The overall premise of my research is that a greater understanding of how childhood cancer cells respond to extra- or intracellular signals is necessary to identify tumour-specific pathways. Only then can these pathways be targeted therapeutically in a manner that minimizes effects on normal cells. This is especially important in childhood cancer to avoid toxic effects of treatments on the intellectual, physical, and emotional development of a growing child. An ongoing difficulty with this approach is how to find the relevant pathways to target. Over the years, we have chosen to characterize recurrent genetic alterations in childhood tumours as a means to more efficiently identify novel cancer genes. This is part of our belief that analysis of primary tumours is preferable for initial identification of pathophysiologically relevant alterations in human malignancies. With the advent of next-generation sequencing, we are now extending this approach to whole genome sequencing of childhood cancers to better understand the mutational landscape of these tumours. Then, once the involved proteins have been identified, model systems can be invoked to further study their biology and how the pathways they are involved in become activated. We then use various biochemical approaches as well as high-throughput platforms such as RNA interference screening to rigorously characterize the involved proteins, their functional interactors, and the signal transduction pathways they participate in. This forms the basis for subsequent strategies to therapeutically target candidate proteins in childhood cancers.

Full list of publications may be found here.

Members

Faculty/Leaders

Affiliate

Philipp Lange

Affiliated Scientist

Staff

Cynthia Ferguson

Research Projects and Operations Leader

Yue Zhou (Joe) Huang

Research Assistant / Technician

Christopher Hughes

Mass Spectrometry Service Specialist

Michael Lizardo

Staff Scientist

Melanie Rouleau

Research Project Manager

Xiaqiu Yang

Research Assistant/Technician

Post-Docs

Alberto Delaidelli

Postdoctoral Fellow

Anne-Chloe Dhez

Post-doctoral Fellow

Ashish Kumar

Postdoctoral Fellow

Renata Scopim Ribeiro

Post-doctoral Fellow

Students/Trainees

Fares Burwag

Co-op Student

Aditya Chauhan

Directed studies student

Mariam Hassan

Directed studies student

Sofya Langman

Graduate Student

Jessica Oliveira de Santis

Visiting Student

Manideep Chowdary Pachva

Graduate Student

Ella Poynton

Co-op Student

Taras Shyp

Graduate Student

Busra Turgu

Graduate Student

Selected Publications

Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma.

Cancer discovery, 2021
Zhang, Hai-Feng, Hughes, Christopher S, Li, Wei, He, Jian-Zhong, Surdez, Didier, El-Naggar, Amal M, Cheng, Hongwei, Prudova, Anna, Delaidelli, Alberto, Negri, Gian Luca, Li, Xiaojun, Ørum-Madsen, Maj Sofie, Lizardo, Michael M, Oo, Htoo Zarni, Colborne, Shane, Shyp, Taras, Scopim-Ribeiro, Renata, Hammond, Colin A, Dhez, Anne-Chloe, Langman, Sofya, Lim, Jonathan K M, Kung, Sonia H Y, Li, Amy, Steino, Anne, Daugaard, Mads, Parker, Seth J, Geltink, Ramon I Klein, Orentas, Rimas J, Xu, Li-Yan, Morin, Gregg B, Delattre, Olivier, Dimitrov, Dimiter S, Sorensen, Poul H

Class I HDAC inhibitors enhance YB-1 acetylation and oxidative stress to block sarcoma metastasis.

EMBO reports, 2019
El-Naggar, Amal M, Somasekharan, Syam Prakash, Wang, Yemin, Cheng, Hongwei, Negri, Gian Luca, Pan, Melvin, Wang, Xue Qi, Delaidelli, Alberto, Rafn, Bo, Cran, Jordan, Zhang, Fan, Zhang, Haifeng, Colborne, Shane, Gleave, Martin, Mandinova, Anna, Kedersha, Nancy, Hughes, Christopher S, Surdez, Didier, Delattre, Olivier, Wang, Yuzhuo, Huntsman, David G, Morin, Gregg B, Sorensen, Poul H

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein.

Cancer cell, 2015
Salanti, Ali, Clausen, Thomas M, Agerbæk, Mette Ø, Al Nakouzi, Nader, Dahlbäck, Madeleine, Oo, Htoo Zarni, Lee, Sherry, Gustavsson, Tobias, Rich, Jamie R, Hedberg, Bradley J, Mao, Yang, Barington, Line, Pereira, Marina A, LoBello, Janine, Endo, Makoto, Fazli, Ladan, Soden, Jo, Wang, Chris K, Sander, Adam F, Dagil, Robert, Thrane, Susan, Holst, Peter J, Meng, Le, Favero, Francesco, Weiss, Glen J, Nielsen, Morten A, Freeth, Jim, Nielsen, Torsten O, Zaia, Joseph, Tran, Nhan L, Trent, Jeff, Babcook, John S, Theander, Thor G, Sorensen, Poul H, Daugaard, Mads

Translational Activation of HIF1α by YB-1 Promotes Sarcoma Metastasis.

Cancer cell, 2015
El-Naggar, Amal M, Veinotte, Chansey J, Cheng, Hongwei, Grunewald, Thomas G P, Negri, Gian Luca, Somasekharan, Syam Prakash, Corkery, Dale P, Tirode, Franck, Mathers, Joan, Khan, Debjit, Kyle, Alastair H, Baker, Jennifer H, LePard, Nancy E, McKinney, Steven, Hajee, Shamil, Bosiljcic, Momir, Leprivier, Gabriel, Tognon, Cristina E, Minchinton, Andrew I, Bennewith, Kevin L, Delattre, Olivier, Wang, Yuzhuo, Dellaire, Graham, Berman, Jason N, Sorensen, Poul H

The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation.

Cell, 2013
Leprivier, Gabriel, Remke, Marc, Rotblat, Barak, Dubuc, Adrian, Mateo, Abigail-Rachele F, Kool, Marcel, Agnihotri, Sameer, El-Naggar, Amal, Yu, Bin, Somasekharan, Syam Prakash, Faubert, Brandon, Bridon, Gaëlle, Tognon, Cristina E, Mathers, Joan, Thomas, Ryan, Li, Amy, Barokas, Adi, Kwok, Brian, Bowden, Mary, Smith, Stephanie, Wu, Xiaochong, Korshunov, Andrey, Hielscher, Thomas, Northcott, Paul A, Galpin, Jason D, Ahern, Christopher A, Wang, Ye, McCabe, Martin G, Collins, V Peter, Jones, Russell G, Pollak, Michael, Delattre, Olivier, Gleave, Martin E, Jan, Eric, Pfister, Stefan M, Proud, Christopher G, Derry, W Brent, Taylor, Michael D, Sorensen, Poul H

Projects

Discovery and Development of Optimal Immunotherapeutic Strategies for Childhood Cancers

High-risk pediatric cancers remain the leading cause of mortality in childhood, and current standard approaches to treat pediatric cancers frequently induce unacceptable life-long morbidity. This multi-center collaborative effort focuses on identifying and understanding the fundamental mechanisms leading to high-risk childhood cancers, including how these malignancies evolve to evade the immune system and resist modern therapies.

Sponsors

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