: BIOGRAPHICAL SKETCH

Program Director/Principal Investigator (Last, First, Middle) : Murphy, Leigh C.
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2.
Follow this format for each person. DO NOT EXCEED FOUR PAGES.
NAME
POSITION TITLE
Leigh C. Murphy
Professor, Dept of Biochemisty & Medical Genetics,
University of Manitoba
Senior Scientist, Manitoba Institute of Cell Biology
University of Manitoba and CancerCare Manitoba
eRA COMMONS USER NAME (credential, e.g., agency login)
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
DEGREE
(if applicable)
YEAR(s)
BSc (Hons)
1973
Biochemistry
PhD
1976
Endocrinology
INSTITUTION AND LOCATION
University of Sydney, Australia
University of Sydney, Austria
A.
FIELD OF STUDY
Personal Statement
I have been working on various aspects of breast cancer research since my first postdoctoral position, in 1977.
My research since establishing my independent research program has focused and continues to focus
primarily on estrogen receptors (ERs). Estrogen affects breast cells by binding to ERs, which are proteins in
breast cancer cells. It was long believed that there was only one kind of estrogen receptor, but another ER has
been found, and so has several types of alternatively spliced variant of each type of ER. My lab was one of the
first to establish the expression of alternatively spliced variant forms of ERalpha in human breast tumors. My
lab was the first to show that the second ER, ERbeta was expressed in some human breast tumors. We
established that there are two types of breast tumors expressing ER-beta: those that express both ER-alpha
(the original ER) and ER-beta and those that express ER-beta alone. Our results suggest that the function of
ERbeta when expressed with ERalpha is different to when it is expressed alone. Those tumors with ERalpha
and high levels of ERbeta respond differently to Tamoxifen, the most commonly prescribed anti-estrogen drug
therapy, when compared to tumors that expressed ERalpha with low levels of ERbeta. Our published results
suggest that in ER positive tumors, ERbeta levels help to predict whether Tamoxifen and/or endocrine therapy
will be effective in breast cancer patients. However, our data suggest that tumors which express high levels of
ERbeta alone in the absence of ERalpha are likely to be more aggressive tumors. In addition my lab was the
first to detect phosphorylated forms of ERalpha in multiple human breast tumors and identify a novel
phosphorylation code for ERalpha which has the potential to be a more precise biomarker of treatment
response in breast cancer than currently available. It is possible that in the near future these studies will lead to
the development of a clinical test allowing physicians to test more precisely patients’ responsiveness to
endocrine therapy prior to prescribing treatment. More recently my lab has shown that ERalpha is a novel
substrate of mTOR and identified the location of phosphorylated forms of ERalpha at the centrosomes and
midbody during mitosis and cytokinesis, suggesting novel functions of the phosphorylated receptor directly in
mitosis.
B.
Positions and Honors
Professional Experience
Dates
University, Company or Organization
1977-78
Dept of Medicine, University of Sydney, Australia
1979-84
Ludwig Institute for Cancer research (Sydney Branch)
1985-87
Dept of Physiology, University of Manitoba
1987-91
Dept of Biochemistry, University of Manitoba
1991-95
Dept of Biochemistry & Mol Biology, University of Manitoba
1995-99
Dept of Biochemistry & Mol Biology, University of Manitoba
1999-present
Dept of Biochemistry & Med Genetics, University of Manitoba
0925-0001/0002 (Rev. 08/12)
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Rank or Title
Postdoctoral Fellow
Research Fellow
Postdoctoral Fellow
Assistant Professor
Assistant Professor
Professor (tenured)
Professor (tenured)
Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle) : Murphy, Leigh C.
