Research

Current Work

I'm a Senior Bioinformatician, Data Scientist with the Mital lab at The Hospital for Sick Children (SickKids).

I'm investigating the genomics of childhood heart disease. Our goals are to identify gene defects that cause heart disease in children, to understand how these variants influence disease severity and outcome, to apply this knowledge to inform the clinical care of children with heart disease, and to discover new therapies for pediatric heart failure.

Previous Work

I previously worked as a Bioinformatician, Data Scientist with the Boutros lab at the Ontario Institute for Cancer Research (OICR). There I developed a machine learning pipeline to identify the optimal sets of data types and parameters for diagnostic and prognostic biomarkers in prostate cancer. I also led development of our group's in-house, Perl-based genomics analysis pipeline, which ties together software tools into a unified framework for automated processing and QC of sequencing data.

As a Postdoctoral Research Associate with Obi Griffith and Elaine Mardis at the McDonnell Genome Institute of Washington University in St. Louis, I investigated the genomics of response to neoadjuvant trastuzumab and chemotherapy in HER2-positive breast cancer, including the identification of recurrent somatic mutations, gene fusions, copy number alterations, neoantigens, and transcriptional changes. Our study aimed to identify alternative, druggable targets for those patients that do not respond to the current standard of care in HER2-positive breast cancer. In a separate study, I identified highly curated regulatory sites within the human genome and then worked with NimbleGen/Roche to design a capture reagent targeting the human regulome. We then performed targeted sequencing of these regions in breast cancer cases in order to identify recurrent regulatory mutations in the disease, and sought to associate these mutations with gene expression changes and prognostic outcome.

My Ph.D. research was in Mike Hallett's group at McGill University, and focused on applying bioinformatics tools to breast cancer. This included the development of a de novo framework, termed Absolute Inference of Patient Signatures (AIPS), for analyzing molecular signatures in breast cancer. As a part of this project, we collected and annotated thousands of signatures and breast cancer samples, and further developed statistical tests to determine associations between signatures and clinicopathological features such as patient outcome. Another set of projects involved investigating the role of the oncogene MET in mouse models of breast cancer. This was in collaboration with Marisa Ponzo and Jennifer Knight from Morag Park's group. We determined that MET is associated with triple-negative breast cancer, and that expression of MET synergizes with loss of p53 to induce a claudin-low phenotype. Finally, in collaboration with Therese Sørlie, we investigated molecular features of progression from non-invasive to invasive breast cancer. We observed that many of the strongest discriminators of tumor invasiveness are subtype-specific, indicating that vastly different mechanisms may lead to disease progression in breast cancer.

Publications

Click here to search for up-to-date publications on PubMed.

Bhandari V, Hoey C, Liu LY, Lalonde E, Ray J, Livingstone J, Lesurf R, Shiah YJ, Vujcic T, Huang X, Espiritu SMG, Heisler LE, Yousif F, Huang V, Yamaguchi TN, Yao CQ, Sabelnykova VY, Fraser M, Chua MLK, van der Kwast T, Liu SK, Boutros PC, Bristow RG. Molecular landmarks of tumor hypoxia across cancer types. Nature Genetics. 2019 Feb;51(2):308-318. PMID: 30643250

Lesurf R, Griffith OL, Griffith M, Hundal J, Trani L, Watson MA, Aft R, Ellis MJ, Ota D, Suman VJ, Meric-Bernstam F, Leitch AM, Boughey JC, Unzeitig G, Buzdar AU, Hunt KK, Mardis ER. Genomic characterisation of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy - results from the ACOSOG Z1041 (Alliance) trial. Annals of Oncology. 2017 May 1;28(5):1070-1077. PMID: 28453704

Whyte MP, Griffith M, Trani L, Mumm S, Gottesman GS, McAlister WH, Krysiak K, Lesurf R, Skidmore ZL, Campbell KM, Rosman IS, Bayliss S, Bijanki VN, Nenninger A, Van Tine BA, Griffith OL, Mardis ER. Melorheostosis: Exome sequencing of an associated dermatosis implicates postzygotic mosaicism of mutated KRAS. Bone. 2017 Aug;101:145-155. PMID: 28434888

