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Paul A. Northcott, PhD
Paul A. Northcott, PhD

Paul A. Northcott, PhD

Member, St. Jude Faculty

  • Director, Center of Excellence for Neuro-Oncology Sciences (CENOS)
  • Endowed Chair, Molecular Neuro-Oncology

Departments

Education

BSc – Palm Beach Atlantic University, Florida
MSc – McMaster University, Ontario, Canada
PhD – University of Toronto, Ontario, Canada
Postdoctoral – The Hospital for Sick Children, Ontario, Canada
Postdoctoral – German Cancer Research Center (DKFZ), Heidelberg, Germany

Honors & Awards

  • 2024 Mark Foundation Emerging Leader Award 
  • 2020 St. Baldrick’s Foundation Robert J. Arceci Innovation Award
  • 2016 Sontag Foundation Distinguished Scientist Award
  • 2016 AACR NextGen Grant for Transformative Cancer Research
  • 2016 Pew-Stewart Scholar (Pew Charitable Trusts) 
  • 2015 V Foundation V Scholar Award
  • 2014 Pediatric Basic Science Award (Society for Neuro-Oncology (SNO) Meeting)
  • 2014 German Cancer Research Center (DKFZ) Alumni Award
  • 2013 Lap-Chee Tsui Publication Award for 2012 (CIHR Institute of Genetics)
  • 2012 Roman Herzog PostDoctoral Fellowship (Hertie Foundation)
  • 2011 Stuart Alan Hoffman Memorial Prize (University of Toronto)
  • 2011 Keystone Symposia Future of Science Fund Scholarship (Changing Landscape of the Cancer Genome Meeting)
  • 2010 Young Investigator Award (Basic Science Canadian Neuro-Oncology (CNO) Meeting)

Research Interests

  • Embryonal central nervous system tumors
  • Disrupted neurodevelopment in pediatric brain tumors
  • Genetic dependencies and preclinical model development
  • Liquid biopsy genetic and methylation signatures 

My research is focused on defining the molecular, cellular, and mechanistic basis of embryonal central nervous system (CNS) tumors, namely medulloblastoma (MB) and pineoblastoma (PB). We study the biological heterogeneity underlying these clinically aggressive embryonal CNS malignancies using a multi-faceted approach spanning genomic studies from patient material, functional validation of novel candidate genes and pathways, and neurobiology studies aimed to define developmental origins. My lab is also developing state-of-the art sequencing and bioinformatics methods to identify tumor signatures via liquid biopsies collected from children enrolled on clinical protocols. This work is leveraged across clinical collaborations to translate biology into tools for diagnosis, risk-stratification, and interpretation of trial outcomes. Our goal is to help devise more effective and less toxic treatment options for affected infants and young children. 

Join the Northcott Research Lab

Selected Publications

See full list of publications

*Denotes shared first authorship
#Denotes shared senior authorship

Tao R*, Han K*, Wu SC*, Friske JD, Roussel MF, Northcott PA. Arrested development: the dysfunctional life history of medulloblastoma. Genes Dev Sep 4, 2024. doi: 10.1101/gad.351936.124. 

Smith KS*, Bihannic L*, Gudenas BL*, Haldipur P, Tao R, Gao Q, Li Y, Aldinger KA, Iskusnykh IY, Chizhikov VV, Scoggins M, Zhang S, Edwards A, Deng M, Glass IA, Overman LM, Millman J, Sjoboen AH, Hadley J, Golser J, Mankad K, Sheppard H, Onar-Thomas A, Gajjar A, Robinson GW, Hovestadt V, Orr BA, Patay Z, Millen KJ,# Northcott PA.# Unified rhombic lip origins of Group 3 and Group 4 medulloblastoma. Nature 609:1012-1020, 2022.

Liu APY, Smith KS, Kumar R, Robinson GW, Northcott PA.# Low-coverage whole-genome sequencing of cerebrospinal-fluid-derived cell-free DNA in brain tumor patients. STAR Protoc 3:101292, 2022. doi:10.1016/j.xpro.2022.101292 PMC9026582

Liu APY, Smith KS, Kumar R, Paul L, Bihannic L, Lin T, Maass KK, Pajtler KW, Chintagumpala M, Su JM, Bouffet E, Fisher MJ, Gururangan S, Cohn R, Hassall T, Hansford JR, Klimo P Jr, Boop FA, Stewart CF, Harreld JH, Merchant TE, Tatevossian RG, Neale G, Lear M, Klco JM, Orr BA, Ellison DW, Gilbertson RJ, Onar-Thomas A, Gajjar A, Robinson GW,# Northcott PA.# Serial assessment of measurable residual disease in medulloblastoma liquid biopsies. Cancer Cell 39:1519-1530 e1514, 2021. doi:10.1016/j.ccell.2021.09.012

Leary SES, Packe RJ, Li Y, Billups CA, Smith KS, Jaju A, Heier L, Burger P, Walsh K, Han Y, Embry L., Hadley J, Kumar R, Michalski J, Hwang E, Gajjar A, Pollack IF, Fouladi M, Northcott PA,# Olson JM.# Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol Sep 1;7(9):1313-1321, 2021. doi:10.1001/jamaoncol.2021.2224

