Trevor Pugh, PhD, FACMG

The Pugh lab is focused on the application of genome sequence analysis as a routine clinical test, particularly as modern cancer treatments are increasingly predicated on genetic information. I am particularly interested in genome analysis of serial biopsies and circulating tumour DNA collected during clinical trials, genetic relationships amongst metastatic sites suggestive of effective combination therapies, and oncogenic mechanisms underlying rare tumours of unknown etiology, particularly pediatric cancers. I also spend part of my time supporting diagnostic testing as a clinical molecular geneticist through the CLIA-certified Advanced Molecular Diagnostics Laboratory at the Princess Margaret Cancer Centre.

Cancers arise due to changes in genetic sequence and structure that alter the biology of normal cells. Large-scale studies have uncovered differing mutation rates across cancer types, with the lowest rates found in pediatric (Pugh et al. Nature. 2012, Pugh et al. Nat Genet. 2013) and hematologic malignancies (Wang et al. N Engl J Med. 2011) and the highest rates in environmentally associated cancers, such as lung cancer (smoking, Imielinski et al. Cell. 2012) and melanoma (sun exposure, Berger et al. Nature. 2012). Recurrent somatic alterations of cancer genomes have been found within and across cancer types, leading to the identification of new biological subtypes and an understanding of mechanisms disrupted in tumours regardless of tissue site. This observation emphasizes a need to transition from an anatomical- to a molecular-based classification of tumours and reveals opportunities for use of targeted therapies across tumour types, if strong genotype/phenotype associations are known.

To begin linking genomic genotypes to clinical phenotypes, our laboratory seeks to enable comprehensive genomic profiling of consistently ascertained and treated cancer specimens. Specifically, we are conducting high-resolution examinations of tumour DNA, RNA and epigenetic marks from primary tumour biopsies; examinations that are now feasible due to continued advancements in DNA sequencing technology. Termed "next-generation sequencing" (NGS), advanced DNA sequencing methods have enabled routine analysis of all genetic content (whole genome sequencing, WGS), all annotated genes (whole exome sequencing, WES), all expressed genes (RNA sequencing, RNA-Seq) and regulators of gene expression (e.g. epigenetic marks, histone binding sites, and DNA/protein interactions) in tissues and, more recently, single cells. These data types are highly complementary and analysis of one large-scale data set greatly informs another. Therefore, we are developing laboratory and computational approaches to extract multiple sources of genome variation from suboptimal tumour specimens, and to integrate these data types into cohesive portraits of individual tumour biology. Part of our work focuses on translation of these findings into clinical practice through nomination of clinically-informative markers for targeted testing and development of bioinformatics tools to support clinical laboratory workflows.
Genome Res. 2019 Aug;29(8):1211-1222
Johnston MJ, Nikolic A, Ninkovic N, Guilhamon P, Cavalli FMG, Seaman S, Zemp FJ, Lee J, Abdelkareem A, Ellestad K, Murison A, Kushida MM, Coutinho FJ, Ma Y, Mungall AJ, Moore R, Marra MA, Taylor MD, Dirks PB, Pugh TJ, Morrissy S, St Croix B, Mahoney DJ...
Nature. 2019 May 01;:
Vladoiu MC, El-Hamamy I, Donovan LK, Farooq H, Holgado BL, Sundaravadanam Y, Ramaswamy V, Hendrikse LD, Kumar S, Mack SC, Lee JJY, Fong V, Juraschka K, Przelicki D, Michealraj A, Skowron P, Luu B, Suzuki H, Morrissy AS, Cavalli FMG, Garzia L, Daniels C...
J Clin Invest. 2019 04 01;129(4):1801
Lee DD, Leão R, Komosa M, Gallo M, Zhang CH, Lipman T, Remke M, Heidari A, Nunes NM, Apolónio JD, Price AJ, De Mello RA, Dias JS, Huntsman D, Hermanns T, Wild PJ, Vanner R, Zadeh G, Karamchandani J, Das S, Taylor MD, Hawkins CE, Wasserman JD,...
Cancer Res. 2019 May 01;79(9):2111-2123
Hoffman M, Gillmor AH, Kunz DJ, Johnston MJ, Nikolic A, Narta K, Zarrei M, King J, Ellestad K, Dang NH, Cavalli FMG, Kushida MM, Coutinho FJ, Zhu Y, Luu B, Ma Y, Mungall AJ, Moore R, Marra MA, Taylor MD, Pugh TJ, Dirks PB, Strother D, Lafay-Cousin L,...
J Clin Invest. 2018 Oct 25;:
Lee DD, Leão R, Komosa M, Gallo M, Zhang CH, Lipman T, Remke M, Heidari A, Nunes NM, Apolónio JD, De Mello RA, Dias J, Huntsman D, Hermanns T, Wild PJ, Vanner R, Zadeh G, Karamchandani J, Das S, Taylor MD, Hawkins CE, Wasserman JD, Figueiredo A,...
Nature. 2017 Aug 30;:
Lan X, Jörg DJ, Cavalli FMG, Richards LM, Nguyen LV, Vanner RJ, Guilhamon P, Lee L, Kushida MM, Pellacani D, Park NI, Coutinho FJ, Whetstone H, Selvadurai HJ, Che C, Luu B, Carles A, Moksa M, Rastegar N, Head R, Dolma S, Prinos P, Cusimano MD, Das S,...
Nat Commun. 2017 Aug 04;8(1):186
Agnihotri S, Suppiah S, Tonge PD, Jalali S, Danesh A, Bruce JP, Mamatjan Y, Klironomos G, Gonen L, Au K, Mansouri S, Karimi S, Sahm F, von Deimling A, Taylor MD, Laperriere NJ, Pugh TJ, Aldape KD, Zadeh G
Nature. 2017 Jul 06;547(7661):55-60
Rheinbay E, Parasuraman P, Grimsby J, Tiao G, Engreitz JM, Kim J, Lawrence MS, Taylor-Weiner A, Rodriguez-Cuevas S, Rosenberg M, Hess J, Stewart C, Maruvka YE, Stojanov P, Cortes ML, Seepo S, Cibulskis C, Tracy A, Pugh TJ, Lee J, Zheng Z, Ellisen LW,...
JCI Insight. 2016 Nov 17;1(19):e87062
Sholl LM, Do K, Shivdasani P, Cerami E, Dubuc AM, Kuo FC, Garcia EP, Jia Y, Davineni P, Abo RP, Pugh TJ, van Hummelen P, Thorner AR, Ducar M, Berger AH, Nishino M, Janeway KA, Church A, Harris M, Ritterhouse LL, Campbell JD, Rojas-Rudilla V, Ligon AH,...
PLoS Genet. 2016 Aug;12(8):e1006242
Giannikou K, Malinowska IA, Pugh TJ, Yan R, Tseng YY, Oh C, Kim J, Tyburczy ME, Chekaluk Y, Liu Y, Alesi N, Finlay GA, Wu CL, Signoretti S, Meyerson M, Getz G, Boehm JS, Henske EP, Kwiatkowski DJ


Assistant Professor, Department of Medical Biophysics, University of Toronto
Lead, Clinical Genomics Program, Princess Margaret Cancer Centre