Paquet ER*, Lesurf R*, Tofigh A, Dumeaux V, Hallett MT. Detecting gene signature activation in breast cancer in an absolute, single-patient manner. Breast Cancer Research. 2017 Mar 21;19(1):32. PMID: 28327201

Griffith M, Spies NC, Krysiak K, McMichael JF, Coffman AC, Danos AM, Ainscough BJ, Ramirez CA, Rieke DT, Kujan L, Barnell EK, Wagner AH, Skidmore ZL, Wollam A, Liu CJ, Jones MR, Bilski RL, Lesurf R, Feng Y, Shah NM, Bonakdar M, Trani L, Matlock M, Ramu A, Campbell KM, Spies GC, Graubert AP, Gangavarapu K, Eldred JM, Larson DE, Walker JR, Good BM, Wu C, Su AI, Dienstmann R, Margolin AA, Tamborero D, Lopez-Bigas N, Jones SJM, Bose R, Spencer DH, Wartman LD, Wilson RK, Mardis ER, Griffith OL. CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer. Nature Genetics. 2017 Jan 31;49(2):170-174. PMID: 28138153

Lesurf R, Aure MR, Mørk HH, Vitelli V, OSBREAC, Lundgren S, Børresen-Dale AL, Kristensen V, Wärnberg F, Hallett M, Sørlie T. Molecular features of subtype-specific progression from ductal carcinoma in situ to invasive breast cancer. Cell Rep. 2016 Jul 26;16(4):1166-79. PMID: 27396337

Skidmore ZL, Wagner AH, Lesurf R, Campbell KM, Kunisaki J, Griffith OL, Griffith M. GenVisR: Genomic Visualizations in R. Bioinformatics. 2016 Jun 10. pii: btw325. PMID: 27288499

Griffith M, Griffith OL, Krysiak K, Skidmore ZL, Christopher MJ, Klco JM, Ramu A, Lamprecht TL, Wagner AH, Campbell KM, Lesurf R, Hundal J, Zhang J, Spies NC, Ainscough BJ, Larson DE, Heath SE, Fronick C, O'Laughlin S, Fulton R, Magrini V, McGrath S, Smith SM, Miller CA, Maher CA, Payton JE, Walker JR, Eldred JM, Walter MJ, Link DC, Graubert TA, Westervelt P, Kulkarni S, DiPersio JF, Mardis ER, Wilson RK, Ley TJ. Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B lymphoblastic leukemia. Exp Hematol. 2016 Jul;44(7):603-13. PMID: 27181063

Lesurf R, Cotto KC, Wang G, Griffith M, Kasaian K, Jones SJ, Montgomery SB, Griffith OL; Open Regulatory Annotation Consortium. ORegAnno 3.0: a community-driven resource for curated regulatory annotation. Nucleic Acids Res. 2016 Jan 4;44(D1):D126-32. PMID: 26578589

Tofigh A, Suderman M, Paquet ER, Livingstone J, Bertos N, Saleh SM, Zhao H, Souleimanova M, Cory S, Lesurf R, Shahalizadeh S, Garcia Lopez N, Riazalhosseini Y, Omeroglu A, Ursini-Siegel J, Park M, Dumeaux V, Hallett M. The prognostic ease and difficulty of invasive breast carcinoma. Cell Rep. 2014 Oct 9;9(1):129-42. PMID: 25284793

Vadnais C, Shooshtarizadeh P, Rajadurai CV, Lesurf R, Hulea L, Davoudi S, Cadieux C, Hallett M, Park M, Nepveu A. Autocrine Activation of the Wnt/β-Catenin Pathway by CUX1 and GLIS1 in Breast Cancers. Biol Open. 2014 Sep 12;3(10):937-46. PMID: 25217618