2000-present
2006-08
2007-present
2009-11
Manitoba Institute of Cell Biology, CancerCareMB & U of Manitoba
Manitoba Institute of Cell Biology
Manitoba Tumour Bank
Manitoba Institute of Cell Biology
Senior Scientist
Associate Director
Co-Director
Acting Director
Selected Other Experience and Professional Memberships
Dates
University, Company or Organization
1990, 1994
Site review team, National Cancer Institute
1991-96, 1999-03
National Cancer Institute of Canada/CBCRI, grant review panels
1995-04, 08, 10, 11 US Army Breast Cancer Program, various grant review panels
2005, 07, 08, 10, 11 Canadian Institutes of Health Research, grant review panel, reviewer, site visit chair
2009-11
Susan Komen various grant review panels
2011-present
Canadian Tumor Repository Network (CTRNet), Management committee member
Honors
Dates
1988-94
1992-93
1994-99
2005
Honors & Awards (selected)
NCIC Scientist career Award
Co-chair CCS and NCIC Joint Task Force on Women and cancer
Medical Research Council of Canada, Scientist Career Award
YMCA-YWCA (Winnipeg) Women of Distinction Award, Research, Science,
Technology, Environment Section
C.
Selected Peer-reviewed Publications
(selected from 147 career pubs, 3 submitted) (trainees underlined)
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8.
Leigh Murphy, Tracy Cherlet, Adewale Adeyinka, Yulian Niu, Linda Snell, Peter Watson. (2004)
Phospho Serine-118 Estrogen Receptor-alpha Detection in Human Breast Tumors in vivo. Clin Cancer
Res: 10, 1354-1359.
Leigh Murphy, Yulian Niu, Linda Snell, Peter Watson.(2004) Phospho-Serine-118 Estrogen Receptoralpha Expression in Primary Human Breast Tumors in vivo is Associated with Better Disease Outcome in
Women Treated with Tamoxifen. Clin Cancer Res 10(17):5902-6.
Charlton Cooper, Guangyu Liu, Yulian Niu, Sylvia Santos, Leigh Murphy and Peter Watson. (2004)
Intermittent Hypoxia Induces Proteasome Dependent Down-regulation of Estrogen Receptor alpha in
Human Breast Carcinoma. Clin Cancer Res, 10:8720-8727.
Gregory E. Weitsman, Lin Li, George Skliris, James R. Davie, Kanyarat Ung, Yulian Niu, Linda CurtisSnell, Ladislav Tomes, Peter H. Watson, Leigh C. Murphy. (2006) Estrogen receptor-alpha
phosphorylated at Serine 118 is present at the promoters of estrogen-regulated genes and is not altered
due to Her2 over-expression. Cancer Res; 66:10162-70.
Gregory E. Weitsman, Wineeta Weebadda, Kanyarat Ung and Leigh C. Murphy (2009) Reactive oxygen
species induce phosphorylation of serine 118 and 167 on estrogen receptor alpha. Breast Cancer
Research & Treatment 118: 269 [2008 Oct 21. Epub ahead of print]
George P. Skliris, Brian G. Rowan , Mariam Al-Dhaheri, Christopher Williams, Sandy Troup , Sanela
Begic, Michelle Parisien, Peter H. Watson, Leigh C. Murphy. (2009) Immunohistochemical validation of
multiple phospho-specific epitopes for estrogen receptor a (ERa) in tissue microarrays (TMA) of
cinomas. Breast Cancer Research and Treatment 118: 443-453.
Yi Yan, George P. Skliris, Carla C. Penner, Shilpa Chooniedass-Kothari S, Charlton Cooper, Zoann
Nugent, Andrea Fristensky, Mohamad K. Hamedani, Anne Blanchard, Yvonne Myal, Leigh C. Murphy,
Etienne Leygue (2009) Steroid Receptor RNA Activator Protein (SRAP): a Potential New Prognostic
Marker for Estrogen Receptor-positive / Node-Negative / Younger Breast Cancer Patients. Breast Cancer
Res 11(5):R67.
Georgios Skliris, Zoann Nugent, Brian Rowan, Carla Penner, Peter Watson, Leigh Murphy. (2010) A
phosphorylation code for estrogen receptor alpha predicts clinical outcome to endocrine therapy in breast
cancer. Endocrine-Related Cancer 17(3):589-97.
PHS 398/2590 (Rev. 05/01)
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Biographical Sketch Format Page
Program Director/Principal Investigator (Last, First, Middle) : Murphy, Leigh C.
