I am currently a postdoctoral research associate with Obi Griffith and Elaine Mardis at the McDonnell Genome Institute of Washington University in St. Louis, where we are investigating the genomic architecture of cancer.
In one project, we are studying features associated with response to trastuzumab in HER2-positive breast cancer. This includes the identification of recurrent somatic mutations, gene fusions, copy number alterations, as well as other genomic and transcriptomic changes. Our study aims 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 series of other projects, we have been identifying highly validated regulatory sites within the human genome. In part, we are planning to use this information to update the ORegAnno database. Moreover, we are using this information in conjunction with targeted sequencing of TCGA breast cancer samples to analyze recurrent alterations in the regulatory regions of the disease.
My Ph.D. research was in Mike Hallett's group at McGill University, and focused on developing and applying bioinformatics tools to breast cancer. This included the production of a novel framework, termed Breast Signature Analysis Tool (BreSAT), for quantifying associations between signature activation levels and clinicopathological features such as patient outcome. Another project 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 Sorlie, we have 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.
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 *Authors contributed equally to the work
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 *Authors contributed equally to the work
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
|Genomic characterisation of HER2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy - results from the ACOSOG Z1041 (Alliance) trial.||Ann Oncol. 2017 Feb 21. doi: 10.1093/annonc/mdx048.||2017-02-21|
|CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer||Nat Genet. 2017 Jan 31;49(2):170-174. doi: 10.1038/ng.3774.||2017-01-31|
|CIViC: A knowledgebase for expert-crowdsourcing the clinical interpretation of variants in cancer||doi: http://dx.doi.org/10.1101/072892|
|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. doi: 10.1016/j.exphem.2016.04.011. Epub 2016 May 13||2016-07-01|
|ORegAnno 3.0: a community-driven resource for curated regulatory annotation.||Nucleic Acids Res. 2015 Nov 17. pii: gkv1203. [Epub ahead of print]||2015-11-17|