Ph.D. Pharmaceutical sciences, University of British Columbia, Vancouver, B.C.,Canada 2004
M.S. Pharmacy, University of Manitoba, Winnipeg, MB, Canada 1998
B.S. Pharmacy, University of Manitoba, Winnipeg, MB, Canada 1994
Impact of vitamin B1 supplementation on cancer progression: Vitamin B1 (thiamine) is an essential enzyme cofactor intersecting multiple metabolic pathways within the glycolytic metabolism network. Maintaining thiamine homeostasis requires the activity of two SLC transporters THTR1 and THTR2 to facilitate the intracellular uptake prior to activation into the coenzyme thiamine pyrophosphate (TPP) by thiamine pyrophosphokinase-1 (TPK1). Vitamin B1 is an essential enzyme cofactor for 3 key metabolic enzymes, pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (a-KGDH) in the tricarboxylic acid cycle (TCA), and transketolase (TKT) within the pentose phosphate pathway (PPP). In cancer, thiamine-dependent enzymes are exploited for energy production, biomass generation, and tumor growth. However, vitamin B1 supplementation has a duality of effects on cancer cell survival and proliferation. At low to moderate doses, thiamine increases cancer cell proliferation. At high doses (>75 times the RDA) no increase in tumor growth has been observed suggesting an anti-proliferative effect on cancer cells. The overall research objectives are i) characterize the differences in thiamine homeostasis between cancer and normal tissue. ii) determine the impact of vitamin B1 supplementation on cancer cell survival and metabolism. III) Develop strategies to reduce thiamin mediated effects on malignant progression. The results of this research will link dietary influences on cancer progression with alterations in the homeostatic regulation of vitamin B1. In addition the research will contribute new insight into the pro-survival and pro-apoptotic effects of a physiologically and pharmacologically important enzyme cofactor. Overall, the outcomes of this research will require a critical rethinking of the usage and composition of dietary supplements and implementation of nutritional monitoring protocols for cancer patients.
The prospective graduate student: Students with a research interest in cancer as well as diabetes, alcoholism, and obesity are currently needed. Additional interests should be in the area of biochemistry (specifically metabolism), molecular biology, pharmacology, and drug transporters.
Students can expect to gain research experience in various molecular and cell biology techniques including qRT-PCR, Western blotting, cell culture, transport assays, and in vivotumor xenografts.
- NIH – NIAAA
- American Cancer Society
M. Amaraneni, A. Sharma, J. Pang, S. Muralidhara, B. Cummings, C. White, J. Bruckner, and J. Zastre*. Plasma protein binding limits the blood brain barrier permeation of the pyrethroid, Deltamethrin. Toxicol letters. 250-251:21-28 (2016). (IF2015=3.88)
K. Zera, R. Sweet, and J. Zastre*. Role of HIF-lalpha in the hypoxia inducible expression of the thiamine transporter, SLC19A3. Gene. 595(2):212-220 (2016). (IF2015=2.319)
Babak Basiri, J. Michael Sutton, Bradley S. Hanberry, Jason A. Zastre and Michael G. Bartlett*. Ion Pair Liquid Chromatography Method for the Determination of Thiamine (Vitamin Bl) Homeostasis. Biomedical Chromatography. 30(1):35-41 (2016). (IF2015 = 1.729)
J. Kim, C. Hopper, K. Connell, P. Darkhal, J. Zastre, and M. Bartlett*. Development of a novel method for the bioanalysis of benfotiamine and sulbutiamine in cancer cells. Analytical Methods. 8:5596 (2016). (IF2015=1.915)
C. Mazur, S, Marchitti, and J. Zastre. P-glycoprotein inhibition by the agricultural pesticide propiconazole and its hydroxylated metabolites: Implications for pesticide-drug interactions. Toxicol Lett. 232(1):37-45 (2015).
R. Sweet and J. Zastre. HIF-1α mediated gene expression induced by Vitamin B1 deficiency. International Journal of Vitamin and Nutrition Research. 83(3):188-197 (2013).
B. Hanberry, R. Berger, and J. Zastre. High Dose Vitamin B1 Reduces Proliferation in Cancer Cell Lines Analogous to Dichloroacetate. Cancer Chemotherapy and Pharmacology. 73(3):585-594 (2014).
J. Zastre, C. Dowd, J. Bruckner, and A. Popovici. Intestinal Transport of Pyrethroid Insecticides Using Caco-2 cells. Toxicological Sciences. 136(2):284-293 (2013).
J. Zastre, R. Sweet, B. Hanberry, and S. Ye. Linking Vitamin B1 with Cancer Cell Metabolism. Cancer and Metabolism. 1:16 (2013)
J. Zastre, B. Hanberry, R. Sweet, C. McGinnis, K. Venuti, M. Bartlett, and R. Govindarajan. Up-Regulation of Vitamin B1 Homeostasis Genes in Breast Cancer. Journal of Nutritional Biochemistry. 24(9):1616-1624 (2013).
R. Sweet, A. Paul, and J. Zastre. Hypoxia induced up-regulation and function of the thiamine transporter, SLC19A3 in breast cancer cells. Cancer Biology and Therapy. 10(11):1101-11 (2010).
Named the College of Pharmacy “Teacher of the Year” for 2017