Wallace JA, Li F, Balakrishnan S, Cantemir-Stone CZ, Pecot T, Martin C, Kladney RD, Sharma SM, Trimboli AJ, Fernandez SA, Yu L, Rosol TJ, Stromberg PC, Lesurf R, Hallett M, Park M, Leone G, Ostrowski MC. Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer. PLoS One. 2013 Aug 16;8(8):e71533. PMID: 23977064

Schade B, Lesurf R, Sanguin-Gendreau V, Bui T, Deblois G, O’Toole SA, Millar EKA, Zardawi SJ, Lopez-Knowles E, Sutherland RL, Giguere V, Kahn M, Hallett M, Muller WJ. β-catenin signaling is a critical event in ErbB2-mediated mammary tumor progression. Cancer Res. 2013 Jul 15;73(14):4474-87. PMID: 23720052

Knight JF*, Lesurf R*, Zhao H, Pinnaduwage D, Davis RR, Saleh SM, Zuo D, Naujokas MA, Chughtai N, Herschkowitz JI, Prat A, Mulligan AM, Muller WJ, Cardiff RD, Gregg JP, Andrulis IL, Hallett MT, Park M. Met synergizes with p53 loss to induce mammary tumors that possess features of claudin-low breast cancer. PNAS. 2013 Apr 2;110(14):E1301-10. PMID: 23509284

Ponzo MG*, Lesurf R*, Petkiewicz S, O'Malley FP, Pinnaduwage D, Andrulis IL, Bull SB, Chughtai N, Zuo D, Souleimanova M, Germain D, Omeroglu A, Cardiff RD, Hallett M, Park M. Met induces mammary tumors with diverse histologies and is associated with poor outcome and human basal breast cancer. PNAS. 2009 Aug 4;106(31):12903-8. PMID: 19617568

Schade B, Rao T, Dourdin N, Lesurf R, Hallett M, Cardiff RD, Muller WJ. PTEN deficiency in a luminal ErbB-2 mouse model results in dramatic acceleration of mammary tumorigenesis and metastasis. J Biol Chem. 2009 Jul 10;284(28):19018-26. PMID: 19435886

Dourdin N, Schade B, Lesurf R, Hallett M, Munn RJ, Cardiff RD, Muller WJ. Phosphatase and tensin homologue deleted on chromosome 10 deficiency accelerates tumor induction in a mouse model of ErbB-2 mammary tumorigenesis. Cancer Res. 2008 Apr 1;68(7):2122-31. PMID: 18381417

*Authors contributed equally to the work.

CV

Download the PDF version of my resume here

Bio

Born in Toronto, Ontario, I spent the latter years of my childhood growing up in Peterborough, Ontario. During this time, I had the opportunity to explore much of my home region, including working for 2 months in Wawa, Ontario, on an electrofishing research project led by Leon Carl. Yes, electrofishing is exactly what it sounds like!

In 2002 I pursued a bachelor's degree in Biomedical Computing at Queen's University in Kingston, Ontario. I spent summers working in a variety of different fields, including West Nile virus prevention, autism research, at a microarray facility, and doing prostate cancer research.

Afterwards I continued graduate studies with Mike Hallett's group at McGill University in Montreal, Quebec. There I had the opportunity to work on many important issues related to breast cancer, form collaborations with great researchers, and live in exciting places including Heidelberg and Oslo!

From 2014-2016 I worked as a Postdoctoral Research Associate at the McDonnell Genome Institute of Washington University School of Medicine, where I focused on cancer genomics.

In my spare time, I enjoy a variety of sports and activities, including hockey, softball, hiking, canoeing, camping, and board games with friends. I presently serve as the Play Director and as a Board member with the Toronto Gay Hockey Association (TGHA), where I'm responsible for scheduling ice time and officiating, disseminating the rules of play, evaluating player skill levels, and compiling player statistics.

Contact

                 

Email

Phone

Mailing Address

The Hospital for Sick Children
Peter Gilgan Centre for Research & Learning
16th Floor – 16.9400
686 Bay Street
Toronto, Ontario, Canada
M5G 0A4