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Michael D. Taylor

Picture of Dr. Michael D Taylor

Professor

MD, PhD, University of Toronto

The Hospital for Sick Children
Peter Gilgan Centre for Research and Learning (PGCRL)
686 Bay Street, 17.9410-E-West
Toronto, ON M5G 0A4
Lab Phone: 416-813-7654 X301543
Email: Dr. Michael Taylor
Lab website: http://www.sickkids.ca/Research/Taylor-lab/

At A Glance:

  • Research focuses on the study of paediatric brain tumours — specifically Medulloblastoma and Ependymoma
  • Using functional genomic and epigenomic tools to investigate how normal cells are turned into brain tumours
  • Developing new animal and cell culture models for identification and targeting of novel cancer biomarkers
  • A multi-layered translational research approach to allow for rapid clinically-important changes to brain tumour therapy, such that the quality of life of patients can be drastically improved.

 

Short Bio:

Dr. Taylor joined the Division of Neurosurgery at the Hospital for Sick Children (SickKids) in 2004, he is a Professor of Surgery, Medical Biophysics and Laboratory Medicine and Pathobiology at the University of Toronto, and a Senior Scientist in the Developmental and Stem Cell Biology Program at the SickKids Research Institute. He was previously awarded the Gold medal in Surgery from the Royal College of Physicians and Surgeons of Canada, the Canadian Cancer Society Award for Excellence in Cancer Research, Canada's Top 40 under 40, and the Zulch Prize in Basic Neuroscience Research. He is a Garron Family Chair for Childhood Cancer Research at the Hospital for Sick Children.  Dr. Taylor has extensive peer reviewed funding from the CIHR, The Canadian Cancer Society, The Terry Fox Research Institute, Stand Up 2 Cancer, The V Foundation, World Wide Cancer Research, The National Institutes of Health (USA), the Ontario Institute for Cancer Research, and Genome Canada.  Dr. Taylor’s research focuses on childhood brain tumors, particularly medulloblastoma and ependymoma.  He has published over 280 peer reviewed publications, with publications in high impact journals such as Nature, Cell, Cancer Cell, and Nature Genetics.  His publications have been cited >24,000 times and many former graduate students and post-doctoral fellows from the Taylor Lab have gone on to lead their own independent research groups at prestigious universities around the world.

Major Contributions:

Work from Dr. Taylor’s lab has significantly impacted health care and advanced the treatment of brain tumours for children in Canada and around the world. Highlights of recent contributions include:

1) Discovery that Medulloblastoma is a Heterogeneous Entity Comprised of Distinct Diseases
Taylor et al. Acta Neuropathologica 2012, PMID 22134537, Shih et al. Journal of Clinical Oncology 2014, PMID:24493713, Ramaswamy et al. Neuro-Oncology 2015, PMID: 25605817, Cavalli and Remke et al. Cancer Cell 2017, PMID:28609654.

Medulloblastoma had been considered to comprise one heterogeneous entity diagnosed using the light microscope.  The Taylor Lab demonstrated, and it is now accepted by a global consensus that medulloblastoma is in fact comprised of at least four distinct diseases, each with their own epidemiology, demographics, genetics, transcriptomics, and response to therapy.  Clinical trials across the globe both account for, and stratify patients based on this classification. Subgroup affiliation determined in the SickKids CLIA lab is now part of the standard of care for medulloblastoma patients at SickKids.

2) Discovery of Novel Medulloblastoma Oncogenes and Tumour Suppressor Genes.
Northcott et al. Nature 2012. PMID: 22832581. Huang et al. Nature Neuroscience 2015 PMID: 26258683.

The Taylor Lab described and characterized a number of somatic and germline mutations that are drivers in subgroups of medulloblastoma.  These driver events are useful for modeling the disease, and as targets for rational therapy.

3) Discovery of molecular distinct subgroups of ependymoma brain tumors from different parts of the central nervous system that are biologically distinct, likely arise from radial glial cell progenitor cells. 
Northcott et al. Nature 2012. PMID: 22832581. Northcott et al. Nature Genetics 2009. PMID: 1927076. Taylor et al. Nature Genetics 2002. PMID: 12068298. Huang et al. Nature Neuroscience 2015 PMID: 26258683.

