifies effective inhibitors of the LIM kinase-Cofilin pathway. Oncotarget, 5(19), 9382–9395.
2013
Terakawa, Y., Agnihotri, S., Golbourn, B., Nadi, M., Sabha, N., Smith, C. A., Croul, S. E., & Rutka, J. T. (2013). The role of drebrin in glioma migration and invasion. Experimental Cell Research, 319(4), 517–528.
2012
Diaz, R. J., Golbourn, B., Shekarforoush, M., Smith, C. A., & Rutka, J. T. (2012). Aurora kinase B/C inhibition impairs malignant glioma growth in vivo. Journal of Neuro-Oncology, 108(3), 349–360.
Diaz, R. J., Guduk, M., Romagnuolo, R., Smith, C. A., Northcott, P., Shih, D., Berisha, F., Flanagan, A., Munoz, D. G., Cusimano, M. D., Pamir, M. N., & Rutka, J. T. (2012). High-resolution whole-genome analysis of skull base chordomas implicates FHIT loss in chordoma pathogenesis. Neoplasia (New York, N.Y.), 14(9), 788–798.
Etame, A. B., Diaz, R. J., O’Reilly, M. A., Smith, C. A., Mainprize, T. G., Hynynen, K., & Rutka, J. T. (2012). Enhanced delivery of gold nanoparticles with therapeutic potential into the brain using MRI-guided focused ultrasound. Nanomedicine: Nanotechnology, Biology, and Medicine, 8(7), 1133–1142.
Etame, A. B., Diaz, R. J., Smith, C. A., Mainprize, T. G., Hynynen, K., & Rutka, J. T. (2012). Focused ultrasound disruption of the blood-brain barrier: A new frontier for therapeutic delivery in molecular neurooncology. Neurosurgical Focus, 32(1), E3.
Weeks, A., Okolowsky, N., Golbourn, B., Ivanchuk, S., Smith, C., & Rutka, J. T. (2012). ECT2 and RASAL2 mediate mesenchymal-amoeboid transition in human astrocytoma cells. The American Journal of Pathology, 181(2), 662–674.
Seol, H. J., Chang, J. H., Yamamoto, J., Romagnuolo, R., Suh, Y., Weeks, A., Agnihotri, S., Smith, C. A., & Rutka, J. T. (2012). Overexpression of CD99 Increases the Migration and Invasiveness of Human Malignant Glioma Cells. Genes & Cancer, 3(9–10), 535–549.
2011
Etame, A. B., Smith, C. A., Chan, W. C. W., & Rutka, J. T. (2011). Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature. Nanomedicine: Nanotechnology, Biology, and Medicine, 7(6), 992–1000.
Faria, C. M. C., Rutka, J. T., Smith, C., & Kongkham, P. (2011). Epigenetic mechanisms regulating neural development and pediatric brain tumor formation. Journal of Neurosurgery. Pediatrics, 8(2), 119–132.
Restrepo, A., Smith, C. A., Agnihotri, S., Shekarforoush, M., Kongkham, P. N., Seol, H. J., Northcott, P., & Rutka, J. T. (2011). Epigenetic regulation of glial fibrillary acidic protein by DNA methylation in human malignant gliomas. Neuro-Oncology, 13(1), 42–50.
2010
Nakahara, Y., Northcott, P. A., Li, M., Kongkham, P. N., Smith, C., Yan, H., Croul, S., Ra, Y.-S., Eberhart, C., Huang, A., Bigner, D., Grajkowska, W., Van Meter, T., Rutka, J. T., & Taylor, M. D. (2010). Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia (New York, N.Y.), 12(1), 20–27.
Kongkham, P. N., Northcott, P. A., Croul, S. E., Smith, C. A., Taylor, M. D., & Rutka, J. T. (2010). The SFRP family of WNT inhibitors function as novel tumor suppressor genes epigenetically silenced in medulloblastoma. Oncogene, 29(20), 3017–3024.
Kongkham, P. N., Onvani, S., Smith, C. A., & Rutka, J. T. (2010). Inhibition of the MET Receptor Tyrosine Kinase as a Novel Therapeutic Strategy in Medulloblastoma. Translational Oncology, 3(6), 336–343.
2009
Seol, H. J., Smith, C. A., Salhia, B., & Rutka, J. T. (2009). The Guanine Nucleotide Exchange Factor SWAP-70 Modulates the Migration and Invasiveness of Human Malignant Glioma Cells. Translational Oncology, 2(4), 300–309.
Osawa, H., Smith, C. A., Ra, Y. S., Kongkham, P., & Rutka, J. T. (2009). The role of the membrane cytoskeleton cross-linker ezrin in medulloblastoma cells. Neuro-Oncology, 11(4), 381–393.
2008
Salhia, B., Hwang, J. H., Smith, C. A., Nakada, M., Rutka, F., Symons, M., & Rutka, J. T. (2008). Role of myosin II activity and the regulation of myosin light chain phosphorylation in astrocytomas. Cell Motility and the Cytoskeleton, 65(1), 12–24.
Kongkham, P. N., Northcott, P. A., Ra, Y. S., Nakahara, Y., Mainprize, T. G., Croul, S. E., Smith, C. A., Taylor, M. D., & Rutka, J. T. (2008). An epigenetic genome-wide screen identifies SPINT2 as a novel tumor suppressor gene in pediatric medulloblastoma. Cancer Research, 68(23), 9945–9953.
