Robert Prosser

About the Scientist

E-mail:	obains@alumni.sfu.ca
Phone:	(604)827-3347, (604)822-3382

Training

Degree:	Masers of Environmental Toxicology (M.E.T.)
Institution:	Department of Biological Sciences, Simon Fraser University
Period:	Sept 2001 – May 2004

Degree:	Certificate in Liberal Arts
Institution:	Faculty of Arts and Social Sciences, Simon Fraser University
Period:	Jan 2001 – Feb 2002

Degree:	Minor in Criminology
Institution:	School of Criminology, Simon Fraser University
Period:	Jan 1999 - May 2001

Degree:	B.Sc. (Animal Physiology)
Institution:	Department of Biological Sciences, Simon Fraser University
Period:	Sept 1996 – May 2001

Current Position

Position:	Ph.D. candidate
Research Group:	Faculty of Pharmaceutical Sciences, University of British Columbia, Sept 2005 – current
Supervisors:	Dr. K. Wayne Riggs and Dr. Ronald E. Reid

Scholarships + Awards

Name:	CIHR Doctoral Research Award
Organization:	Canadian Institutes of Health Research
Period:	Sept 2007 - Aug 2010

Name:	Graduate Student Outstanding Service Award
Organization:	Faculty of Pharmaceutical Sciences
Period:	2008

Name:	Graduate Student Travel Award in Pharmaceutical Sciences
Organization:	Faculty of Pharmaceutical Sciences
Tenure period:	Mar 2008

Name:	Pacific Century Scholarship
Organization:	University of British Columbia
Tenure period:	Sept 2007 – Aug 2009 (declined due to receiving the CIHR Doctoral Research Award)

Name:	University Graduate Fellowship
Organization:	The University of British Columbia
Tenure period:	Sept 2006 – Aug 2007

Name:	Ph.D. Tuition Fee Award
Organization:	The University of British Columbia
Tenure period:	Sept 2007 – Aug 2008 Sept 2006 – Aug 2007 Sept 2005 – Aug 2006

Name:	Graduate Entrance Scholarship
Organization:	University of British Columbia
Tenure period:	Sept 2005 – Dec 2005
Value:	$1797

Name:	Teaching Assistant Award for 2002-2003
Organization:	Department of Biological Sciences
Value:	$100

About The Research

Altered metabolism of anthracyclines by naturally occurring variants of human carbonyl reductases and aldo-keto reductases.

Aldo-keto reductases (AKRs) and carbonyl reductases (CBRs) are of particular interest clinically as they play a major role in metabolism of the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). These two drugs are the most widely used anthracyclines in oncological practice. DOX is a vital component in the treatment of non-Hodgkin’s lymphoma, childhood solid tumors, soft tissue carcinomas, and breast cancer, while DAUN occupies a central position in treating acute leukemias.

Even though DAUN and DOX-based chemotherapies have contributed to improved life expectancy, both have been linked to the development of serious life-threatening adverse events with a high patient variability. A prominent example is chronic cardiotoxicity, which can ultimately lead to irreversible complications such as congestive heart failure, a life long threat with a mortality rate that can exceed 10% in children treated with ≥300 mg/m2 of any anthracycline and 26% in adults treated with ≥550 mg/m2 DOX. Both the frequency of chronic cardiotoxicity and mortality rate are associated with increased dosage of the anthracyclines along with the concurrent use of other anticancer drugs, such as herceptin, paclitaxel and cyclophosphamide.

The underlying cause(s) of interpatient variation in DAUN or DOX induced adverse drug events may be due to altered enzyme activity associated with non-synonymous nucleotide polymorphisms (ns-SNPs) of the AKR and CBR genes. It is known that ns-SNPs are relevant to the prediction of disease development and selection of therapy, thereby impacting the treatment and/or development of several different forms of cancer. Metabolic differences seen with the mutant enzymes compared with that of the wild-type may suggest that the ns-SNPs are suitable biomarkers in assessing the bioavailability of DOX or DAUN in cancer patients before treatment.

