Jason Zastre, Ph.D.
Pharmaceutical and Biomedical Sciences
|B. Sc. Pharmacy||University of Manitoba||Canada||1994|
|M. Sc. Pharmacy||University of Manitoba||Canada||1998|
|Ph.D.||University of British Columbia||Canada||2004|
- Post-doctoral Experience
- Postdoctoral Fellow 2004-2005, BC Cancer Research Center, Advanced Therapeutics, Vancouver, BC Canada
Postdoctoral Fellow 2005-2007, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON Canada
- Honors and Awards
- Postdoctoral Fellowship Award, CIHR-Rx&D, 2005
- Research Interests
- The movement of drug across cell membranes is an essential process that can dictate the efficacy, elimination and toxicity of all drugs. This process is mediated through passive diffusion or facilitated/active transport mechanisms involving membrane associated transporters. Transporters involved in the absorption, distribution, and elimination of drugs belong to the ATP Binding Cassette (ATP) and the Solute Carrier (SLC) super-family. In the body, ABC and SLC transporters function in the homeostatic regulation of many endogenous substrates, such as steroidal hormones, bile salts, and metabolic products such as bilirubin and oxysterols. Both ABC and SLC transporters are extensively expressed in various tissues responsible for drug elimination (liver and kidney) and barrier tissues such as the intestinal tract, blood-CSF and the blood brain barrier. Drug interactions with transporters in these tissues can i) impact efficacy by regulating drug entry into the body and cellular uptake at target sites; ii) facilitate drug elimination from the body; iii) contribute to adverse drug reactions and toxicities via competition with co-administered xenobiotics or endogenous substrates (endobiotics).
Using a multi-disciplinary approach encompassing knowledge and techniques from molecular biology, pharmacokinetics, biochemistry, protein chemistry, and pharmaceutics, my laboratory focuses on two main research pursuits pertaining to drug transport:
1. Understanding the role of transporters in mediating adverse drug reactions and toxicities as a result of drug-endobiotic and drug-drug interactions.
2. Understanding the transcriptional regulation and changes in transporter function as a result of disease state and the long term usage of drugs.
Currently, our research interest is in understanding drug transport and transporter expression within poly-pharmacy drug regimens used for the treatment of HIV/AIDS, cancer and cardiovascular disease. Using a combination of in vivo and in vitro model systems, our intent is to demonstrate the clinical impact of drug-drug and drug-endobiotic transport interactions and changes in transporter expression and function in the disease itself and with the chronic administration of poly-pharmacy regimens. This knowledge will allow for improved guidelines for co-administration of drugs and provide insight into transport processes that can facilitate drug absorption, distribution, and elimination as well as mediate adverse drug reactions and toxicity.
- Representative Publications
- J. Zastre, J. Jackson, W. Wong, and H. Burt. Methoxypolyethylene glycol-block-polycaprolactone diblock copolymers reduce P-glycoprotein efflux in the absence of a membrane fluidization effect while stimulating P-glycoprotein ATPase activity. Journal of Pharmaceutical Sciences. 96:864-875 (2007)
J. Zastre, E. Ramsay, M. Anantha, and M, Bally. Irinotecan-cisplatin interactions assessed in cell based screening assays: cytotoxicity, drug accumulation and DNA adduct formation in an NSCLC cell line. Cancer Chemotherapy and Pharmacology. 60:91-102 (2007)
D. Waterhouse, K. Gelmon, R. Klasa, K. Chi, D. Huntsman, E. Ramsay, E. Wasan, L. Edwards, C. Tucker, J. Zastre, Y. Zhang, D. Yapp, V. Dragowska, S. Dunn, S. Dedhar, and M. Bally. Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers. Current Cancer Drug Targets 6:455-489 (2006)
J. Zastre, J. Jackson, and H. Burt. Evidence for modulation of P-glycoprotein mediated efflux by methoxypolyethylene glycol-block-polycaprolactone amphiphilic diblock copolymers. Pharmaceutical Research 21:1489-1497 (2004)
K. Letchford, J. Zastre, R. Liggins, and H. Burt. Synthesis and characterization of short block length methoxypoly(ethylene glycol)-block-poly(caprolactone) diblock copolymers as micellar drug delivery systems. Colloids and Surfaces B: Biointerfaces 35:81-91 (2004)