Ependymoma can arise at all levels of the nervous system, and was thought to arise from post-mitotic cells of the ependymal.  The Taylor Lab have shown that in fact, ependymomas arise from radial glial cells (CNS progenitors), and that there are several distinct molecular subgroups of ependymoma with widely variant biology and outcomes.  The next round of clinical trials for ependymoma are all accounting for these molecular subgroups.

4.) Discovery of clinically significant heterogeneity in metastatic/recurrent medulloblastoma and unearthing haemotageounous dissemination of metastatic disease.
Wu et al. Nature 2012. PMID: 22343890. Ramaswamy et al. Lancet Oncology 2013. PMID: 24140199. Wang et al. Acta Neuropathologica 2015. PMID: 25689980. Garzia et al. Nature 2016, PMID: 26760213. Morrissy et al., Nature Genetics 2017, PMID: 28394352. Garzia et al., Cell 2018, PMID:29474906

Current modus operandi are to discover and validate novel targets for therapy on untreated primary tumors, and then to take novel agents to clinical trials and test them on patients with highly treated, recurrent, metastatic disease.  This approach is doomed to failure, as the Taylor Lab have shown that children die from metastases rather than the primary tumor, that metastases are vastly different from the primary tumor, and that recurrent disease has undergone extensive clonal divergence from the untreated primary tumor.  These findings necessitate re-biopsy at recurrence for targeted therapy, and considering temporal and spatial heterogeneity when studying medulloblastoma to develop novel therapies. Despite the previous notion that medulloblastoma CNS metastases occur via local seeding of the spinal cord, the Taylor Lab recently published evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrated in vivo, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form metastases.

5.) Discovery and delineation of the importance of epigenetic mechanisms in childhood brain tumors.
Mack et al. Nature 2014. PMID: 24553142.  Hovestadt et al. Nature 2014. PMID: 24847876. Leprivier et al. Cell 2013. PMID: 23706743.  Dubuc et al. Acta Neuropathologica 2013. PMID: 23184418. Mack et al. Nature 2017. PMID: 29258295.

Both medulloblastoma and ependymoma have a paucity of recurrent somatic mutations, particularly SNVs.  Due to a lack of somatic genetic targets, alternatives must be found.  The Taylor Lab have shown in a number of publications that non-genetic, particularly epigenetic mechanisms (both DNA CpG methylation and histone post-translational modifications) are important in medulloblastoma and ependymoma biology, and might serve as novel targets for rational therapy.

Google Scholar Profile: https://scholar.google.ca/citations?user=5Od-c5QAAAAJ&hl=en

List of Key Publications:

Link to full publication list

1) Garzia L, Kijima N, Morrissey AS, De Antonellis P, Guerreiro-Stucklin A, Holgado BL, Wu X, Wang X, Parsons M, Zayne K, Manno A, Kuzan-Fisher C, Nor C, Donovan LK, Lui J, Qin L, Garancher A, Liu KW, Mansouri S, Luu B, Thompson YY, Ramaswamy V, Peacock J, Farooq H, Skowron P, Shih DJH, Li A, Ensan S, Robbins CS, Cybulsky M, Mitra S, Ma Y, Moore R, Mungall A, Cho YJ, Weiss WA, Chan JA, Hawkins CE, Massimino M, Jabado N, Zapatocky M, Sumeraurer D, Bouffet E, Dirks P, Tabori U, Sorenson PHB, Brastianos PK, Aldape K, Jones SJM, Marra MA, Woodgett JR, Wechsler-Reya RJ, Fults DW, Taylor MD.  A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases. Cell. 2018 Feb 22;172(5):1050-1062.e14 (PMID: 29474906)

