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About Sickkids
About SickKids

Sean Egan, PhD

Research Institute
Senior Scientist
Cell Biology

University of Toronto
Full Professor
Department of Molecular Genetics


Phone: 416-813-7654 ext. 305267
Fax: 416-813-5252
Email: segan@sickkids.ca
Alternate Phone: 416-813-7654 ext. 206518

Academic Background

  • 1979-1983: University of Manitoba. B.Sc. Honours - Biochemistry
  • 1984-1989: University of Manitoba. PhD, Molecular Biology - Metastasis
  • 1989-1992: Whitehead Institute for Biomedical Research. PDF - Signal Transduction
  • 1992-1993: Imperial Cancer Research Fund, London, UK. Visiting Scientist - Signal Transduction

Research Interests

The Egan lab uses animal models to study development of the mammary gland and lung as well as cancer in both tissues.  For example, we use gene targeting to design models for breast cancer which can be probed to define cooperative signaling networks involved in transformation and metastasis, and that can be targeted in the clinic. 

Analysis of the Fringe/Notch signaling system in mammary development/breast cancer
The Notch family receptors have been implicated in development of most tissues in complex animals. We are interested in how and when Notch receptors are activated in vivo. To this end we previously identified mammalian Fringe proteins (Lunatic, Manic and Radical Fringe), which control Notch activation in response to Delta and Serrate family ligands. We have gone on to study expression and function of Notch pathway genes in mammary gland development and breast cancer.  Indeed, we found that high-level co-expression of JAG1 and NOTCH1 or NOTCH3 is associated with poor prognosis in breast cancer patients, and that JAG1 and NOTCH1 expression are typically found in basal-like breast tumours.  We have also found that deletion of Lfng, a sugar transferase that prevents Notch activation by Jagged ligands, caused enhanced stem/progenitor cell proliferation. Indeed, mammary specific deletion of Lfng induces basal-like tumours with accumulation of Notch intracellular domain fragments and amplification of the Met/Caveolin locus. Interestingly, human BL breast tumours, commonly associated with elevated MET signaling and Caveolin accumulation, express low levels of LFNG.  More recently, we are using this model to determine how Notch and Met interact in BL BC, and how this can be exploited therapeutically.

Defining the cooperative network of mutations involved in epithelial cancer by mouse modeling.
We have begun to develop animal models for cancer that are dependent on tissue-specific expression of PIK3CA or TP53. These models are being crossed with lineage specific dominant or recessive oncogenes to test for specific cooperation and to define how certain signaling pathway combinations dictate tumor subtype.  Indeed, by combining PIK3CA and TP53 mutations in mammary epithelium, we found that these genes cooperate to induce mammary tumours and that the spectrum of tumor subtypes observed in double mutant animals is distinct from that seen in single mutants.  More recently, we are using genome wide approaches to identify oncogenic networks involved in different mammary tumor types, and also to define events involved in metastatic dissemination of tumours.

External Funding

  • The Terry Fox Foundation
  • Canadian Breast Cancer Foundation
  • Canadian Cancer Society Research Institute
  • Cancer Research Society

Publications

For a complete list of publications, please visit PubMed.

Sengar AS, Ellegood J, Yiu AP, Wang H, Wang W, Juneja SC, Lerch JP, Josselyn SA, Henkelman RM, Salter MW*, Egan SE*. (2013) Vertebrate Intersectin1 is repurposed to facilitate cortical midline connectivity and higher order cognition. *Corresponding authors. The Journal of Neuroscience. 33(9):4055-4065. 

Xu K, Usary J, Kousis PC, Prat A, Wang DY, Adams JR, Wang W, Loch AJ, Deng T, Zhao W, Cardiff RD, Yoon K, Gaiano N, Ling V, Beyene J, Zacksenhaus E, Gridley T, Leong WL, Guidos CJ, Perou CM, Egan SE. (2012) Lunatic fringe deficiency cooperates with the Met/Caveolin gene amplicon to induce basal-like breast cancer. Cancer Cell. 21(5):626-41. 

Xu K, Moghal N, Egan SE. (2012) Notch signaling in lung development and disease. Advances in Experimental Medicine and Biology. 727:89-98.

Adams JR, Xu K, Liu JC, Agamez NM, Loch AJ, Wong RG, Wang W, Wright KL, Lane TF, Zacksenhaus E, Egan SE. (2011) Cooperation between Pik3ca and p53 mutations in mouse mammary tumor formation. Cancer Research. 71(7):2706-2717.

Xu K, Nieuwenhuis E, Cohen BL, Wang W, Canty AJ, Danska JS, Coultas L, Rossant J, Wu MY, Piscione TD, Nagy A, Gossler A, Hicks GG, Hui CC, Henkelman RM, Yu LX, Sled JG, Gridley T, Egan SE. (2010) Lunatic Fringe-mediated Notch signaling is required for lung alveogenesis. American Journal of Physiology - Lung and Molecular Physiology. 298(1):L45-56.

Tan JB, Xu K, Cretegny K, Visan I, Yuan JS, Egan SE, Guidos CJ. (2009) Lunatic and manic fringe cooperatively enhance marginal zone B cell precursor competition for delta-like 1 in splenic endothelial niches. Immunity. 30(2):254-63.

Reedijk M, Odorcic S, Zhang H, Chetty R, Tennert C, Dickson BC, Lockwood G, Gallinger S, Egan SE. (2008) Activation of Notch signaling in human colon adenocarcinoma. International Journal of Oncology 33(6):1223-1229.

Wang W, Bouhours M, Gracheva EO, Liao EH, Xu K, Sengar AS, Xin X, Roder J, Boone C, Richmond JE, Zhen M, Egan SE. (2008) ITSN-1 controls vesicle recycling at the neuromuscular junction and functions in parallel with DAB-1. Traffic. 9(5):742-754.

Reedijk M, Pinnaduwage D, Dickson BC, Mulligan A-M, Zhang H, Bull SB, O’Malley FP, Egan SE*, Andrulis IL*. (2008) JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer. *Corresponding authors. Breast Cancer Research and Treatment. 111(3):439-448.

Egan SE, Sengar AS. (2006) Intersectin2 AfCS-Nature Molecule Pages (doi:10.1038/mp.a000881.01).

Reedijk M, Odorcic S, Chang L, Zhang H, Miller N, McCready D, Lockwood G, Egan SE. (2005) High-level co-expression of JAG1 and NOTCH1 is observed in human breast cancer and is associated with poor overall survival. Cancer Research. 65(18):8530-8537.