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Dominik Domanski, Leigh C. Murphy, Christoph H. Borchers (2010) Assay Development for the
Determination of Phosphorylation Stoichiometry using MRM methods with and without Phosphatase
Treatment: Application to Breast Cancer Signaling Pathways. Analytical Chemistry 82(13):5610-20.
Georgios Skliris, Zoann Nugent, Peter Watson, Leigh Murphy (2010) Estrogen receptor alpha
phosphorylated at tyrosine 537 is associated with poor clinical outcome in breast cancer patients treated
with tamoxifen. Hormones and Cancer 1 (4), pp. 215-221.
Mariam Al-Dhaheri, George Skliris, Jiacai Wu, Jun Li, Ken Higashimato, Yidan Wang, Kevin White,
Yuerong Zhu, Leigh Murphy, Wei Xu. (2011) Identification of CARM1 as an important determinant of
ERα-dependent breast cancer cell differentiation and proliferation. Cancer Res 71(6):2118-28.
Nathan R. West, Leigh C. Murphy, and Peter H. Watson (2012) Oncostatin-M suppresses estrogen
receptor-a expression and is associated with poor outcome in human breast cancer. Endocrine Related
Cancer 19(2):181-95.
Christina Curtis, Sohrab P. Shah, Suet-Feung Chin, Gulisa Turashvili, Oscar M.Rueda, Mark J. Dunning,
Doug Speed, Andy G. Lynch Shamith Samarajiwa, YinyinYuan, Stefan Gr¨af, Gavin Ha, Gholamreza H,
Ali Bashashati, Roslin Russell, StevenMcKinney, METABRIC Group, Anita Langerød, Andrew Green,
Elena Provenzano, Gordon Wishart, Sarah Pinder, Peter Watson, Florian Markowetz, Leigh Murphy, Ian
Ellis, Arnie Purushotham, Anne-Lise Børresen-Dale, James D. Brenton, Simon Tavar´e, Carlos Caldas &
Samuel Aparicio. (2012) The integrative genomic and transcriptomic architecture of 1000 breast tumours
reveals novel subgroups. Nature 486(7403):346-52.
E.A. Matzke, S. O’Donoghue, R.O. Barnes, H. Daudt, S. Cheah, A. Suggitt, J. Bartlett, S. Damaraju, R.
Johnston, L. Murphy, L. Shepherd, A.M. Mes-Masson, B. Schacter, P. Watson. (2012) Certification for
Biobanks: The Program Developed by the Canadian Tumour Repository Network (CTRNet).
Biopreservation and Biobanking 10/5:426-432.
Yi Yan, Anne Blanchard, Xiao Li, Vivien H.C. Bramwell, Kathleen I. Pritchard, Dongsheng Tu, Lois
Shepherd, Yvonne Myal, Carla Penner, Peter Watson, Etienne Leygue, Leigh Murphy (2013)
Expression of both Estrogen Receptor-beta 1 (ER-b1) and its co-regulator Steroid Receptor RNA
Activator Protein (SRAP) are Predictive for Benefit From Tamoxifen Therapy in Patients with Estrogen
Receptor-alpha (ER-a) Negative Early Breast Cancer (EBC). Annals Oncology 24(8):1986-93.
Peter H. Watson, Sara Y. Nussbeck, Candace Carter, Sheila O’Donoghue, Stefanie Cheah, Rebecca
Barnes, John Bartlett, Jane Carpenter, William Grizzle, Randy Johnston, Anne-Marie Mes-Masson,
Leigh Murphy, Katherine Sexton, Lois Shepherd, Daniel Simeon-Dubach, Nik Zeps, Brent Schacter.
(2014) A Framework for Biobank Sustainability. Biopreservation and Biobanking (in press).
Anuraag Shrivastav, M Chrissie Bruce, Danira Jaksic, Tarek Bader, Sri Seekallu, Carla Penner, Zoann
Nugent, Peter Watson, Leigh Murphy. The Mammalian Target for Rapamycin Pathway is Associated
with the Phosphorylation Score (P7) for Estrogen Receptor-a in Human Breast Tumors, in vivo. (2014)
Breast Cancer Res 16(3):R49.
Invited reviews. (Selected from 52 career)
1.
