Skip to content. | Skip to navigation


Personal tools

Kevin L. Bennewith

Department of Integrative Oncology - Radiation Biology Unit


Scientist

kbennewi@bccrc.ca    Rm. 10-108 • 675 West 10th Avenue, Vancouver, BC, Canada V5Z 1L3

Tel.  604 675 8042    Lab. 604 675 8000 x7041 

KB small


Current Appointments

Scientist, Department of Integrative Oncology, Radiation Biology Unit, BC Cancer Agency (2011)

Assistant Professor, Department of Pathology and Laboratory Medicine, University of British Columbia (2011)  http://pathology.ubc.ca/faculty/kevin-bennewith/

Faculty Associate Member, Interdisciplinary Oncology Program, Faculty of Graduate and Postdoctoral Studies, UBC

Previous Appointments and Education

Clinical Assistant Professor, Department of Pathology and Laboratory Medicine, UBC (2009-2011)

Research Scientist, Department of Integrative Oncology, BC Cancer Agency (2008-2011)

Post-Doctoral Scholar, Division of Radiation and Cancer Biology, Stanford University (2004-2008)

PhD, Department of Pathology and Laboratory Medicine, UBC (1999-2004)

BSc, Department of Chemistry, UBC (1993-1997)


GROUP MEMBERS

Dr. Kevin L. Bennewith, PhD - Principal Investigator

Staff

Nancy E. LePard - Research Assistant

Trainees

Dr. Melisa J. Hamilton, PhD - Post-Doctoral Fellow

Jenna L. Collier - MSc Student

Natalie Firmino - PhD Student

Elizabeth C. Halvorsen - PhD Candidate

Brennan J. Wadsworth - PhD Student

Ada Young - MSc Student

Alumni

Dr. Judit P. Banath, PhD - Research Assistant

Momir Bosiljcic - Technician; MSc Student; CIHR Canada Graduate Scholarships Master's Award recipient; Research Assistant

Bryant T. Harbourne - MSc Student

Jessica X. Jia - Technician

Ada Y. Kim - MSc Student; Summer Student; Canadian Breast Cancer Foundation (BC/Yukon) Studentship Award recipient; Undergraduate Honour's Thesis Student

Martin Koehler - MSc Student

Patrick Lai - Medical Summer Student; Canadian Breast Cancer Foundation (BC/Yukon) Studentship Award recipient

Hannah Lee - Undergraduate Honour's Thesis Student; Summer Student;  Canadian Breast Cancer Foundation (BC/Yukon) Studentship Award recipient

Dr. Sahar Mahmoud, MD, PhD - Post-Doctoral Fellow

Rose Shumiatcher - Undergraduate Summer Student; BC Cancer Foundation Studentship Award recipient

G.R. Tom Walton - Medical Summer Student; UBC Faculty of Medicine Summer Student Research Program Award recipient 


RESEARCH INTERESTS

Most solid tumours contain cells that are poorly oxygenated, and these hypoxic tumour cells are refractory to a variety of cancer treatments including radiation therapy and chemotherapy.  Not only are hypoxic cells the most difficult tumour cells to kill with conventional therapies, but hypoxia also promotes a more aggressive tumour phenotype. In the clinic, patients with primary tumours that contain large fractions of hypoxic cells have poor outcome, due in large part to limited treatment response and the presence of distant metastatic disease. My lab is interested in the role of tumour hypoxia (and the tumour microenvironment) in cancer therapy and in the development of tumour metastases.

Quantification of Tumour Hypoxia

The extent of hypoxia in solid tumours can be measured by exogenous hypoxia markers (drugs that are bound and retained in hypoxic cells) and/or endogenous hypoxia markers (proteins that are increased in hypoxic cells).  The oxygenation level of tumour cells can change as a function of time, and this transient (or cyclic) hypoxia is poorly understood.  We use immunohistochemistry and flow cytometry to identify and quantify transiently hypoxic tumour cells with the goal of designing more effective therapeutic strategies to target (or exploit) tumour hypoxia.

