Academic & Professional Updates
Advisor: Dr. Daniel Liebler
While at the University of Arizona, my project was to use mass spectrometry to analyze the mechanism of activation of Keap-Nrf2 singaling pathway induced by electrophiles. Nrf2 is the transcription factor that regulates the expression of Phase II enzymes so that cells can defend themselves against electrophiles. Keap1 binds to Nrf2 as adaptor protein for the ubiquitination and degradation of Nrf2. When electrophilic inducer bound to specific cystein residues of Keap1, Nrf2 is stabilized and activated. With some biotin-taged electrophiles and mass spectrometry, we mapped the adduct sites formed on keap1. We found when electrophiles attack the central linker domain of keap1, ubiquitination is transferred from Nrf2 to Keap1 so that Nrf2 is stabilized and activated.
In addition, we studied a cancer chemopreventive agent sulforaphane, which is isolated from cruciferous vegetables, such as broccoli and cauliflower. We found sulforaphane can also form adduct on Keap1 and activate Nrf2, but using a different mechanism. Since sulforaphane adducts on cysteine residue are labile and with standart sample preparation procedure, not adduct can be mapped with mass spectrometry. We worked on the methodology and finally we come up with a new protocol to characterize labile adducts.
I am currently working at Tyr Pharma Inc. using Mass Spectrometry to analyzed protein therapeutics, including protein degradation, oxidation, disulfide bond formation, pegylation and deamination.