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L.C.Murphy, G.P.Skliris, B. Rowan*, M. Al-Dhaheri*, C Williams*, C. Penner, S. Troup, S. Begic,
Michelle Parisien, P.H.Watson (2009) The Relevance of Phosphorylated Forms of Estrogen Receptor in
Human Breast Cancer in vivo . J Steroid Biochem Mol Biology 114: 90-95
Leigh C Murphy, Srivinas Seekallu, Peter H Watson. (2011) Clinical Significance of Estrogen Receptor
Phosphorylation. Endocrine-Related Cancer,18(1):R1-R14. (peer reviewed invited review)
Anuraag Shrivastav, Leigh Murphy. (2012) Involvement of PI-3K/Akt/mTOR signaling in the activation
of estrogen receptor in breast cancer. Breast Cancer Management. 1 (3); 235-249 (peer reviewed
invited review).
Murali Anbalagan, Brandy Huderson, Leigh Murphy, Brian G. Rowan. (2012) Post-translational
modifications of nuclear receptors and human disease. Nuclear Receptor Signaling 10:e001 (invited
review)
Jill I. Murray, Nathan R. West, Leigh C. Murphy, Peter H. Watson. (2014) Intratumoral inflammation
and endocrine resistance in breast cancer. Endocrine Related Cancer. (invited review, in press)
PHS 398/2590 (Rev. 09/04)
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Continuation Format Page
Program Director/Principal Investigator (Last, First, Middle) : Murphy, Leigh C.
6.
M Chrissie Bruce, Danielle McAllister, Leigh C Murphy. (2014) The Kinome Associated with Estrogen
Receptor Positive Status in Human Breast Cancer. Invited review Endocrine Related Cancer
21(5):R357-70.
Leigh Murphy: H index = 51
Results from 180 items
Sum of the Times Cited = 7646
Average Citations per Item = 42.48
D.
Research Support
Grants Currently Held since Jan 2014
1. Beyond the Estrogen Receptor: involvement of mechanistic target of rapamycin (mTOR) in estrogen
signaling in normal and malignant human breast epithelial cells.
CBCF-Prairies/NWT $125,000/yr 2014-2017
(P.I. LCM; coApp Peter Watson and Afshin Raouf) 0% overlap
2. Determination of the Phosphorylated Estrogen Receptor Alpha Cistrome in human breast tumour in
vivo.
CBCF-Prairies/NWT $120,000/yr 2012-2014
(P.I. LCM)
3. Epigenetic-like codes for estrogen receptor alpha (ERa): ERa phosphorylation profiling ex vivo in
human breast tumours.
CCSRI-Innovation grant $100,000/yr 2012-2014
(P.I.) (coPI, C Borchers, D Domanski, P Watson)
4. Beyond the Estrogen Receptor: involvement of kinases in estrogen dependence and independence
in human breast cancer.
CIHR-operating- MOP-14742 $120,143/yr 1/10/2004 to 30/09/2014
(P.I. LCM); (coPI, P Watson) 0% overlap
Grants previously held over last 5 years
1. Hormone Use, Estrogen Receptor Expression and Survival of Women with Non-Small Cell Lung
Cancer: A Manitoba Perspective
MMSF $25,000/yr 2010-2011
(CoPI) (P.I. G Harding) 0% overlap
2. A Differential Role of ERbeta in Early versus Metastatic Non-small Cell Lung Cancer.
CCMF $60,000/yr 1/07/2010-30/06/2011
(P.I.) 0% overlap
3. The Role of the Long and Short Isoforms of Estrogen Receptors Beta in Inflammation in Breast
Cancer
CBCF/Prairies/NWT Chapter $100,000/yr 1/04/2009 to 31/03/2011
(P.I.) 0% overlap
4. The Role of the Long and Short Isoforms of Estrogen Receptors Beta in Prostate Cancer
PCRFC $60,000/yr 1/07/2009- 30/06/2010
(P.I.) 0% overlap
5. The Manitoba Breast Tumor Bank.
CIHR-Research Resource Grant PRG 80155 $105,065/yr 1/06/2006 to 31/05/2011
(CoPI) (P.I. Peter Watson) 0% overlap
PHS 398/2590 (Rev. 09/04)
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