Publications + Presentations

Published Papers

Bains, O.S., Karkling M.J., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. (2009) Two non-synonymous single nucleotide polymorphisms of carbonyl reductase 1 demonstrate reduced in vitro metabolism of daunorubicin and doxorubicin. Drug Metabolism and Disposition. 37: 1107-1114. (Ph.D. work)
Bains, O.S., Takahashi, R.H., Pfeifer, T.A., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. (2008) Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in vitro metabolism of daunorubicin. Drug Metabolism and Disposition. 36(5): 904-910. (Ph.D. work)
Takahashi, R.H., Bains, O.S., Pfeifer, T.A., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. (2008) Aldo-keto reductase 1C2 fails to metabolize doxorubicin and daunorubicin in vitro. Drug Metabolism and Disposition. 36(6): 991-994. (Ph.D. work)
Hildebrand, J.L., Bains, O.S., Lee, D.S.H., and Kennedy, C.J. (2009) Functional and energetic characterization of P-gp-mediated doxorubicin transport in rainbow trout (Oncorhynchus mykiss) hepatocytes. Comparative Biochemistry and Physiology Part C: Toxicology and Pharmacology. 149(1): 65-72. (Collaborative research)
Lizardo-Daudt, H.M., Bains, O.S., Singh, C.R., and Kennedy, C.J. (2007) Cadmium chloride-induced disruption of testicular steroidogenesis in rainbow trout. Archives of Environmental Contamination and Toxicology. 55(1): 103-110. (Collaborative research)
Lizardo-Daudt, H.M., Bains, O.S., Singh, C.R., and Kennedy, C.J. (2007) Biosynthetic capacity of rainbow trout (Oncorhynchus mykiss) interrenal tissue following cadmium exposure. Archives for Environmental Contamination and Toxicology. 52(1): 90-96. (Collaborative research)
Bains, O.S., and Kennedy, C.J. (2005) Alterations in respiration rates of isolated rainbow trout hepatocytes exposed to the P-glycoprotein substrate Rhodamine 123. Toxicology. 214(1-2): 87-98. (Research Assistant work) 8. Bains, O.S., and Kennedy, C.J. (2004) Energetic costs of pyrene metabolism in isolated hepatocytes of rainbow trout, Oncorhynchus mykiss. Aquatic Toxicology. 67(3): 217-226. (Masters work)

Accepted Papers

Bains, O.S., Karkling, M.J., Lubieniecka, J.M., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. (2009) Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. Journal of Pharmacology and Experimental Therapeutics. (Ph.D. work)

Conference presentations

Bains, O.S., Karkling, M.J., Lubieniecka, J.M, Grigliatti, T.A., Reid, R.E., and Riggs, K.W. Naturally occurring variants of human CBR3 alter anthracycline in vitro metabolism. American Association of Pharmaceutical Scientists Annual Meeting and Exposition, Los Angeles, CA., Nov 8-12 2009.
Bains, O.S., Karkling, M.J., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. A non-synonymous single nucleotide polymorphism of carbonyl reductase 1 exhibits reduced in vitro metabolism of daunorubicin and doxorubicin. 15th North American Regional ISSX Meeting, San Diego, CA., Oct 12-16 2008.
Bains, O.S., Takahashi, R.H., Pfeifer, T.A., Grigliatti, T.A., Reid, R.E., and Riggs, K.W. Two allelic variants of aldo-keto reductase 1A1 exhibit reduced in vitro metabolism of daunorubicin. 9th World Conference on Clinical Pharmacology and Therapeutics, Québec City, QC., Jul 27-Aug 1 2008.
Kennedy, C.J., Hildebrand, J.L., Bains, O.S., and Lee, D.H.S. Functional and energetic characterization of P-glycoprotein-mediated efflux of xenobiotics in teleosts. 8th International Congress on the Biology of Fish, Portland, OR., Jul 28-Aug 1 2008.

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