Experimental Oncology

David Murray

Experimental Oncology
Department of Oncology
5-142L Katz Group Centre
114 Street & 87 Avenue
Edmonton, Alberta, T6G 2E1
Tel: 780.248.1208


Cellular and Tissue/Tumor Responses to DNA-damaging Anti-cancer Agents
The research in my laboratory focuses on understanding the basic mechanisms by which mammalian cells and intact tissues/tumors respond to ionizing radiation and DNA-damaging anticancer drugs, with an emphasis on DNA-repair pathways. My major area of translational research interest is in identifying the genetic factors (polymorphisms) that determine the extreme response of some cancer patients to anticancer therapeutics such as radiation therapy and chemotherapy.
Research Interests


The research in my laboratory focuses on understanding the basic mechanisms by which mammalian cells respond to DNA-damaging drugs, with an emphasis on DNA-repair pathways. A major area of interest is in identifying the relationships between the DNA-repair capability of cells and their ability to respond to radiation/oxidative stress under various environmental conditions (such as altered oxygenation levels typical of many tumor cells). Our studies frequently employ either mutant cell lines in which a particular DNA-repair gene is inactive or wild-type cells treated with pharmacologic or genetic inhibitors of various key damage-response proteins. We are particularly interested in how alterations in cellular pathways such as the p53/p21WAF1 axis that is involved in the cellular response to DNA damage, and that is somehow altered/mutated in most human cancers, might be exploited to make these therapies more specific for cancer cells. Our ultimate goal is to understand the factors that govern tumor versus normal tissue radiosensitivity and to exploit these differences for therapeutic benefit.
We are also trying to understand the genetic factors (especially single nucleotide polymorphisms or "SNPs") that underlie the extreme normal-tissue responses of some cancer patients to anticancer therapeutic modalities such as radiation therapy and chemotherapy. Along with various clinical staff at the Cross Cancer Institute (Drs. Bassam Abdulkarim, Diane Severin and Matthew Parliament in Radiation Oncology, Dr. Tony Reiman in Medical Oncology) and in collaboration with the Polyomx program we are also exploring how genetic pre-screening of cancer patients (particularly with respect to the identification of SNPs in key genes such as DNA repair genes) might avoid administering treatments that could cause severe side effects in normal tissues. With members of the Oncologic Imaging division (Drs. Sandy McEwan and John Mercer) we are examining the relevance of novel cancer-imaging methodologies for evaluating early tumor responses to therapy.



Mirzayans R, Scott A, Pollock S, Andrais B, Murray D. Induction of accelerated senescence by g radiation in human solid tumor-derived cell lines expressing wild-type TP53. Radiat Res 163, 53-62, 2005.

Barker S, Weinfeld M, Zheng J, Li L, Murray D. The identification of mammalian proteins crosslinked to DNA by ionizing radiation. J Biol Chem 280, 33826-33838, 2005.

Damaraju S, Murray D, Dufour J, Carandang D, Myrehaug S, Fallone G, Field C, Greiner R, Hanson J, Cass CE, Parliament M. Association of DNA repair and steroid metabolism gene polymorphisms with clinical late toxicity in patients treated with conformal radiotherapy for prostate cancer. Clin Cancer Res 12, 2545-2554, 2006.

Murray D, Wang JYJ, Mirzayans R. DNA repair after low doses of ionising radiation. Int J Low Radiat 3, 255-272, 2006.

Mirzayans R, Severin D, Murray D. Relationship between DNA double strand break rejoining and cell survival following exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: implications for the evaluation of clinical radiosensitivity. Int J Radiat Oncol Biol Phys 66, 1498-1505, 2006.

Murray D, McEwan AJ. Radiobiology of systemic radiation therapy. Cancer Biother Radiopharm, Vol. 22, No. 1: 1-23, 2007.

Mirzayans R, Murray D. Cellular Senescence: Implications for Cancer Therapy. In: “New Research on Cell Aging”. Edited by RB Garvey, Nova Science Publishers, Inc., Hauppauge, New York, pp. 1-64, 2007.

Murray D, Mirzayans R. Role of p53 in the repair of ionizing radiation-induced DNA damage. In: “New Research on DNA Repair”. Edited by BR Landseer, Nova Science Publishers, Inc., Hauppauge, New York, pp. 325-373, 2007.

Mirzayans R, Scott A, Andrais B, Pollock S and Murray D. Ultraviolet light exposure triggers nuclear accumulation of p21WF1 and accelerated senescence in human normal and nucleotide excision repair-deficient fibroblast strains. J Cell Physiol, Sept 25 [Epub ahead of print], 2007.