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.

For a list of Dr. Pugh's publications, please visit PubMed, Scopus, Europe PMC or ORCID.

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