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The Washington Research Foundation Fellowship

Michael Choi, Biochemistry, 2011-12 WRFF

Michael Choi photoMichael Choi is very interested in biological and biochemical research especially with applications towards medicine and helping patients. Since his freshman year, he has been investigating embryonic stem cells and stem cell maintenance in the Ruohola-Baker laboratory, focusing on the metabolism of embryonic stem cells and how it relates to their function. Stem cells play a critical role in development and disease; by better understanding how these cells function in both normal and pathological conditions, scientists can learn how to control, treat, and cure disorders that arise. His undergraduate research experience and his majors in biochemistry and chemistry with a minor in mathematics have convinced him to pursue a career in science with applications towards medicine. In the future, he is interested in attending graduate school and plans to further investigate the biology of disease and research cures from a biochemical, chemical, and mathematical perspective.

Mentor: Hannele Ruohola-Baker, Biochemistry

Project Title: Characterizing the Metabolism of Embryonic Stem Cells

Abstract: Embryonic stem cells are isolated from the early developing embryo and are capable of forming all of the different cell types found in the body. Understanding how these cells develop and maintain their specialized state is critical to understanding how these cells function. We hypothesize that embryonic stem cells acquire a unique metabolic state that aids them in maintaining their specialized state. Using both mouse and human embryonic stem cells, we investigated their metabolism and how the metabolism changed through different stages of early embryonic development. The metabolic state was characterized by quantifying mitochondria DNA copy number, intracellular adenosine triphosphate levels, and oxygen consumption rates and extracellular acidification rates by a Seahorse Bioanalyzer XF apparatus. We found that later embryonic stem cells compared to early embryonic stem cells utilize much less oxygen and have a much more glycolytic metabolic phenotype despite a greater level of mitochondrial DNA copy numbers. Furthermore, using quantitative polymerase chain reaction experiments, we found that genes key to regulating glycolysis such as lactate dehydrogenase, pyruvate dehydrogenase kinase, and liver glycogen phosphorylase are significantly upregulated in later embryonic stem cells. The metabolic transition between early and later embryonic stem cells may be due to the activity of hypoxia inducible factor 1a (HIF1a), a known key regulator of these glycolytic genes. We show that the overexpression of HIF1a in embryonic stem cells is able to shift the cells towards a more glycolytic metabolic state. Overall, these results indicate that late embryonic stem cells have an increased glycolytic phenotype and that HIF1 is an important regulator of the metabolism of embryonic stem cells.