Pharmaceutical and Biomedical Sciences
Associate Professor
Graduate Coordinator
Interim Assistant Department Head for Graduate Education

Pharmaceutical and Biomedical Sciences


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

Areas of Expertise

Research Areas: Impact of vitamin B1 on cancer progression
Opportunities for Collaboration:  Techniques or expertise found in another lab

Honors, Awards, and Achievements

Named the College of Pharmacy “Teacher of the Year” for 2017

Research Interests

Primary research interests surround the pathophysiological implications of Vitamin B1 (thiamine) deficiency and supplementation. These research efforts have centered on how hypoxia inducible factor-1 alpha (HIF1α) impacts thiamine homeostasis and how changes in thiamine status can in turn regulate HIF1α responses. HIF1α is an essential adaptive stress response transcriptional factor that can contextually mediate either pro-survival or pro-death cellular responses. Research in the lab currently focuses on two projects: 1) Thiamine deficiency induced Alzheimer’s Disease (AD) neuropathology and 2) Impact of vitamin B1 supplementation on cancer progression.

Project 1: Declining vitamin B1 (thiamine) blood levels significantly correlates with a deterioration in cognitive function and is associated with promoting Alzheimer’s Disease (AD) neuropathology hallmarks. Thiamine is a critical enzyme cofactor within the glycolytic metabolism network that is fundamentally required to sustain the bioenergetic and anabolic needs of all cells. The brain’s extensive requirement for glucose metabolism to satisfy its high energy demand makes it particularly vulnerable to thiamine insufficiency (TI) mediated metabolic impairment. A central feature for neuronal cell injury as a result of low cellular TDP levels is severe deficits in cerebral energy metabolism. Congruent with established AD pathology, TI produces cerebral energy hypometabolism, inflammation, oxidative stress, and an increase in plaque formation within the hippocampus, cortex and thalamus. Thiamine or more specifically the activated cofactor, thiamine diphosphate (TDP) ensures the function of 3 key metabolic enzymes, PDH, α-KGDH, and TKT. The activity of these thiamine dependent enzymes are significantly reduced in post-mortem Alzheimer’s patients and strongly correlate with dementia rating. Yet despite progress into the relationship between reduced thiamine levels and the neuropathology of AD, mechanistic insight is lacking. We have established that the metabolic dysfunction as a consequence of TI activates hypoxia inducible factor-1 alpha (HIF1α). Research in the lab focuses on testing the hypothesis that TI mediated metabolic activation of HIF1α initiates pro-apoptotic and amyloidogenic processes that produce the cellular and regional histological presentation of TI associated AD-neuropathology.

Project 2: Vitamin B1 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).  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 thiamine 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. 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 neurodegeneration as well as cancer are currently needed. Additional interests in biochemistry (specifically metabolism), molecular biology, nutrition, 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 utilization of various in vivo models.

Selected Publications

Maria Luisa Valle, Yasmin Tarek Anderson, Neil Grimey, and Jason Zastre. Thiamine Insufficiency induces Hypoxia Inducible Factor-1a as an upstream mediator for neurotoxicity and AD-like pathology. Molecular and Cellular Neuroscience. 2022. 123:103785

Jonus HC, Byrnes CC, Kim J, Valle ML, Bartlett MG, Said HM, Zastre JA. Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy. Biomed Pharmacother. 2020 Jan; 121

Kim J, Jonus HC, Zastre JA, Bartlett MG. Development of an IPRP-LC-MS/MS method to determine the fate of intracellular thiamine in cancer cells. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Aug 15;1124:247-255

Jonus HC, Hanberry BS, Khatu S, Kim J, Luesch H, Dang LH, Bartlett MG, Zastre JA. The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions. Oncotarget, 2018. 9 (83):35422-35438.

Zera, K. and J. Zastre (2018). Stabilization of the hypoxia-inducible factor-1 alpha in thiamine deficiency is mediated by pyruvate accumulation. Toxicol Appl Pharmacol.355:180-188.

Zera and J. Zastre. Thiamine deficiency activates hypoxia inducible factor-1alpha to facilitate pro-apoptotic responses in mouse primary astrocytes. Plos One. 12 (10): e0186707 (2017).

Grant Support


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