2) Mack SC, Pajtler KW, Chavez L, Okonechnikov K, Bertrand KC, Wang X, Erkek S, Federation A, Song A, Lee C, Wang X, McDonald L, Morrow JJ, Saiakhova A, Sin-Chan P, Wu Q, Michaelraj KA, Miller TE, Hubert CG, Ryzhova M, Garzia L, Donovan L, Dombrowski S, Factor DC, Luu B, Valentim CLL, Gimple RC, Morton A, Kim L, Prager BC, Lee JJY, Wu X, Zuccaro J, Thompson Y, Holgado BL, Reimand J, Ke SQ, Tropper A, Lai S, Vijayarajah S, Doan S, Mahadev V, Minan AF, Grobner SN, Liehard M, Zapatka M, Huang Z, Aldape KD, Carcaboso AM, Houghton PJ, Keir ST, Milde T, Witt H, Li Y, Li CJ, Bian XW, Jones DTW, Scott I, Singh SK, Huang A, Dirks PB, Bouffet E, Bradner JE, Ramaswamy V, Jabado N, Rutka JT, Northcott PA, Lupien M, Lichter P, Korshunov A, Scacheri P, Pfister SM, Kool M, Taylor MD, Rich JN.  Therapeutic targeting of ependymoma as informed by enhancer profiling.  Nature. 2018 Jan 4;553(7686):101-105 (PMID:29258295)

3) Cavalli FMG, Remke M, Rampasek L, Peacock J, Shih DJH, Luu B, Garzia L, Torchia J, Nor C, Morrissy AS, Agnihotri AS, Thompson YY, Kuzan-Fischer CM, Farooq H, Isaev K, Daniels C, Cho BK, Kim SK, Wang KC, Lee JY, Grajkowska WA, Perek-Polnik M, Vasiljevic A, Faure-Conter C, Jouvet A, Giannini C, Nageswara Rao AA, Li KKW, Ng HK, Eberhart CG, Pollack IF, Hamilton RL, Gillespie GY, Olson JM, Leary S, Weiss WA, Lach B, Chambless LB, Thompson RC, Cooper MK, Vibhaker R, Hauser P, van Veelen MC, Kros JM, French PJ, Ra YS, Kumabe T, Lopez-Aguilar E, Zitterbart K, Sterba J, Finocchiaro G, Massimino M, Van Meir EG, Osuka S, Shofuda T, Klekner A, Zollo M, Leonard JR, Rubin JB, Jabado N, Albrecht S, Mora J, Van Meter TE, Jung S, Morre AS, Hallahan AR, Chan JA, Tirapelli DPC, Carlotti CG, Fouladi M, Pimental J, Faria CC, Saad AG, Massimi L, Liau LM, Wheeler H, Nakamura H, Elbabaa SK, Perezpena-Diazconti M, Chico Ponce de Leon, Robinson S, Zapotocky M, Lassaletta A, Huang A, Hawkins CE, Tabori U, Bouffet E, Bartels U, Dirks PB, Rutka JT, Bader GD, Reimand J, Goldenberg A, Ramaswamy V, Taylor MD. Intertumoral Heterogeneity within Medulloblastoma Subgroups.  Cancer Cell. 2017 Jun 12;31(6):737-754.e6 (PMID:28609654)

4) Morrissy AS, Cavalli FMG, Remke M, Ramaswamy V, Shih DJH, Holgado BL, Farooq H, Donovan LK, Garzia L, Agnihotri S, Kiehna EN, Mercier E, Mayoh C, Papillion-Cavanagh S, Nikbakht H, Gaydin T, Torchia J, Picard D, Merino DM, Luu B, Wu X, Horswell S, Thompson YY, Hovestadt V, Northcott PA, Jones DTW, Peacock J, Wang X, Mack SC, Reimand J, Albrecht S, Fontebasso A, Thiessen N, Li Y, Schein JE, Lee D, Carlsen R, Mayo M, Tse K, Tam A, Dhala N, Ally A, Chuah E, Cheng Y, Plettner P, Li HI, Corbett RD, Wong T, Long W, Loukides J, Buczkowicz P, Hawkins CE, Tabori U, Rood BR, Myseros JS, Packer RJ, Korshunov A, Lichter P, Kool M, Pfister SM, Schuller U, Dirks P, Huang A, Bouffet E, Rutka JT, Bader GD, Swanton C, Ma Y, Moore RA, Mungall AJ, Majewski J, Jones SJM, Das S, Malkin D, Jabado N, Marra MA, Taylor MD. Spatial Heterogeneity in medulloblastoma.  Nat Genet. 2017 May;49(5):780-788 (PMID:28394352)

