Vijay Ramaswamy

At a Glance

• Our overarching strategy is to leverage genomic profiling to identify new targets, and to evaluate these targets in faithful models, which would allow for proper combination testing of new agents/strategies.
• We use a combination of genomic and epigenetic strategies with integrative analyses to profile clinically annotated cohorts of primary pediatric brain tumours.  Our goal is to identify and validate prognostic, predictive and therapeutic biomarkers.
• Appropriate model systems are identified and/or generated where preclinical testing is performed, usually in combination with established therapies. Unbiased genome wide screening of pre-clinical models are also performed using a variety of techniques including siRNA and CRISPR/Cas9 and outputs are compared to primary human genomic data.
• We collaborate with groups globally where we aim to model biological heterogeneity of pediatric brain tumours, and leverage this heterogeneity to develop new targeted treatment approaches.
• We seek to identify mechanisms of treatment resistance and sensitization, particularly identification of new methods of radiosensitization in the treatment of high-risk pediatric brain brain tumours.

Short Bio

Dr. Vijay Ramaswamy is originally from Northern Alberta, where he completed medical school and a paediatric neurology residency at the University of Alberta (MD ’05, FRCPC ’10). Following that he completed a paediatric neuro-oncology fellowship at Memorial Sloan Kettering Cancer Center in New York, after which he came to Toronto where he completed a PhD in Cancer Genomics at the University of Toronto (PhD ’15) and a clinical neuro-oncology fellowship at The Hospital for Sick Children (SickKids). He is currently a staff neuro-oncologist in the Paediatric Brain Tumour Program at SickKids, holds a Canada Research Chair in Pediatric Neuro-Oncology and is a Scientist within the Developmental and Stem Cell Biology Program at the Hospital for Sick Children Research Institute. His research interests primarily involve translational genomics of both medulloblastoma and ependymoma with a specific interest in recurrent and high-risk tumours.

Research Synopsis

Molecular classification and novel target identification in ependymoma

Through an integrated genomic analyses of high risk pediatric brain tumours we seek to establish robust molecular classifications, define molecular landscapes and identify putative new targets for therapy.  Clinically annotated cohorts and clinical trial specimens are being preferentially used to provide clinical correlates to molecular findings. We leverage this genomic data to identify new targets for therapy which we validate in representative model systems. In parallel we leverage unbiased screening to correlate with human molecular datasets.

Mechanisms to overcome radioresistance in pediatric brain tumours

Radiation therapy is the mainstay of treatment for the majority of children with pediatric brain tumours.  Using both in vitro and in vivo approaches, we seek to identify mechanisms of treatment resistance, primarily radiation resistance. Synthetic lethal approaches are employed to identify vulnerabilities in response to DNA damage, which may allow us to identify new and novel radiosensitizers.

Funding

• Canadian Institutes of Health Research
• Canadian Cancer Society Research Institute
• Canada Research Chairs
• Brain Canada
• Rally Foundation
• Matthew Larson Foundation
• American Brain Tumor Association
• Brain Tumour Foundation of Canada
• Meagan’s Hug
• b.r.a.i.n.child
• Garron Family Cancer Center
• Stand Up to Cancer