Bone marrow-derived cells in solid tumour metastasis

The metastatic spread of cancer is associated with over 90% of cancer-related deaths.  We have found that selected proteins secreted by tumours can stimulate the accumulation of bone marrow-derived cells (BMDCs) in tissues prior to the arrival of metastatic tumour cells.  BMDC accumulation may enhance the survival and growth of metastatic tumour cells, and predict future sites of metastatic tumour growth.  We are particularly interested in the accumulation and function of immune suppressive myeloid cells (myeloid-derived suppressor cells, macrophages) in metastatic target organs, and in therapeutic modification of tumour-secreted proteins and immune suppressive cells in metastatic-target organs to decrease metastatic tumour growth. 


FUNDING

We gratefully acknowledge operating grant funding and stipend support from the following organizations:

Operating funds:

The Canadian Institutes of Health Research (http://www.cihr.gc.ca/e/193.html)

The BC Cancer Foundation (http://www.bccancerfoundation.com/)

The Canadian Institutes of Health Research: Institute of Cancer Research (http://www.cihr-irsc.gc.ca/e/12506.html)

The Terry Fox Foundation (http://www.terryfox.orgvia The Canadian Cancer Society Research Institute (http://cancer.ca/Research.aspx)

Stipend and salary support:

Kevin Bennewith is a Michael Smith Foundation for Health Research Biomedical Research Scholar (http://www.msfhr.org/)

Melisa Hamilton is funded by a Canadian Breast Cancer Foundation BC/Yukon Division Post-Doctoral Fellowship (http://www.cbcf.org/bc)

Jenna Collier is funded by a Frederick Banting and Charles Best Canada Graduate Scholarships Master's Award from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca)

Liz Halvorsen was funded by a Frederick Banting and Charles Best Canada Graduate Scholarships Master's Award from the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca)

Liz Halvorsen is currently funded by a Four Year Doctoral Fellowship from the University of British Columbia (https://www.grad.ubc.ca/awards/four-year-doctoral-fellowship-4yf)

Brennan Wadsworth was funded by an Alexander Graham Bell Canada Graduate Scholarship Master's Award from the National Sciences and Engineering Research Council of Canada (http://www.nserc-crsng.gc.ca/index_eng.asp)

Brennan Wadsworth is currently funded by a Northern Telecom Graduate Fellowship and a Jean MacDonald Graduate Fellowship from the University of British Columbia Affiliated Fellowship Program (https://www.grad.ubc.ca/awards/affiliated-fellowships)

Brennan Wadsworth is a Scholar in The Terry Fox Foundation Strategic Initiative for Excellence in Radiation Research for the 21st Century (EIRR21) at CIHR (http://www.eirr21.utoronto.ca/)

 


SELECTED PUBLICATIONS

  1. Halvorsen EC, Hamilton MJ, Young A, Wadsworth BJ, LePard NE, Lee HN, Firmino N, Collier JL and Bennewith KL.  Maraviroc decreases CCL8-mediated migration of CCR5+ regulatory T cells and reduces metastatic tumour growth in the lungs.  Oncoimmunology (in press), 2016.

  2. Krystal G, Hamilton MJ and Bennewith KL.  SHIP prevents metastasis.  Aging [Epub ahead of print], 2016. http://www.ncbi.nlm.nih.gov/pubmed/27208543

  3. Firmino N*, Martinez VD*, Rowbotham DA, Enfield KSS, Bennewith KL and Lam WL. HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer.  [*Co-first author] Oral Oncology 55:43-8, 2016. http://www.ncbi.nlm.nih.gov/pubmed/26852287