5) Thompson EM, Hielscher T, Bouffet E, Remke M, Luu B, Gururangan S, McLendon RE, Bigner DD, Lipp ES, Perreault S, Cho YJ, Grant G, Kim SK, Lee JY, Rao AAN, Giannini C, Li KKW, Ng HK, Yao Y, Kumabe T, Tominaga T, Grajkowska WA, Perek-Polnik M, Low CDY, Seow WT, Chang KTE, Mora J, Pollack IF, Hamilton RL, Leary S, Moore AS, Ingram WJ, Hallahan AR, Jouvet A, Fevre-Montagne M, Vasiljevic A, Faure-Conter C, Shofuda T, Kagawa N, Hashimoto N, Jabado N, Weill AG, Gayden T, Wataya T, Shalaby T, Grotzer M, Zitterbart K, Sterb J, Kren L, Hortobagyi T, Klekner A, Laszlo B, Pocza T, Hauser P, Schuller U, Jung Jang WY, French PJ, Kros JM, van Veelan MLC, Massimi L, Leonard JR, Rubin JB, Vibhaker R, Chambless LB, Cooper MK, Thompson RC, Faria CC, Carvalho A, Nunes S, Pimental J, Fan X, Muraszko KM, Lopez-Aguilar E, Lyden D, Garzia L, Shih DJH, Kijima N, Schneider C, Adamski J, Northcott PA, Kool M, Jones DTW, Chan JA, Nikolic A, Garre ML, Van Meir EG, Osuka JJ, Jahangiri A, Castro BA, Gupta N, Weiss WA, Moxon-Emre I, Mabbott DJ, Lassaletta A, Hawkins CE, Tabori U, Drake J, Kulkarni A, Dirks P, Rutka JT, Korshunov A, Pfister SM, Packer RJ, Ramaswamy V, Taylor MD. Prognostic Value of medulloblastoma extent of resection after accounting for molecular subgroup in paediatric patients: a retrospective integrated clinical and molecular analysis.  Lancet Oncology 2016. 17(4): 484-95 (PMID:26976201)

6) Morrissy AS, Garzia L, Shih DJH, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli FMG, Ramaswamy V, Lindsay P, Jelveh S, Donovan LK, Wang X, Luu B, Zayne K, Li Y, Mayoh C, Thiessen N, Mercier E, Mungall KL, Yusanne M, Tse K, Zeng T, Shumansky K, Roth AJL, Shah S, Farooq H, Kijima N, Holgado BL, Lee JJY, Matan-Lithwick S, Liu J, Mack SC, Manno A, Michaelraj KA, Nor C, Peacock J, Qin L, Reimand J, Rolider A, Thompson YY, Wu X, Pugh T, Ally A, Bilenky M, Butterfied YSN, Carlsen R, Cheng Y, Chuah E, Corbett RD, Dhalla N, He A, Lee D, Li HI, Long W, Mayo M, Plettner P, Qian JQ, Schein JE, Tam A, Wong T, Birol I, Zhao Y, Faria CC, Pimentel J, Bendel AE, Fults DW, Walter AW, Kumabe T, Tominaga T, Collins VP, Cho YJ, Hoffman C, Lyden D, Wisoff J, Garvin JH, Stearns DS, Massimi L, Schuller U, Sterba J, Zitterbart K, Puget S, Ayrault O, Dunn SE, Tirapelli DPC, Carlotti CG, Wheeler H, Hallahan AR, Ingram W, MacDonald TJ, Olson JJ, Van Meir EG, Lee JY, Wang KC, Kim SK, Cho BK, Pietsch T, Fleischack G, Tippelt S, Ra YS, Bailey S, Lindsay JC, Clifford SC, Eberhart CG, Cooper MK, Packer R, Massimino M, Garre ML, Bartels U, Tabori U, Hawkins C, Dirks P, Bouffet E, Rutka JT, Wechsler-Reya RJ, Weiss WA, Collier LS, Dupuy AJ, Korshunov A, Jones DTW, Kool M, Northcott PA, Pfister SM, Largaespada DA, Mungall AJ, Moore RA, Jabadao N, Bader GD, Jones JM, Malkin D, Marra MA. Taylor MD.  Divergent Clonal Selection Drives Medulloblastoma at Recurrence.  Nature 2016. 529(7586): 351-7 (PMID:22343890)

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