• Dunn, Sandra E.

    Titles
    Scientist Level 2, CFRI
    Associate Professor, Division of Hematology and Oncology, Department of Pediatrics, University of British Columbia
    Degrees / Designations
    PhD
    Primary Area of Research
    Childhood Cancer & Blood Research
    Secondary Area(s) of Research
    Phone
    604-875-2000 ext. 6015
    Fax
    604-875-3120
    Lab Phone
    604-875-2000 ext. 6041
    Assistant
    Brenda Tse
    Assistant Phone
    604-875-2000 ext. 4904
    Mailing Address
    Child & Family Research Institute
    Room 3082, 950 West 28th Avenue
    Vancouver, BC V5Z 4H4
    Affiliate Websites
    Research Areas
  • Pediatric oncology
  • Breast cancer research
  • Cancer therapy
  • Chromatin immunoprecipitation
  • Tumour tissue microarray
  • Signal transduction
  • Gene expression arrays
  • Functional proteomics and bioinformatics
Summary

Dr. Sandra Dunn is an Associate Professor in the Department of Pediatrics with joint appointments in the Departments of Experimental Medicine and Medical Genetics at the University of British Columbia. Her laboratory is located at the Child & Family Research Institute where she coordinates the High Content Screening Program. Dr. Dunn is also the CEO and Founder of Phoenix Molecular Diagnostics, a spin-off company established in 2012. Over the past decade, she has had two successful projects with the Centre for Drug Research and Development which have laid the foundation for the therapeutic drug development in oncology.

Since joining UBC in 2001, Dr. Dunn has focused her research on identifying molecular targets to treat cancers affecting children and women such as brain and breast tumors. Despite conventional beliefs, not all cancers are the same. In fact, every cancer is unique, and so broad-based treatments such as chemotherapy are not always effective and often cause much suffering in cancer patients.

Current Projects

Because of this unique nature of cancer cells, Dr. Dunn’s lab has several projects that are ongoing to study the molecular mechanisms and signaling pathways that govern the growth of brain and breast cancer cells. Her ultimate goal is to develop effective molecular diagnostic tests and personalized therapies for patients.

  1. Identify proteins that correlate with cancer metastasis and patient prognosis. Dr. Dunn’s research team has made the exciting discovery that the Polo-Like Kinase 1 (PLK-1) protein is over-expressed in medulloblastoma and glioblastoma brain tumors. When they block this protein with a drug inhibitor, it killed and blocked the growth of a high percentage of the cancer cells while leaving the normal cells unharmed. They are currently studying how they can apply this to the clinic for treating patients with brain tumors.
  2. Ribosomal protein S6 kinase (RSK2) and its downstream protein Y-box binding protein-1 (YB-1) have been shown by the Dunn lab to be essential for the growth of breast cancer. They have begun to identify novel ways of inhibiting RSK2 and YB-1 using small interfering RNAs, antisense, cell permeable peptides, or small molecules.
  3. Because YB-1 is a transcription factor, they are interested in understanding how YB-1 promotes tumor growth using chromatin immunoprecipitation (ChIP) leading to the discovery that it directly regulates EGFR, Her-2 and the Met receptor. Global YB-1 gene targets are being elucidated using ChIP coupled to promoter arrays also known as ChIP-on-Chip. These studies have led to a curious link between YB-1 and cancer stem cells. This is of particular interest because YB-1 is highly associated with cancer recurrence suggesting that it could impart stem cell properties.
  4. Her team is also searching for other potential therapeutic targets for treating cancers using the ArrayScan VIT (Cellomics) high content screen instrument. Once potential molecular targets have been identified using the screen, the molecules of interest will be validated using in vitro and in vivo models that address tumor growth, invasion, and metastasis. They are also developing molecular diagnostic tests for high risk patients using a new cutting edge technology called Nanostring to look at certain genes in patient samples and correlate this with patients’ response to drug treatment and relapse.
  5. Many patients relapsed because they become resistant to the chemotherapeutic drugs. Therefore, the lab is also investigating the underlying causes of drug resistance in order to develop effective strategies to eliminate them to prevent tumor formation and relapse.

Dr. Dunn has trained over 50 students and published more than 73 papers. She holds two patents for novel anticancer agents and is the founder of Phoenix Molecular Diagnostics, a newly established spin-off company. Her research is supported by the B.C. Children's Hospital Foundation, the Michael Cuccione Foundation, Canadian Institute for Health Research, Canadian Breast Cancer Foundation, MITACS, Hannah's Heroes Foundation, and Summits of Hope.

Selected Publications

Triscott J, Lee C, Foster C, Manoranjan B, Pambid MR, Berns R, Fotovati A, Venugopal C, O'Halloran K, Narendran A, Hawkins C, Ramaswamy V, Bouffet E, Taylor MD, Singhal A, Maxwell CA, Rassekh R, Yip S, Northcott P, Singh SK, Dunham C, Dunn SE. Personalizing the treatment of pediatric medulloblastoma: Polo-like kinase PLK1 as a molecular target in high-risk children. Cancer Res. 2013 Sep 9. [Epub ahead of print]. PMID: 24019381

Pambid MR, Berns R, Adomat HA, Hu Kaiji, Triscott J, Maurer N, Zisman N, Ramaswamy V, Hawkins CE, Taylor MD, Dunham C, Guns E, and Dunn SE. Overcoming resistance to sonic hedgehog inhibition by targeting p90 ribosomal s6 kinase in pediatric medulloblastoma. Pediatr Blood Cancer. 2013 Aug 12. doi: 10.1002/pbc.24675. [Epub ahead of print]. PMID: 23940083