  4. Hamilton MJ, Halvorsen EC, LePard NE, Bosiljcic M, Ho V, Lam V, Banáth JP, Bennewith*+ KL and Krystal* G. SHIP represses lung inflammation and inhibits mammary tumor metastasis in BALB/c mice. [*Co-senior author; +corresponding author] Oncotarget 7(4): 3677-91, 2016. http://www.ncbi.nlm.nih.gov/pubmed/26683227
  5. Conway EM, Pikor LA, Kung S, Hamilton MJ, Lam S, Lam* WL and Bennewith*+ KL. Macrophages, inflammation, and lung cancer. [*Co-senior author; +corresponding author] Am J Resp Crit Care (ePub ahead of print), 2015.  http://www.ncbi.nlm.nih.gov/pubmed/26583808
  6. El-Naggar AM, Veinotte CJ, Cheng H, Grunewald TG, Negri GL, Somasekharan SP, Corkery DP, Tirode F, Mathers J, Khan D, Kyle AH, Baker JH, LePard NE, McKinney S, Hajee S, Bosiljcic M, Leprivier G, Tognon CE, Minchinton AI, Bennewith KL, Delattre O, Wang Y, Dellaire G, Berman JN, Sorensen PH. Translational activation of HIF1α by YB-1 promotes sarcoma metastasis. Cancer Cell 27(5): 682-97, 2015. http://www.ncbi.nlm.nih.gov/pubmed/25965573
  7. Chafe SC, Lou Y, Sceneay J, Vallejo M, Hamilton MJ, McDonald PC, Bennewith KL, Möller A and Dedhar S. Carbonic Anhydrase IX promotes myeloid-derived suppressor cell mobilization and establishment of a metastatic niche by stimulating G-CSF production. Cancer Res 75(6): 996-1008, 2015. http://www.ncbi.nlm.nih.gov/pubmed/25623234
  8. Cochrane DR, Lin D, Dellaire G, Halvorsen EC, Berman JN, Wang Y, Huntsman DG and Bennewith KL. Animal models of metastasis, in Genomic Instability and Cancer Metastasis, Maxwell CA and Roskelley CD ed., Springer, 2015.

  9. Halvorsen EC, Mahmoud SM and Bennewith KL. Emerging roles of regulatory T cells in tumour progression and metastasis. Cancer Metastasis Rev 33(4): 1025-41, 2014. http://www.ncbi.nlm.nih.gov/pubmed/25359584
  10. Rowbotham D, Enfield KSS, Martinez VD, Thu KL, Vucic EA, Stewart GL, Bennewith KL and Lam WL. Multiple components of the VHL tumor suppressor complex are frequently affected by DNA copy number loss in pheochromocytoma. Int J Endocrinology doi: 10.1155/2014/546347, 2014. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/25298778
  11. Ho VW, Hamilton MJ, Dang NH, Hsu BE, Adomat HH, Guns ES, Weljie A, Samudio I, Bennewith KL and Krystal G.  A low carbohydrate, high protein diet combined with celecoxib markedly reduces metastasis. Carcinogenesis 35(10): 2291-9, 2014. http://www.ncbi.nlm.nih.gov/pubmed/25023988
  12. Hamilton MJ, Bosiljcic M, Lepard NE, Halvorsen EC, Ho VW, Banáth JP, Krystal G, Bennewith KL. Macrophages are more potent immune suppressors ex vivo than immature myeloid-derived suppressor cells induced by metastatic murine mammary carcinomas. J Immunol. 192(1):512-22, 2014. http://www.ncbi.nlm.nih.gov/pubmed/24285836
  13. Wilson IM, Vucic EA, Enfield KS, Thu KL, Zhang YA, Chari R, Lockwood WW, Radulovich N, Starczynowski DT, Banáth JP, Zhang M, Pusic A, Fuller M, Lonergan KM, Rowbotham D, Yee J, English JC, Buys TP, Selamat SA, Laird-Offringa IA, Liu P, Anderson M, You M, Tsao MS, Brown CJ, Bennewith KL, Macaulay CE, Karsan A, Gazdar AF, Lam S, Lam WL. EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk. Oncogene. 2013 Oct 7. doi: 10.1038/onc.2013.396. [Epub ahead of print]. http://www.ncbi.nlm.nih.gov/pubmed/24096489

  14. Hamilton MJ, Banath JP, Lam V, LePard NE, Krystal G, Bennewith KL. Serum inhibits the immunosuppressive function of myeloid-derived suppressor cells isolated from 4T1 tumor-bearing mice. Cancer Immunol Immunother. 61(5): 643-54, 2012. http://www.ncbi.nlm.nih.gov/pubmed/22021068
  15. Bennewith KL, Dedhar S. Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer. 11: 504-9, 2011. http://www.ncbi.nlm.nih.gov/pubmed/22128892

