Catabolism of retinoic acid (RA) is an essential reaction preventing overload of RA that can be as toxic as its shortage. Cyp26 isoforms play an important role herein by catalyzing the oxidation of RA. Much of previous literature regarding Cyp26 biology described its action on fetal development and carcinogenesis, however the role of Cyp26 in the context of intermediary metabolism is yet to be fully understood. We hypothesized that Cyp26a1 expression is regulated following feeding/fasting cycle, based on the facts that: (1) vitamin A homeostasis is closely related to metabolism; (2) Cyp26a1 is a key enzyme regulating atRA level; (3) liver is the primary organ where CYP26A1 is expressed in humans. First, we measured Cyp26a1 expression in liver collected from male and female C57Bl/6J mice that were divided into 16 hrs fasted and 6 hrs re-fed groups and found that Cyp26a1 expression was higher in livers of re-fed compared to the fasted group from both sexes. To further investigate mechanisms, HepG2 cells were treated with key feeding/fasting signaling molecules following serum-starvation for 18 hrs. Dexamethasone, cortisol and glucagon significantly repressed atRA-induced CYP26A1 expression in dose- and time-dependent manners, whereas insulin had no effect. No additional or synergistic effect between glucocorticoids and glucagon was observed. These findings raise an important question on mechanism by which glucagon or glucocorticoids down-regulate CYP26A1 expression. We currently are exploring these mechanisms.
Interested students will have an excellent opportunity for hands-on training in basic techniques in cell culture, molecular biology, as well as mouse colony management. Students will assist a senior lab member in mouse colony maintenance, tissue collection, gene expression assay, and western blot. Depending on students’ ability to work at the bench, student will have opportunity to have hands-on experience in more advanced techniques including molecular cloning, ChIP, and genetic modification such as CRISPR. Students will work under close supervision of the senior lab member, and will be expected to keep a detailed lab journal regarding conducted experiments, read relevant research articles and attend lab discussions. Students will be involved in data collection and analysis.
Applicant should be familiar with fundamentals of chemistry, biochemistry, molecular biology and genetics, and show a strong interest in metabolism research. Previous experience in biology and chemistry laboratory in classroom settings is required. Ability to follow detailed protocols, pay close attention to experimental details, and learn quickly is necessary. Critical thinking and independent work is fostered and encouraged in our laboratory. Ability to work with live animals is desirable, and comprehensive training will be provided.