Michalski JM#, Janss AJ, Vezina LG, Smith KS, Billups CA, Burger PC, Embry LM, Cullen PL, Hardy KK, Pomeroy SL, Bass JK, Perkins SM, Merchant TE, Colte PD, Fitzgerald TJ, Booth TN, Cherlow JM, Muraszko KM, Hadley J, Kumar R, Han Y, Tarbell NJ, Fouladi M, Pollack IF, Packer RJ, Li Y, Gajjar A, Northcott PA.# Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol 39:2685-2697, 2021. doi:10.1200/JCO.20.02730

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 39:807-821, 2021. doi:10.1200/JCO.20.01359

Gajjar A, Robinson GW, Smith KS, Lin T, Merchant TE, Chintagumpala M, Mahajan A, Su J, Bouffet E, Bartels U, Schechter T, Hassall T, Robertson T, Nicholls W, Gururangan S, Schroeder K, Sullivan M, Wheeler G, Hansford JR, Kellie SJ, McCowage G, Cohn R, Fisher MJ, Krasin MJ, Stewart CF, Broniscer A, Buchhalter I, Tatevossian RG, Orr BA, Neale G, Klimo P Jr, Boop F, Srinivasan A, Pfister SM, Gilbertson RJ, Onar-Thomas A, Ellison DW,# Northcott PA.# Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03). J Clin Oncol 39:822-835, 2021. doi:10.1200/JCO.20.01372

Smith KS*, Xu K*, Mercer KS, Boop F, Klimo P, DeCupyere M, Grenet J, Robinson S, Dunphy P, Baker SJ, Ellison DW, Merchant TE, Upadayaya SA, Gajjar A, Wu G, Orr BA, Robinson GW#, Northcott PA# & Roussel MF.0# Patient-derived orthotopic xenografts of pediatric brain tumors: a St. Jude resource. Acta Neuropathol, doi:10.1007/s00401-020-02171-5, 2020.

Waszak SM*, Robinson GW*, Gudenas BL, Smith KS, Forget A, Kojic M, Garcia-Lopez J, Hadley J, Hamilton KV, Indersie E, Buchhalter I, Kerssemakers J, Jager N, Sharma T, Rausch T, Kool M, Sturm D, Jones DTW, Vasilyeva A, Tatevossian RG, Neale G, Lombard B, Loew D, Nakitandwe J, Rusch M, Bowers DC, Bendel A, Partap S, Chintagumpala M, Crawford J, Gottardo NG, Smith A, Dufour C, Rutkowski S, Eggen T, Wesenberg F, Kjaerheim K, Feychting M, Lannering, B, Schuz J, Johansen C, Andersen TV, Roosli M, Kuehni CE, Grotzer M, Remke M, Puget S, Pajtler KW, Milde T, Witt O, Ryzhova M, Korshunov A, Orr BA, Ellison DW, Brugieres L, Lichter P, Nichols KE, Gajjar A, Wainwright BJ, Ayrault O, Korbel, JO#, Northcott PA# & Pfister SM# Germline Elongator mutations in Sonic Hedgehog medulloblastoma. Nature 580, 396-401, 2020. doi:10.1038/s41586-020-2164-5.

Liu APY*, Gudenas B*, Lin T, Orr BA, Klimo P Jr, Kumar R, Bouffet E, Gururangan S, Crawford JR, Kellie SJ, Chintagumpala M, Fisher MJ, Bowers DC, Hassall T, Indelicato DJ, Onar-Thomas A, Ellison DW, Boop FA, Merchant TE, Robinson GW, Northcott PA# & Gajjar A.# Risk-adapted therapy and biological heterogeneity in pineoblastoma: integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials. Acta Neuropathol 139, 259-271, 2020. doi:10.1007/s00401-019-02106-9.

Hovestadt V, Ayrault O, Swartling FJ, Robinson GW, Pfister, SM & Northcott PA. Medulloblastomics revisited: biological and clinical insights from thousands of patients. Nat Rev Cancer 20, 42-56, 2020. doi:10.1038/s41568-019-0223-8.

Hovestadt V*, Smith KS*, Bihannic L*, Filbin MG*, Shaw ML, Baumgartner A, DeWitt JC, Groves A, Mayr L, Weisman HR, Richman AR, Shore ME, Goumnerova L, Rosencrance C, Carter RA, Phoenix TN, Hadley JL, Tong Y, Houston J, Ashmun RA, DeCuypere M, Sharma T, Flasch D, Silkov A, Ligon KL, Pomeroy SL, Rivera MN, Rozenblatt-Rosen O, Rusert JM, Wechsler-Reya RJ, Li XN, Peyrl A, Gojo J, Kirchhofer D, Lotsch D, Czech T, Dorfer C, Haberler C, Geyeregger R, Halfmann A, Gawad C, Easton J, Pfister SM, Regev A, Gajjar A, Orr BA, Slavc I, Robinson GW, Bernstein BE#, Suva ML# & Northcott PA.# Resolving medulloblastoma cellular architecture by single-cell genomics. Nature, doi:10.1038/s41586-019-1434-6, 2019.

Northcott PA, Robinson GW, Kratz CP, Mabbott DJ, Pomeroy SL, Clifford SC, Rutkowski S, Ellison DW, Malkin D, Taylor MD, Gajjar A & Pfister SM. Medulloblastoma. Nat Rev Dis Primers 5, 11, 2019. doi:10.1038/s41572-019-0063-6.

Last update: September 2024

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