  16. Bosiljcic M, Hamilton MJ, Banath JP, LePard NE, McDougal DC, Jia JX, Krystal G, Bennewith KL. Myeloid suppressor cells regulate the lung environment - letter. Cancer Res. 71(14): 5050-1, 2011. http://www.ncbi.nlm.nih.gov/pubmed/21750177

  17. Bennewith KL, Erler JT, Giaccia AJ. Pre-metastatic niches, in Tumor Microenvironment, Siemann DW ed., Chichester, West Sussex, UK, John Wiley & Sons Ltd., 2011.

  18. Hamilton MJ, Antignano F, von Rossum A, Boucher JL, Bennewith KL, Krystal G. TLR agonists that induce IFN-beta abrogate resident macrophage suppression of T cells. J Immunol. 185(8): 4545-53, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20844190

  19. Ho AS, Huang X, Cao H, Christman-Skieller C, Bennewith K, Le QT, Koong AC. Circulating miR-210 as a novel hypoxia marker in pancreatic cancer. Trans Oncol. 3(2): 109-13, 2010. http://www.ncbi.nlm.nih.gov/pubmed/20360935

  20. Cairns RA, Bennewith KL, Graves EE, Giaccia AJ, Chang DT, Denko NC. Pharmacologically increased tumor hypoxia can be measured by (18)F-fluoroazomycin arabinoside positron emission tomography and enhances tumor response to the hypoxic cytotoxin PR-104.  Clin Cancer Res. 15(23): 7170-4, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19920111

  21. Huang X, Ding L, Bennewith KL, Tong RT, Welford SM, Ang KK, Story M, Le QT, Giaccia AJ.  Hypoxia inducible miR-210 regulates normoxic gene expression involved in tumor initiation.  Mol Cell. 35(6): 856-67, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19782034

  22. Bennewith KL, Huang X, Ham CM, Graves EE, Erler JT, Kambham N, Feazell J, Yang GP, Koong A, Giaccia AJ. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth. Cancer Res. 69(3): 775-84, 2009. http://www.ncbi.nlm.nih.gov/pubmed/19179545

  23. Erler* JT, Bennewith* KL, Cox TR, Lang G, Bird D, Koong A, Le QT, Giaccia AJ. Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the pre-metastatic niche. Cancer Cell. 15(1): 35-44, 2009. [*equal contributions] http://www.ncbi.nlm.nih.gov/pubmed/19111879

  24. Erler JT, Bennewith KL, Nicolau M, Dornhofer N, Kong C, Le QT, Chi JTA, Jeffrey SS, Giaccia AJ. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature. 440(7088): 1222-6, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16642001

  25. Dornhofer N, Spong S, Bennewith K, Salim A, Klaus S, Kambham N, Wong C, Kaper F, Sutphin P, Nacamuli R, Hockel M, Le Q, Longaker M, Yang G, Koong A, Giaccia A. Connective tissue growth factor-specific monoclonal antibody therapy inhibits pancreatic tumor growth and metastasis. Cancer Res. 66(11): 5816-27, 2006. http://www.ncbi.nlm.nih.gov/pubmed/16740721

  26. Bennewith KL, Durand RE. Quantifying transient hypoxia in human tumor xenografts by flow cytometry. Cancer Res. 64(17): 6183-9, 2004. http://www.ncbi.nlm.nih.gov/pubmed/15342403

  27. Bennewith KL, Raleigh JA, Durand RE. Orally administered pimonidazole to label hypoxic tumor cells. Cancer Res. 62(23): 6827-30, 2002. http://www.ncbi.nlm.nih.gov/pubmed/12460894

  28. Bennewith KL, Durand RE. Drug-induced alterations in tumour perfusion yield increases in tumour cell radiosensitivity. Br J Cancer. 85(10): 1577-84, 2001. http://www.ncbi.nlm.nih.gov/pubmed/11720448

 For the latest Bennewith Lab updates, follow us on Tumblr http://www.bennewithlab.tumblr.com