What's Going On Here?? A quick summary of my lab's work

The Iwasaki Lab at Yale is an immunobiology lab, but the project I’m working on has far-reaching applications. My mentor, Daniel Kim, is a PhD student investigating the hypothesis that Vitamin B12 and Folic Acid are biologically relevant antagonists for the Aryl Hydrocarbon Receptor.

Okay- what do any of those words mean? The Aryl Hydrocarbon Receptor (AhR) is a protein found in cells that controls the rate at which certain segments of DNA are transcribed into RNA. AhR agonists increase the transcription rate, and AhR antagonists decrease the transcription rate of the target genes. A LOT of AhR agonists are known, but not many antagonists. This brings up the question- if there are so many agonists and no antagonists to balance them, why aren’t we always suffering from AhR over-expression? The symptoms of over-expression include anemia, birth defects, skin pigmentation, peripheral neuropathy, and immunodeficiency.

Vitamin B12 is an essential vitamin with two known tasks: DNA creation and fatty acid oxidation. Both of these tasks are driven by one part of the Vitamin B12 molecule, but the other main part- which just happens to have a piece that could potentially bind to AhR- isn’t well understood. Vitamin B12 deficiency has a long list of symptoms, including anemia, birth defects, skin pigmentation, peripheral neuropathy, and immunodeficiency. Sound familiar?? It’s the same symptom list as AhR over-expression. Although these symptoms are well-known, however, it isn’t understood WHY or HOW Vitamin B12 deficiency leads to these effects.

So the hypothesis is that Vitamin B12 (and Folic Acid) are actually AhR antagonists. In order to test this hypothesis, the lab is running both in vivo (in living mice) and in vitro (in human cell lines in the lab) experiments. The in vivo experiments with the mice are aimed at determining whether the addition of Vitamin B12 and it’s separate components can rescue mice from the negative symptoms of AhR over-expression. The in vitro experiments are able to analyze the expression of AhR in the presence of an agonist plus Vitamin B12 and its components.

Woah! That was a lot of science. And trust me- it gets a lot more complicated! What’s even cooler about these experiments is that they have the potential to completely change the way we think about Vitamin B12, Folic Acid, and AhR. It’s possible that in the future, textbooks will be totally re-written to accommodate these ideas and results! If you want to learn more about these experiments, reach out to me. There’s a lot more I didn’t cover here that is absolutely fascinating, and I’m always looking to share information!