Jason Zastre, Ph.D. Assistant Professor Pharmaceutical and Biomedical Sciences Office: 222 R. C. Wilson Pharmacy Phone: 706.583.0290 E-mail: jzastre@rx.uga.edu

Biosketch

B. Sc. Pharmacy	University of Manitoba	Canada	1994
Research Associate	Novopharm Biotech	Winnipeg, MB	1996-1999
M. Sc. Pharmacy	University of Manitoba	Canada	1998
Ph.D.	University of British Columbia	British Columbia	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
CIHR-Rx&D Postdoctoral Fellowship Award 2005
Georgia Cancer Coalition Distinguished Scholar 2008

Research Interests
The primary focus of my research is to understand the regulation and function of membrane bound transporters belonging to the Solute Carrier (SLC) superfamily in cancer pathophysiology and as determinants for the cellular availability of chemotherapeutic drugs. My approach is to understand the changes in the expression of specific SLC transporters within tumor microenvironments as a result of tumor adaptive responses to physiological stress, such as hypoxia, and apply this knowledge directly to improving anticancer drug selectivity and efficacy. Physiologically, SLC transporters function to transport endogenous nutrients and hormones that are important for cellular proliferation and homeostasis. As a result of cell pro-survival responses, hypoxic cells may alter expression of transporters belonging to the SLC family in order to facilitate altered nutrient and growth factor requirements. However, the impact of hypoxia on the expression and function of SLC transporters and drug therapy are widely unknown. Our primary research priorities are to: i) identify expression and functional differences of SLC transporters between hypoxic and normoxic breast cancer cells. ii) Understand the transcriptional pathways regulating SLC transporter expression in hypoxia and nutrient deprivation. iii) Utilize pro-drug or combination chemotherapy strategies to improve the cellular bioavailability and cellular drug targeting to hypoxic cell phenotypes through SLC transporters. This unique and rational drug selection approach will take into consideration tumor heterogeneity and attempt to improve drug efficacy by exploiting alterations in transporter expression within tumor phenotypes which are generally resistant to conventional chemotherapy.

Representative Publications
Zastre, Jason A.; Chan, Gary N. Y.; Ronaldson, Patrick T.; Ramaswamy, Manisha; Couraud, Pierre O.; Romero, Ignacio A.; Weksler, Babette; Bendayan, Moise; Bendayan, Reina. Up-regulation of P-glycoprotein by HIV protease inhibitors in a human brain microvessel endothelial cell line. Journal of Neuroscience Research (2009), 87(4), 1023-1036.

Zastre, Jason A.; Jackson, John K.; Wong, Wesley; Burt, Helen M. P-Glycoprotein Efflux Inhibition by Amphiphilic Diblock Copolymers: Relationship between Copolymer Concentration and Substrate Hydrophobicity. Molecular Pharmaceutics (2008), 5(4), 643-653.

Ramsay, Euan; Alnajim, Jehan; Anantha, Malathi; Zastre, Jason; Yan, Hong; Webb, Murray; Waterhouse, Dawn; Bally, Marcel. A novel liposomal irinotecan formulation with significant anti-tumour activity: Use of the divalent cation ionophore A23187 and copper-containing liposomes to improve drug retention. European Journal of Pharmaceutics and Biopharmaceutics (2008), 68(3), 607-617.

Ramsay, Euan C.; Anantha, Malathi; Zastre, Jason; Meijs, Marieke; Zonderhuis, Jet; Strutt, Dita; Webb, Murray S.; Waterhouse, Dawn; Bally, Marcel B. Irinophore C: A Liposome Formulation of Irinotecan with Substantially Improved Therapeutic Efficacy against a Panel of Human Xenograft Tumors. Clinical Cancer Research (2008), 14(4), 1208-1217.

Zastre J, Ramsay E, Anantha M, Bally M. 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).