Reipas KM, Law JH, Coute N, Islam S, Li Y, Li H, Cherkasov A, Jung K, Cheema AS, Jones SJM, Hassell JA, and Dunn SE. Luteolin is a novel p90 ribosomal S6 kinase (RSK) inhibitor that suppresses Notch4 signaling by blocking the activation of Y-box binding protein-1 (YB-1). Oncotarget. 2013 Feb;4(2):329-45. PMID: 23593654

Triscott J, Lee C, Hu K, Fotovati A, Berns R, Pambid M, Luk M, Kast RE, Kong E, Toyota E, Yip S, Toyota B, and Dunn SE. Disulfiram, a drug widely used to control alcoholism, suppresses the self-renewal of glioblastoma and over-rides resistance to temozolomide. Oncotarget. Oct 8, 2012. PMID: 23047041

Stratford AL*, Reipas K*, Hu K, Fotovati A, Brough R, Frankum J, Takhar M, Watson P, Ashworth A, Lord CJ, Lasham A, Print CG, and Dunn SE. Targeting p90 Ribosomal S6 Kinase Eliminates Tumor-Initiating Cells by Inactivating Y-Box Binding Protein-1 in Triple-Negative Breast Cancers. Stem Cells, 30(7):1338-48. July 2012. *Equal contributions. PMID: 22674792

Lee C, Fotovati A, Triscott J, Chen J, Venugopal C, Singhal A, Dunham C, Kerr JM, Verreault M, Yip S, Wakimoto H, Jones C, Jayanthan A, Narendran A, Singh SK, and Dunn SE. Polo-Like Kinase 1 (PLK1) Inhibition Kills Glioblastoma Multiforme Brain Tumour Cells in Part Through Loss of SOX2 and Delays Tumour Progression in Mice. Stem Cells, 30(6):1064-75. June 2012. PMID: 22415968

Hu K, Law J, Fotovati A, and Dunn SE. Small interfering RNA library screen identified polo-like kinase-1 (PLK1) as a potential therapeutic target for breast cancer that uniquely eliminates tumour-initiating cells. Breast Cancer Research 14:R22. 2012. PMID: 22309939

Astanehe A, Finkbeiner MR, Krzywinski M, Fotovati A, Dhillon J, Berquin IM, Mills GB, Marra MA, and Dunn SE. MKNK1 is a YB-1 target gene responsible for imparting trastuzumab resistance and can be blocked by RSK inhibition. Oncogene. 2012 Jan 16. PMID: 22249268

Fotovati A, Abu-Ali S, Wang PS, Deleyrolle LP, Lee C, Triscott J, Chen JY, Franciosi S, Nakamura Y, Sugita Y, Uchiumi T, Kuwano M, Leavitt BR, Singh SK, Jury A, Jones C, Wakimoto H, Reynolds BA, Pallen CJ, and Dunn SE. YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth. Cancer Res. 71(16):5569-78. 2011. PMID: 21730024

Law JH, Li Y, To K, Wang M, Astanehe A, Lambie K, Dhillon J, Jones SJ, Gleave ME, Eaves CJ, and Dunn SE. Molecular decoy to the Y-box binding protein-1 suppresses the growth of breast and prostate cancer cells whilst sparing normal cell viability. PLoS One. 2010. 5 (9). 2010. PMID: 20844753

To K, Fotovati A, Reipas KM, Law JH, Hu K, Wang J, Astanehe A, Davies AH, Lee L, Stratford AL, Raouf A, Johnson P, Berquin IM, Royer HD, Eaves CJ, and Dunn SE. Y-box binding protein-1 induces the expression of CD44 and CD49f leading to enhanced self-renewal, mammosphere growth, and drug resistance. Cancer Res. 70(7): 2840-51. 2010. PMID: 20332234

Gao Y, Fotovati A, Lee C, Wang M, Cote G, Guns E, Toyota B, Faury D, Jabado N, and Dunn SE. Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide independent O6-methylguanine-DNA methyltransferase. Mol Cancer Ther. 8(12):3276-84. 2009. PMID: 19996271

Hu K, Lee C, Qiu D, Fotovati A, Davies A, Abu-Ali S, Wai D, Lawlor ER, Triche TJ, Pallen CJ, and Dunn SE. Small interfering RNA library screen of human kinases and phosphatases identifies polo-like kinase 1 as a promising new target for the treatment of pediatric rhabdomyosarcomas. Mol Cancer Ther. 8(11):3024-35. 2009. PMID: 19887553


Grants
Michael Cuccione Childhood Cancer Research Program Brain Tumour Grant - Project: “Personalizing the treatment of pediatric medulloblastoma”

Funding Support:
Hannah’s Heroes Foundation
Summits of Hope
Honours & Awards
Research Group Members
  • Dr. Anna Stratford (PhD) – Research Associate
  • Dr. Abbas Fotovati (PhD) – Research Associate
  • Dr. Kaiji Hu (PhD) – Senior Lab Technician/High Content Screen Coordinator
  • Mary Pambid (MSc) – Lab Technician
  • Rachel Berns (BSc) – Lab Technician
  • Joanna Triscott – PhD Graduate Student
  • Natalie Firmino – MSc Graduate Student
  • Marcus Green – UK Medical Student, Research Intern
  • Brenda Tse (MSc) – Research Coordinator

Clinical collaborators: BC Children’s Hospital: Neurosurgical, Neuropathology, Hematology/Oncology; BrainCare BC

Current Openings: Postdoctoral fellows, top-ranking PhD candidates