Recent Publications

• Coltin H, Pequeno P, Liu N, Tsang DS, Gupta S, Taylor MD, Bouffet E, Nathan PC, Ramaswamy V. The burden of surviving childhood medulloblastoma: a population-based, matched cohort study in Ontario, Canada.  J Clin Oncol (in press)
• Kumar R, Smith KS, Deng M, Terhune C, Robinson GW, Orr BA, Liu APY, Lin T, Billups CA, Chintagumpala M, Bowers DC, Hassall TE, Hansford JR, Khuong-Quang DA, Crawford JR, Bendel AE, Gururangan S, Schroeder K, Bouffet E, Bartels U, Fisher MJ, Cohn R, Partap S, Kellie SJ, McCowage G, Paulino AC, Rutkowski S, Fleischhack G, Dhall G, Klesse LJ, Leary S, Nazarian J, Kool M, Wesseling P, Ryzhova M, Zheludkova O, Golanov AV, McLendon RE, Packer RJ, Dunham C, Hukin J, Fouladi M, Faria CC, Pimentel J, Walter AW, Jabado N, Cho YJ, Perreault S, Croul SE, Zapotocky M, Hawkins C, Tabori U, Taylor MD, Pfister SM, Klimo P, Jr., Boop FA, Ellison DW, Merchant TE, Onar-Thomas A, Korshunov A, Jones DTW, Gajjar A, Ramaswamy V*, Northcott PA*. Clinical Outcomes and Patient-Matched Molecular Composition of Relapsed Medulloblastoma. J Clin Oncol. 2021 Mar 1;39(7):807-21. PubMed PMID: 33502920. Pubmed Central PMCID: PMC8078396. Epub 2021/01/28. eng. *denotes co-senior authors
• Nobre L, Zapotocky M, Khan S, Fukuoka K, Fonseca A, McKeown T, Sumerauer D, Vicha A, Grajkowska WA, Trubicka J, Li KKW, Ng HK, Massimi L, Lee JY, Kim SK, Zelcer S, Vasiljevic A, Faure-Conter C, Hauser P, Lach B, van Veelen-Vincent ML, French PJ, Van Meir EG, Weiss WA, Gupta N, Pollack IF, Hamilton RL, Nageswara Rao AA, Giannini C, Rubin JB, Moore AS, Chambless LB, Vibhakar R, Ra YS, Massimino M, McLendon RE, Wheeler H, Zollo M, Ferruci V, Kumabe T, Faria CC, Sterba J, Jung S, Lopez-Aguilar E, Mora J, Carlotti CG, Olson JM, Leary S, Cain J, Krskova L, Zamecnik J, Hawkins CE, Tabori U, Huang A, Bartels U, Northcott PA, Taylor MD, Yip S, Hansford JR, Bouffet E, Ramaswamy V. Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma. Cell Rep Med. 2020 Jun 23;1(3). PubMed PMID: 32743560. Pubmed Central PMCID: PMC7394286. Epub 2020/08/04. eng.
• Baroni L, Sundaresan L, Heled A, Coltin H, Pajtler KW, Lin T, Merchant TE, McLendon R, Faria C, Buntine M, White CL, Pfister SM, Gilbert MR, Armstrong TS, Bouffet E, Kumar S, Taylor MD, Aldape KD, Ellison DW, Gottardo NG, Kool M, Korshunov A, Hansford JR, Ramaswamy V. Ultra high-risk PFA ependymoma is characterized by loss of chromosome 6q. Neuro Oncol. 2021 Aug 2;23(8):1360-1370.
• Merchant TE, Bendel AE, Sabin ND, Burger PC, Shaw DW, Chang E, Wu S, Zhou T, Eisenstat DD, Foreman NK, Fuller CE, Anderson ET, Hukin J, Lau CC, Pollack IF, Laningham FH, Lustig RH, Armstrong FD, Handler MH, Williams-Hughes C, Kessel S, Kocak M, Ellison DW, Ramaswamy V. Conformal Radiation Therapy for Pediatric Ependymoma, Chemotherapy for Incompletely Resected Ependymoma, and Observation for Completely Resected, Supratentorial Ependymoma. J Clin Oncol. 2019 Feb 27:JCO1801765. doi: 10.1200/JCO.18.01765. [Epub ahead of print]
• Cavalli FMG, Hübner JM, Sharma T, Luu B, Sill M, Zapotocky M, Mack SC, Witt H, Lin T, Shih DJH, Ho B, Santi M, Emery L, Hukin J, Dunham C, McLendon RE, Lipp ES, Gururangan S, Grossbach A, French P, Kros JM, van Veelen MC, Rao AAN, Giannini C, Leary S, Jung S, Faria CC, Mora J, Schüller U, Alonso MM, Chan JA, Klekner A, Chambless LB, Hwang EI, Massimino M, Eberhart CG, Karajannis MA, Lu B, Liau LM, Zollo M, Ferrucci V, Carlotti C, Tirapelli DPC, Tabori U, Bouffet E, Ryzhova M, Ellison DW, Merchant TE, Gilbert MR, Armstrong TS, Korshunov A, Pfister SM, Taylor MD, Aldape K, Pajtler KW, Kool M, Ramaswamy V. Heterogeneity within the PF-EPN-B ependymoma subgroup. Acta Neuropathologica. 136:227-237 (2018). doi: 10.1007/s00401-018-1888-x.
• Liang L, Morrison LC, Tatari N, Stromecki M, Fresnoza A, Porter CJ, Del Bigio MR, Hawkins C, Chan JA, Ryken TC, Taylor MD, Ramaswamy V*, Werbowetski-Ogilvie TE*. CD271+ cells are diagnostic and prognostic and exhibit elevated MAPK activity in SHH medulloblastoma. Cancer Res. 78:4745-4759 (2018). PubMed PMID: 29930101. *co-senior and co-corresponding authors.
• Cavalli FMG, Remke M, Rampasek L, … Goldenberg A*, Ramaswamy V*, Taylor MD*. Intertumoral Heterogeneity within Medulloblastoma Subgroups. Cancer Cell. 2017 Jun 12;31(6):737-754.e6. doi: 10.1016/j.ccell.2017.05.005. PubMed PMID: 28609654. *co-senior and co-corresponding author.
• Ramaswamy V, Hielscher T, Mack SC, Taylor MD. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era. Journal of Clinical Oncology. 34:2468-77 (2016).
• Ramaswamy V, Remke M, Bouffet E, Bailey S, Clifford SC, Doz F, Kool M, Dufour C, Vassal G, Milde T, Witt O, von Hoff K, Pietsch T, Northcott PA, Gajjar A, Robinson GW, Padovani L, André N, Massimino M, Pizer B, Packer R, Rutkowski S, Pfister SM, Taylor MD, Pomeroy SL. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathologica. 131:821-31. (2016) *Corresponding Author.
• Ramaswamy V, Remke M, Bouffet E, Taylor MD. Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14:1200-1207. (2013)
• Thompson E, Hielscher T, Bouffet E. Ramaswamy V*, Taylor MD*. Prognostic value of medulloblastoma extent of resection after accounting for molecular subgroup: An intergrated clinical and molecular analysis. Lancet Oncol 2016 17:484-495. *Co-Senior Authors

Graduate Students

Alexandria Decarlo
Julija Povilaikaite
Alexandra Riemenschneider